Malevolent Design - The Sneak Tactics of Toxoplasma gondii

Toxoplasma gondii.

Image by Michael Holmes

Toxoplasma gondii parasite uses unconventional method to make proteins for evasion of drug treatment

Here we are with yet another example of an organism that, if there is a designer behind it, that designer can only be described as malevolent and determined to maximise the suffering and misery in the world.

It is, of course, another example of a nasty little parasite which, if you subscribe to the creationist view that complexity 'proves' design, has been designed to ensure we are as vulnerable to is as possible by helping it evade the immune system and other mechanisms, supposedly designed by the same designer god to protect us from the parasites it designs to harm us.

This example is the parasite Toxoplasma gondii, which is notorious for manipulating its natural victims, which are felines and their prey species. For example, mice infected with T. gondii lose their fear of cats so they get eten and the parasite gets into its primary host; infected chimpanzees develop a liking for the smell of leopard urine.

Humans are not the natural secondary host, but the parasite readily infects us as we catch it from cats. It is thought that about one third of humans are infected. Once infected it is impossible to get rid of from the body because, even if antibodies are produced by our immune system, the parasites go into a dormant state as cysts which can form in any organs of the body, including the brain.

Toxoplasma gondii, it's evolution and its pathology in humans. Toxoplasma gondii: Overview, Evolution, and Pathology in Humans

Toxoplasma gondii is a protozoan parasite that infects warm-blooded animals, including humans, but primarily completes its life cycle in felines. It is a member of the phylum Apicomplexa, which includes other parasitic organisms such as Plasmodium (responsible for malaria). The parasite is notorious for its widespread prevalence and potential to cause severe disease in immunocompromised individuals and during pregnancy.

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Evolutionary History

Toxoplasma gondii evolved from a common ancestor shared with other apicomplexans. Its evolutionary journey highlights adaptations for survival in both definitive (cat) and intermediate (other animals) hosts.

1. Apicomplexan Origin:
   • The phylum likely evolved from free-living photosynthetic algae.
   • The apicoplast, a remnant plastid, is a key organelle in T. gondii, crucial for fatty acid synthesis and other metabolic functions.
2. Host Adaptations:
   • Unlike its relatives with narrow host ranges, T. gondii evolved to infect a vast array of intermediate hosts. This adaptability is attributed to its ability to form hardy oocysts that can survive in the environment and tissue cysts that persist in hosts.
3. Clonal Lineages:
   • Population studies show three predominant clonal lineages (Types I, II, III), which emerged around 10,000 years ago, likely through a genetic bottleneck. These lineages exhibit differences in virulence and geographic distribution.

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Lifecycle

1. Sexual Stage:
   • Occurs only in the intestines of felines, the definitive host. Cats excrete oocysts in their faeces.
2. Oocysts:
   • Environmentally resilient and infectious after sporulation, oocysts can contaminate food, water, and soil.
3. Intermediate Hosts:
   • Oocysts are ingested by other animals (e.g., rodents, birds, and humans). The parasite then forms tachyzoites (rapidly dividing forms) and bradyzoites (slowly dividing cyst forms) in tissues like the brain and muscles.
4. Transmission to Cats:
   • Cats are infected when they eat intermediate hosts harbouring tissue cysts, perpetuating the lifecycle.

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Pathology in Humans

Humans typically acquire T. gondii through undercooked meat, contaminated water, or contact with infected cat faeces. Most infections are asymptomatic, but in certain populations, the parasite can cause significant disease.

1. Acute Toxoplasmosis:
   • Symptoms: Flu-like symptoms (fever, swollen lymph nodes, fatigue).
   • Immune response usually controls the infection, leading to cyst formation.
2. Latent Infection:
   • Tissue cysts persist, primarily in the brain and muscles, remaining dormant unless the immune system is compromised.
3. Immunocompromised Individuals:
   • Reactivation of latent infection can cause life-threatening conditions, such as toxoplasmic encephalitis, especially in individuals with HIV/AIDS or undergoing chemotherapy.
4. Congenital Toxoplasmosis:
   • If a woman acquires the infection during pregnancy, the parasite can cross the placenta, causing miscarriage, stillbirth, or severe congenital abnormalities (e.g., hydrocephalus, blindness, mental impairment).
5. Neurological and Behavioural Effects:
   • Emerging research suggests T. gondii might influence behaviour and mental health. It has been associated with altered risk-taking, neuropsychiatric disorders like schizophrenia, and changes in personality traits, though causation remains under investigation.

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Diagnosis and Treatment

1. Diagnosis:
   • Serological tests detect specific IgM and IgG antibodies.
   • PCR assays can identify parasite DNA, particularly in congenital infections.
2. Treatment:
   • Acute infections: Combination therapy with pyrimethamine and sulfadiazine, supplemented with folinic acid to prevent folate depletion.
   • Chronic latent infections usually do not require treatment unless reactivated.

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Control and Prevention

• Hygiene: Proper handwashing after handling soil, cats, or raw meat.
• Cooking Practices: Ensure meat is thoroughly cooked to destroy tissue cysts.
• Cat Care: Regular cleaning of litter trays and preventing cats from hunting can reduce environmental contamination.

Toxoplasma gondii remains a fascinating and medically important organism due to its evolutionary ingenuity, widespread distribution, and complex interactions with hosts, including humans.

How they do this is the subject of a paper in the Journal of Biological Chemistry by researchers from Indian University School of Medicine and a news release by Indiana University.

Toxoplasma gondii parasite uses unconventional method to make proteins for evasion of drug treatment

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A study by Indiana University School of Medicine researchers sheds new light on how Toxoplasma gondii parasites make the proteins they need to enter a dormant stage that allows them to escape drug treatment. It was recently published with special distinction in the Journal of Biological Chemistry.

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Toxoplasma gondii is a single-celled parasite that people catch from cat faeces, unwashed produce or undercooked meat. The parasite has infected up to one-third of the world's population, and after causing mild illness, it persists by entering a dormant phase housed in cysts throughout the body, including the brain.

Toxoplasma cysts have been linked to behaviour changes and neurological disorders like schizophrenia. They can also reactivate when the immune system is weakened, causing life-threatening organ damage. While drugs are available to put toxoplasmosis into remission, there is no way to clear the infection. A better understanding of how the parasite develops into cysts would help scientists find a cure.

Through years of collaborative work, IU School of Medicine Showalter Professors Bill Sullivan, PhD, and Ronald C. Wek, PhD, have shown that Toxoplasma forms cysts by altering which proteins are made. Proteins govern the fate of cells and are encoded by mRNAs.

But mRNAs can be present in cells without being made into protein. We've shown that Toxoplasma switches which mRNAs are made into protein when converting into cysts.

Professor William J. Sullivan Jr., Corresponding author
Department of Pharmacology & Toxicology
Indiana University School of Medicine
Indianapolis, Indiana, USA.

Lead Author Vishakha Dey, PhD, a postdoctoral fellow at the IU School of Medicine and a member of the Sullivan lab, examined the so-called leader sequences of genes named BFD1 and BFD2, both of which are necessary for Toxoplasma to form cysts.

mRNAs not only encode for protein, but they begin with a leader sequence that contains information on when that mRNA should be made into protein.

Dr. Vishakha Dey, lead author.

Department of Pharmacology & Toxicology
Indiana University School of Medicine
Indianapolis, Indiana, USA.

All mRNAs have a structure called a cap at the beginning of their leader sequence. Ribosomes, which convert mRNA into protein, bind to the cap and scan the leader until it finds the right code to begin making the protein.

What we found was that, during cyst formation, BFD2 is made into protein after ribosomes bind the cap and scan the leader, as expected. But BFD1 does not follow that convention. Its production does not rely on the mRNA cap like most other mRNAs.

Dr. Vishakha Dey.

The team further showed that BFD1 is made into protein only after BFD2 binds specific sites in the BFD1 mRNA leader sequence. Sullivan said this is a phenomenon called cap-independent translation, which is more commonly seen in viruses.

Finding it in a microbe that has cellular anatomy like our own was surprising. It speaks to how old this system of protein production is in cellular evolution. We're also excited because the players involved do not exist in human cells, which makes them good potential drug targets.

Professor William J. Sullivan Jr.

The Journal of Biological Chemistry featured the new study as an "Editor's Pick" paper, which represent a select group of the journal’s publications judged to be of exceptionally high quality and broad general interest to their readership.

This paper describes a mechanism by which a parasite that causes toxoplasmosis in humans can respond to stress and allow the parasite to thrive. The discovery of this mechanism provides a basis for treating these infections. Moreover, a similar mechanism is important in cancer, suggesting that it may be a therapeutic target for multiple human diseases.

Professor George N. DeMartino, PhD, associate editor of the Journal of Biological Chemistry
University of Texas Southwestern Medical Center.

Additional co-authors on the study include IU School of Medicine's Michael Holmes, PhD, and Matheus S. Bastos, PhD. The work was funded by the National Institutes of Health and the Showalter Foundation.

Translational control mechanisms modulate the microbial latency of eukaryotic pathogens, enabling them to evade immunity and drug treatments. The protozoan parasite Toxoplasma gondii persists in hosts by differentiating from proliferative tachyzoites to latent bradyzoites, which are housed inside tissue cysts. Transcriptional changes facilitating bradyzoite conversion are mediated by a Myb domain transcription factor called BFD1, whose mRNA is present in tachyzoites but not translated into protein until stress is applied to induce differentiation. We addressed the mechanisms by which translational control drives BFD1 synthesis in response to stress-induced parasite differentiation. Using biochemical and molecular approaches, we show that the 5′-leader of BFD1 mRNA is sufficient for preferential translation upon stress. The translational control of BFD1 mRNA is maintained when ribosome assembly near its 5′-cap is impaired by insertion of a 5′-proximal stem-loop and upon knockdown of the Toxoplasma cap-binding protein, eIF4E1. Moreover, we determined that a trans-acting RNA-binding protein called BFD2/ROCY1 is necessary for the cap-independent translation of BFD1 through its binding to the 5′-leader. Translation of BFD2 mRNA is also suggested to be preferentially induced under stress but by a cap-dependent mechanism. These results show that translational control and differentiation in Toxoplasma proceed through cap-independent mechanisms in addition to canonical cap-dependent translation. Our identification of cap-independent translation in protozoa underscores the antiquity of this mode of gene regulation in cellular evolution and its central role in stress-induced life-cycle events.

Abbreviations

AP2apetala-2BFD1Bradyzoite Formation Deficient-1BRBinding RegionCDSprotein-coding sequenceFLucfirefly luciferaseNLucNano luciferaseRLURelative Luciferase UnitsuORFsupstream open reading frames

Cellular adaptation and differentiation processes in response to cellular stresses are initiated by reprogramming of gene expression. A central feature of this reprogramming is the rapid lowering of global protein synthesis in favor of selective translation of a subset of mRNAs that include transcription factors that activate genes for stress remediation or differentiation (1, 2, 3). We have shown that this paradigm governs life cycle stage transitions in protozoan parasites that underlie transmission and pathogenesis of infectious disease (3, 4, 5). The study of translational control in these early-branching eukaryotes not only promises to reveal potential novel drug targets but also sheds important mechanistic insights into the evolutionary origins of these regulatory processes (6, 7, 8).

Toxoplasma gondii is an obligate intracellular parasite of warm-blooded animals that causes opportunistic disease in humans. Upon ingestion, the parasites transform into a rapidly replicative stage (tachyzoite) that disseminates throughout the host body before converting into a quiescent stage (bradyzoite) housed in tissue cysts that can be sustained for the life of the host. Tissue cysts are a major route of transmission through the consumption of raw or undercooked meat (9). Reactivation of bradyzoites can occur when patients become immunocompromised, producing life-threatening damage to critical areas where tissue cysts typically reside, such as the brain, heart, and skeletal muscle (10). Current treatments of toxoplasmosis only target replicating tachyzoites and do not appear to exert appreciable activity against the formation or viability of tissue cysts (11). The formation of latent tissue cysts allows Toxoplasma to persist in its host and prevents a radical cure of this infection.

Given the importance of bradyzoites in driving parasite transmission and chronic disease, much research is aimed at understanding the molecular mechanisms orchestrating the conversion between tachyzoites and bradyzoites (12). Differentiation between life cycle stages requires the reprogramming of gene expression, while chromatin remodeling machinery and several apetala-2 (AP2) factors have been shown to contribute to the transcription of bradyzoite-inducing genes (13). Recently, Lourido and colleagues identified a “master regulator” transcription factor termed BFD1 (Bradyzoite Formation Deficient-1) that is necessary and sufficient for bradyzoite formation (14).

BFD1 is a SANT/Myb-like DNA-binding protein whose mRNA is present in tachyzoites but not translated until parasites are exposed to a bradyzoite-induction stress (14). We previously suggested with polysome profiling that BFD1 mRNA is preferentially translated when tachyzoites are subjected to a stress that induces bradyzoite differentiation (15). These studies indicate that expression of BFD1 protein is predominantly regulated by translational control and the elevated levels of BFD1 are sufficient to confer transcription events directing cyst formation. Consistent with this idea, the 5′-leader sequence of BFD1 mRNA is about 2.7 kb in length, harboring multiple predicted upstream open reading frames (uORFs), which are known in other model systems to regulate start codon selection and translation efficiency of the protein-coding sequence (CDS) (16). Moreover, a CCCH-type zinc finger mRNA-binding protein called BFD2 (also referred to as ROCY1) has recently been described that is suggested to direct the stress-dependent translation of BFD1 (17, 18).

Bulk cellular translation begins with eIF4F association with the 5′-cap of mRNAs through its eIF4E subunit, which then recruits the ribosomal preinitiation complex that proceeds to scan the 5′-leader for an optimal start codon (19). This cap-dependent translation can be modulated by uORFs that can be bypassed by scanning ribosomes or allow for re-initiation for efficient CDS translation (20). Cap-independent mechanisms have also been described, most commonly among viruses and less frequently for cellular mRNAs (21, 22, 23). Translation that can occur independent of eIF4E cap association and the subsequent ribosome scanning typically involves direct entry of ribosomes onto the 5′-leader sequence by secondary structures that interface with trans-acting proteins to recruit initiating ribosomes (22, 23).

In this study, we addressed the mechanisms of preferential translation of BFD1 during stress-induced bradyzoite differentiation. Utilizing luciferase reporter assays and genetically modified Toxoplasma parasites, we show that BFD1 translation can occur through a cap-independent mechanism that involves BFD2 binding to the 5′-leader sequence. By comparison, preferential translation of BFD2 during stress occurs by cap-dependent processes. Our results represent the first evidence of cap-independent translation in protozoa, suggesting that it is an ancient mechanism of gene regulation present in early-branching eukaryotes and is critical for directing differentiation in the Toxoplasma life cycle.

We can, of course, dismiss Michael J. Behe's biologically nonsensical excuse of 'devolution' from some presupposed initial perfection because any change which makes an organism better at producing descendants is classically evolutionary and it take mental gymnastics to a new hight of absurdity to believe that something better is less perfect than what preceded it.

So, as always, what creationists need to find the moral and intellectual courage to address is the question of evil and why their supposed creator creates these nasty little parasites that are responsible for so much suffering and misery in the world. Are they just the result of incompetent design or the malevolent design of an omnipotent, omniscient designer? Or are they the result of a mindless natural process?

Malevolent Design - How Malaria Is Being Redesigned to Keep On Killing Children

Photomicrograph of a blood smear contains a macro- and microgametocyte of the Plasmodium falciparum parasite

Photo Credit: CDC/Dr. Mae Melvin - This media comes from the Centers for Disease Control and Prevention's Public Health Image Library (PHIL) #2704, Public Domain, Link

Study uncovers first evidence of resistance to standard malaria treatment in African children with severe malaria

In another twist of the arms race with human medical science Plasmodium falciparum, the malevolently designed parasite that causes malaria and kills hundreds of thousands of children a year, mostly in Africa, has developed resistance to Artemisinin. Scientists were already aware that resistance had arisen in cases of uncomplicated malaria, but this is the first such incidence of resistance in the more severe form of the disease.

Indiana University School of Medicine researchers, in collaboration with colleagues at Makerere University in Uganda have discovered a case of complicated malaria in a child in Uganda.

Mallevolent Design - How Salmonella Sneaks Past Our Defences To Make Us Sick

Salmonella infects the small intestine and alters the colon environment

Intestinal lumen

New study shows how salmonella tricks gut defenses to cause infection

There is a simple paradox at the heart of creationism that I have never even seen an attempt to resolve. It all comes from two beliefs: there is only one designer god capable of designing living organisms and that designer god designed us complete with our immune system with which we can attempt to resist attack by pathogens, and that pathogens are not the work of this design, but are the result of 'genetic entropy' and 'devolution' since Adam & Eve let 'sin' into the world. The fact that Michael J. Behe, who invented that excuse, has let slip that ID Creationism is Bible literalism in a lab coat seems to be lost on his followers who still dutifully insist that it is a scientific alternative to evolution and should be taught in school science class (presumably now with the tale of Adam & Eve taught as real history and 'sin' as a real force in science).

The paradox is, did the designer god give Adam & Eve an immune system, or did it design an upgrade when 'sin' allowed pathogens to exist? If the former, it was anticipating and planning for the so-called 'fall'; if the latter, it lacked foresight so is not omniscient.

But however creationists resolve this paradox they still have to explain why the 'intelligently designed' immune system doesn't work very well and why whatever is designing pathogens seems to be able to overcome it.

The nonsense about 'sin', 'the fall', etc., is trivially easy to refute because any improvement in a parasite's ability to parasitise its host can't possibly be regarded as a devolution from some assumed initial perfection because an improvement can't be worse that what it's an improvement on. The whole nonsense of 'devolution' is biological gobbledygook, intelligently designed to appeal to scientifically illiterate simpletons who want to fit the Bible superstition somewhere in the reasoning without bothering too much about the logic or the biology.

So, the paradox boils down to why an intelligent designer would be having an arms race with itself so the parasites it creates can continue to parasitise the victims it creates complete with their immune system it created to stop them. Creationists normally flee in terror at the mere mention of arms races, which is why you'll never see them discussed in the cult literature apart from where pathogens are waved aside as 'caused by sin', blah, blah, blah...
So, it would be refreshing indeed to see a genuine attempt by an intelligent design creationist try to give some rational explanation, and hopefully without giving away the fact that ID creationism is merely Christian fundamentalism in disguise, for the discovery by a new UC Davis Health study that shows how the Salmonella bacteria, a major cause of food poisoning, can invade the gut even when protective bacteria are present.

As an added embarrassment for creationists, Salmonella is closely related to Escherichia coli (E.coli) that they usually cite Michael J. Behe as 'proving' it must have been designed by their god because its flagellum is 'irreducibly complex'.

First a little AI background information about Salmonella, where it came from and what it does to us:

Tell me all about Salmonella, please. Salmonella is a genus of bacteria that is commonly associated with foodborne illnesses in humans and animals. These bacteria are known for causing a range of conditions, from mild gastroenteritis to more severe diseases like typhoid fever. Here's an overview of Salmonella:

1. What is Salmonella?
   Salmonella are rod-shaped, Gram-negative bacteria belonging to the family Enterobacteriaceae. They are facultative anaerobes, meaning they can grow in both oxygen-rich and oxygen-poor environments.
   
2. Types of Salmonella
   Salmonella is classified into two broad categories based on the diseases they cause:
   
   
   1. Non-typhoidal Salmonella (NTS):
      • Causes salmonellosis, a common form of food poisoning.
      • Found in many animals, including poultry, cattle, reptiles, and amphibians.
      • Symptoms include diarrhea, fever, abdominal cramps, and vomiting.
   2. Typhoidal Salmonella:
      • Includes Salmonella Typhi and Salmonella Paratyphi, which cause typhoid and paratyphoid fever, respectively.
      • These infections are severe, systemic diseases primarily transmitted through contaminated water or food.
3. How is Salmonella Transmitted?
   
   • Foodborne: Consuming undercooked or contaminated meat (especially poultry), eggs, or dairy products.
   • Waterborne: Drinking contaminated water.
   • Contact: Handling animals or surfaces contaminated with Salmonella, such as pet reptiles or farm animals.
   • Person-to-Person: Rare but possible in cases of poor hygiene, especially among caregivers.
4. Symptoms of Salmonella Infection
   The symptoms vary based on the type:
   • Salmonellosis (non-typhoidal): Appears 6-72 hours after exposure; lasts 4-7 days.
     
     • Diarrhea
     • Fever
     • Abdominal cramps
     • Nausea and vomiting
   • Typhoid Fever: Develops gradually over 1-2 weeks.
     
     • High fever
     • Weakness
     • Abdominal pain
     • Rose-colored spots on the skin
     • Constipation or diarrhea
5. Risk Groups
   
   • Infants, young children, and the elderly.
   • People with weakened immune systems, such as those with HIV or undergoing chemotherapy.
   • Travelers to regions with poor sanitation.
6. Diagnosis
   
   • Laboratory Testing: Stool, blood, or urine samples are tested for the presence of Salmonella.
   • Serotyping: Identifies specific Salmonella strains, useful for outbreaks and epidemiological studies.
7. Treatment
   
   • Non-typhoidal Salmonella: Often self-limiting; hydration is crucial. Antibiotics are usually unnecessary unless the infection spreads beyond the intestines.
   • Typhoidal Salmonella: Requires prompt antibiotic treatment, such as ciprofloxacin or azithromycin. Severe cases may require hospitalization.
8. Prevention
   
   1. Food Safety:
      • Cook meat and eggs thoroughly.
      • Avoid cross-contamination between raw and cooked foods.
      • Wash fruits and vegetables well.
      • Store food at proper temperatures.
   2. Hygiene:
      
      • Wash hands frequently, especially after handling animals or raw foods.
      • Sanitize surfaces and utensils.
   3. Vaccination:
      • Vaccines are available for Salmonella Typhi for travelers to high-risk areas.
   4. Pet Precautions:
      • Avoid contact with reptiles or amphibians, especially for children under five.
9. Global Impact
   • Non-typhoidal Salmonella: A leading cause of foodborne illnesses worldwide.
   • Typhoid Fever: Endemic in many developing countries, with poor sanitation contributing to its prevalence.

Interesting Facts

• Salmonella is named after American scientist Daniel Elmer Salmon, though it was first discovered by Theobald Smith in 1885.
• These bacteria can survive on dry surfaces for weeks and in water for months.
  

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What is known about the evolutionary origins of the genus and their relationship to other genera?

The genus Salmonella has a fascinating evolutionary history that reflects its adaptation to a wide range of hosts and ecological niches. Here's an overview of what is known about its evolutionary origins and relationships with other genera:

1. Evolutionary Origins
   • Family and Order:
     • Salmonella belongs to the family Enterobacteriaceae and the order Enterobacterales. This group includes other genera such as Escherichia, Klebsiella, Yersinia, and Shigella.
     • These bacteria are believed to have a common ancestor that lived in the intestinal tracts of primitive animals hundreds of millions of years ago.
   • Divergence from Common Ancestor:
     • Genomic analyses suggest that Salmonella diverged from its closest relative, Escherichia coli, approximately 100–150 million years ago. This divergence was likely driven by adaptation to different ecological niches and hosts.
     • Salmonella has specialized in both intestinal and systemic infections, while E. coli primarily remained a commensal organism with occasional pathogenic strains.
2. Genomic Evolution
   • Horizontal Gene Transfer (HGT):
     • A significant driver of Salmonella's evolution has been the acquisition of genes through horizontal gene transfer. This process introduced:
       • Virulence genes (e.g., pathogenicity islands).
       • Antibiotic resistance genes.
     • These acquisitions allowed Salmonella to colonize new hosts and environments.
   • Pathogenicity Islands:
     • The genome of Salmonella contains specialized regions called Salmonella Pathogenicity Islands (SPIs) that encode genes crucial for infection.
     • SPIs are thought to have been acquired from other bacteria through HGT and are absent in its close relatives, such as E. coli.
   • Adaptive Evolution:
     • Salmonella has developed mechanisms to survive harsh conditions, such as the acidic environment of the stomach or macrophage phagosomes. Genes encoding acid resistance and intracellular survival are key to this adaptation.
3. Speciation and Lineage Divergence
   
   • The genus Salmonella is divided into two main species:
     1. Salmonella enterica: The most diverse and widespread species, with six subspecies and over 2,500 serovars.
     2. Salmonella bongori: Found primarily in cold-blooded animals, such as reptiles.
   • Host Adaptation:
     • Salmonella enterica has evolved to infect a wide range of warm-blooded and cold-blooded hosts, whereas S. bongori remains restricted to reptiles.
     • Within S. enterica, specific serovars have adapted to particular hosts (e.g., S. Typhi for humans and S. Dublin for cattle).
4. Relationship to Other Genera
   • Closest Relatives:
     • Escherichia coli: Shares a common ancestor with Salmonella. The two genera are highly similar at the genomic level but differ significantly in pathogenicity and host adaptation.
     • Shigella: Genetically very similar to E. coli but evolved independently to cause invasive infections.
   • Phylogenetic Placement:
     • Within Enterobacteriaceae, Salmonella is part of a subgroup that includes pathogens like Shigella and Yersinia.
     • Comparative genomics shows that Salmonella diverged from E. coli after acquiring genes enabling systemic infection and survival in macrophages.
5. Ecological and Evolutionary Pressures
   • Host-Pathogen Interactions:
     • The evolutionary success of Salmonella is linked to its ability to exploit host defenses. For example, genes enabling intracellular survival have allowed it to persist within macrophages.
   • Environmental Reservoirs:
     • While primarily associated with animals, Salmonella can survive in environmental reservoirs like water and soil. This versatility has helped it spread globally.
6. Evolutionary Insights from Genomics
   • Advances in genomic sequencing have clarified Salmonella's evolutionary trajectory:
   • Core Genome: Highly conserved genes related to metabolism and cell structure.
   • Accessory Genome: Includes mobile genetic elements like plasmids, transposons, and bacteriophages that contribute to virulence and antibiotic resistance.
7. Molecular Clock Studies:
   • Analysis of mutation rates suggests that Salmonella continues to evolve rapidly, especially in response to human interventions like antibiotics.

Key Takeaways:

• Salmonella evolved from a common ancestor with E. coli but adapted to systemic infections through gene acquisition and environmental pressures.
• Its genomic flexibility and ability to colonize diverse hosts have been critical to its evolutionary success.
• Relationships with other genera, like Escherichia and Shigella, reveal a shared evolutionary history with divergence driven by ecological specialization.

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Is there much evidence of host-specificity?

Yes, there is considerable evidence of host specificity in Salmonella, with some serovars adapting to infect specific hosts more effectively than others. However, the extent of host specificity varies among Salmonella serovars and is influenced by their evolutionary adaptations and ecological niches. Here's a breakdown:

1. Host-Specific vs. Broad-Host-Range Serovars
   
   • Host-Specific Serovars:
     • These serovars are restricted to specific hosts and often cause severe, systemic infections in their target species.
       • Salmonella Typhi: Human-specific, causing typhoid fever.
       • Salmonella Paratyphi: Human-specific, causing paratyphoid fever.
       • Salmonella Dublin: Primarily infects cattle but can occasionally infect humans, usually causing severe disease.
       • Salmonella Choleraesuis: Adapted to pigs and can cause systemic infections in swine.
   • Broad-Host-Range Serovars:
     • These serovars infect a wide range of hosts and typically cause gastroenteritis.
       • Salmonella Enteritidis: A leading cause of foodborne illness in humans, associated with poultry and eggs but can infect other animals.
       • Salmonella Typhimurium: Infects a wide variety of mammals, birds, and reptiles, and is a common cause of foodborne illness.
2. Mechanisms of Host Specificity
   The host specificity of Salmonella serovars is influenced by several genetic and molecular factors:
   • Pathogenicity Islands (SPIs):
     • Salmonella Pathogenicity Islands (SPIs) encode virulence factors like Type III Secretion Systems (T3SSs) that allow the bacteria to invade and survive in host cells.
     • Differences in SPI genes contribute to host specificity. For instance:
       • S. Typhi and S. Paratyphi have unique virulence factors (e.g., Vi antigen) that help evade the human immune system.
       • S. Dublin has genes that enhance its ability to persist in cattle.
   • Adhesins and Surface Proteins:
     • Host specificity is often mediated by adhesins, which enable the bacteria to bind to specific host tissues.
     • For example, S. Typhi expresses fimbriae and adhesins that preferentially bind to receptors found in human intestinal epithelial cells.
   • Immune Evasion:
     • Host-specific serovars have evolved mechanisms to evade or modulate the immune responses of their target hosts.
       • S. Typhi produces proteins that suppress human immune responses, facilitating systemic infection.
   • Metabolic Adaptations:
     • Host-specific serovars often exhibit metabolic pathways tailored to the nutrient environment of their host. For example, some serovars can utilize host-specific compounds as energy sources.
3. Evidence from Genomic Studies
   Genomic studies have revealed key differences between host-specific and broad-host-range serovars:
   
   • Unique Genes:
     • Host-specific serovars often have genes not found in broad-host-range strains. These genes may encode virulence factors, metabolic enzymes, or regulatory proteins specific to their host environment.
   • Pseudogenes:
     • Host-restricted serovars like S. Typhi often have many pseudogenes—nonfunctional remnants of genes. This suggests they have lost functions unnecessary for survival in their specific host, leading to a narrowing of their ecological niche.
   • Phylogenetic Insights:
     • Phylogenetic analysis shows that host-restricted serovars tend to form distinct clades, reflecting their adaptation to specific hosts.
4. Experimental Evidence
   • Animal Models:
     • Studies using animal models have demonstrated the inability of host-specific serovars to infect non-native hosts effectively.
       • S. Typhi does not cause disease in mice or cattle without genetic modification.
       • S. Dublin causes systemic disease in cattle but only sporadic, severe infections in humans.
   • Natural Observations:
     • Epidemiological data show strong associations between certain serovars and specific hosts. For example:
       • S. gallinarum and S. pullorum are highly adapted to poultry, causing fowl typhoid and pullorum disease, respectively.
5. Exceptions and Spillover Events
   
   While some Salmonella serovars are highly host-specific, spillover events can occur:
   
   • Broad-host-range serovars like S. Typhimurium can infect a wide variety of species, often leading to zoonotic transmission to humans.
   • Host-specific serovars can occasionally infect non-native hosts, sometimes leading to severe disease. For instance:
     • S. Dublin can cause life-threatening bacteremia in humans, particularly in immunocompromised individuals.
6. Implications for Public Health and Veterinary Medicine
   
   Understanding host specificity is crucial for controlling Salmonella infections:
   
   • Zoonotic Risks: Broad-host-range serovars pose significant zoonotic threats, especially in foodborne outbreaks.
   • Vaccination and Control Strategies: Vaccines and interventions can be tailored to target specific serovars in their primary hosts (e.g., poultry vaccines against S. Enteritidis).

Conclusion
Host specificity in Salmonella reflects a complex interplay of genetic, molecular, and ecological factors. While some serovars are highly specialized, others maintain the flexibility to infect a broad range of hosts, contributing to their global prevalence and significance as pathogens.

What the UC Davis Health study, led by Professor Andreas Bäumler of the Department of Medical Microbiology and Immunology found is the subject of a paper in Proceeding of The National Academy of Science (PNAS) and a UC Davis press release by Nadine A Yehya:

New study shows how salmonella tricks gut defenses to cause infection

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(SACRAMENTO) A new UC Davis Health study has uncovered how Salmonella bacteria, a major cause of food poisoning, can invade the gut even when protective bacteria are present. The research, published in the Proceedings of the National Academy of Sciences, explains how the pathogen tricks the gut environment to escape the body's natural defenses.

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The digestive system is home to trillions of bacteria, many of which produce short-chain fatty acids (SCFAs) that help fight harmful pathogens. But Salmonella manages to grow and spread in the gut, even though these protective compounds are present. The study asks: How does Salmonella get around this defense?

We knew that Salmonella invades the small intestine, although it is not its primary site of replication. The colon is.

Professor Andreas Bäumler, lead author
Department of Medical Microbiology and Immunology
School of Medicine
University of California at Davis, Davis, CA, USA.

Bäumler and his team discovered that the answer lies in how the pathogen changes the gut’s nutrient balance. When Salmonella enters the small intestine, it causes inflammation in the gut lining and disrupts the normal absorption of amino acids from food. This creates an imbalance in nutrients in the gut.

The imbalance gives Salmonella the resources it needs to survive and multiply in the large intestine (colon), where beneficial bacteria usually curb its growth. The study showed that salmonella causes inflammation in the small intestine in order to derive nutrients that fuel its replication in the colon.

Salmonella alters gut nutrient environment to survive

Using a mouse model, the team looked closely at how Salmonella changed the chemical makeup of the gut. They traced amino acid absorption in the small and large intestines.

They found that in mice that were infected with Salmonella, there was less absorption of amino acids into the blood. In fact, two amino acids, lysine and ornithine, became more abundant in the gut after infection. These amino acids helped Salmonella survive by preventing the growth-inhibiting effects of SCFAs. They did this by restoring Salmonella’s acidity (pH) balance, allowing the pathogen to bypass the microbiota’s defenses.

Our findings show that Salmonella has a clever way of changing the gut’s nutrient environment to its advantage. By making it harder for the body to absorb amino acids in the ileum, Salmonella creates a more favorable environment for itself in the large intestine.

Professor Andreas Bäumler.

In the study, the team showed that Salmonella uses its own virulence factors (disease causing molecules) to activate enzymes that break down key amino acids like lysine. This helps the pathogen avoid the SCFAs’ protective effects and grow more easily in the gut.

New insights could lead to better gut infection treatments

The new insights potentially explain how the gut environment changes during inflammatory bowel disorders , such as Crohn's disease and ulcerative colitis, and could lead to better treatments for gut infections. By understanding how Salmonella changes the gut environment, researchers hope to develop new ways to protect the gut microbiota and prevent these infections.

This research uses a more holistic approach to studying gut health. It not only gives us a better understanding of how Salmonella works, but also highlights the importance of maintaining a healthy gut microbiota. Our findings could lead to new treatments that help support the microbiota during infection. By learning how a pathogen manipulates the host’s system, we can uncover ways to boost the host’s natural defenses.

Dr. Lauren Radlinski, first author.
Department of Medical Microbiology and Immunology
School of Medicine
University of California at Davis, Davis, CA, USA.

The study’s results could inspire future treatments, including probiotics or dietary plans designed to strengthen the body’s natural defenses against harmful pathogens.

Coauthors of the study are Andrew Rogers, Lalita Bechtold, Hugo Masson, Henry Nguyen, Anaïs B. Larabi, Connor Tiffany, Thaynara Parente de Carvalho and Renée Tsolis of UC Davis.

Significance
The microbiota protects the host from microorganisms that cause disease in unprotected or immunocompromised individuals. Enteric pathogens such as Salmonella enterica serovar (S.) Typhimurium are adept at circumventing and weakening these protections and in doing so render the host susceptible to infection. Here, we identify a strategy by which S. Typhimurium uses its virulence factors to manipulate the host environment in the small intestine to trigger downstream changes in the environment of the large intestine that enable the pathogen to overcome microbiota-mediated defenses. The more general implications of our work are that ileitis-induced malabsorption causes downstream changes in microbial growth conditions in the large intestine, which can trigger compositional changes.

Abstract
The gut microbiota produces high concentrations of antimicrobial short-chain fatty acids (SCFAs) that restrict the growth of invading microorganisms. The enteric pathogen Salmonella enterica serovar (S.) Typhimurium triggers inflammation in the large intestine to ultimately reduce microbiota density and bloom, but it is unclear how the pathogen gains a foothold in the homeostatic gut when SCFA-producing commensals are abundant. Here, we show that S. Typhimurium invasion of the ileal mucosa triggers malabsorption of dietary amino acids to produce downstream changes in nutrient availability in the large intestine. In gnotobiotic mice engrafted with a community of 17 human Clostridia isolates, S. Typhimurium virulence factors triggered marked changes in the cecal metabolome, including an elevated abundance of amino acids. In an ex vivo fecal culture model, we found that two of these amino acids, lysine and ornithine, countered SCFA-mediated growth inhibition by restoring S. Typhimurium pH homeostasis through the inducible amino acid decarboxylases CadA and SpeF, respectively. In a mouse model of gastrointestinal infection, S. Typhimurium CadA activity depleted dietary lysine to promote cecal ecosystem invasion in the presence of an intact microbiota. From these findings, we conclude that virulence factor–induced malabsorption of dietary amino acids in the small intestine changes the nutritional environment of the large intestine to provide S. Typhimurium with resources needed to counter growth inhibition by microbiota-derived SCFAs.

The gut microbiota is a critical frontline barrier that precludes the expansion of invading microorganisms through the production of antimicrobial compounds and the depletion of essential nutrients (1). During homeostasis, obligately anaerobic bacteria dominate the microbiota of the large intestine and ferment unabsorbed carbohydrates to produce high luminal concentrations of the short-chain fatty acids (SCFAs) acetate, propionate, and butyrate. These SCFAs are weak acids that become protonated in mildly acidic environments (HAc), such as the lumen of the colon (pH 5.7 to 6.2) (2), as the pH approaches the respective negative base-10 logarithm of the acid dissociation constant (pKa) for each molecule (~pH 4.7). Protonated SCFA are membrane permeable, but exposure to a more neutral pH in the cytosol (pH 7.2 to 7.8) (3–5) results in their dissociation into the salt and a proton (Ac⁻ + H⁺). The consequent acidification of the bacterial cytosol results in growth inhibition and serves as a canonical, nonspecific defense mechanism against invading enteric pathogens such as Salmonella enterica serovar Typhimurium (S. Typhimurium) (3, 6–8).

S. Typhimurium uses its virulence factors, two type III secretion systems (T3SS-1 and T3SS-2) (9, 10) encoded by Salmonella pathogenicity island (SPI)1 and SPI2 (11, 12), respectively, to break colonization resistance through mechanisms that are not fully resolved (13, 14). T3SS-1 and T3SS-2 trigger intestinal inflammation (15–17), which boosts growth of S. Typhimurium by increasing the availability of host-derived respiratory electron acceptors, including tetrathionate (18), nitrate (19, 20), and oxygen (21). In addition, aspartate is liberated when phagocyte-derived reactive oxygen species lyse luminal bacteria (22), which fuels growth of S. Typhimurium through fumarate respiration (23). Tetrathionate respiration has been shown to promote growth of S. Typhimurium in the lumen of the murine cecum by utilizing ethanolamine (24), which is generated when taurine liberated during deconjugation of bile acids is used as an electron acceptor by Deltaproteobacteria. Oxygen and nitrate enable the pathogen to utilize host-derived lactate (25) or 1,2-propanediol (26), a microbiota-derived fermentation product of pentoses. However, growth during in vitro culture under conditions that mimic the cecal environment suggests that high concentrations of SCFAs and the acidic environment of the cecum counter the competitive edge that oxygen and nitrate respiration confer upon the pathogen (27). These data suggest that S. Typhimurium virulence factors act on the host to generate yet unidentified resources that enable the pathogen to overcome growth inhibition by SCFAs in the lumen of the large intestine.

Here, we used untargeted metabolomics to identify resources generated by S. Typhimurium virulence factor activity during gastrointestinal infection and investigated their role in countering SCFA-mediated intracellular acidification.

L.C. Radlinski, A.W.L. Rogers, L. Bechtold, H.L.P. Masson, H. Nguyen, A.B. Larabi, C.R. Tiffany, T.P.D. Carvalho, R.M. Tsolis, A.J. Bäumler
, Salmonella virulence factors induce amino acid malabsorption in the ileum to promote ecosystem invasion of the large intestine Proc. Natl. Acad. Sci. U.S.A. (2024) 121(47), e2417232121, DOI: 10.1073/pnas.2417232121.

Copyright: © 2024 The authors.
Published by the National Academy of Science. Open access.
Reprinted under a Creative Commons Attribution 4.0 International license (CC BY 4.0)

I wonder if a creationist would be brave enough to attempt to explain these advantageous abilities of Salmonella, which enable it to survive and overcome our natural defences in our intestines in terms of 'devolution' from an initially designed perfection, or, if not, explain why, if the E.coli's flagellum is proof of their designer god, as devotees of Michael J. Behe insist, it isn't also proof of their designer god's work in Salmonella.

Alternatively, perhaps they could talk us through the process by which 'sin' is able to redesign a pathological bacterium to make it better at making us sick and increasing the suffering in the world, and even tailor-making some serovars so they target specific species, one of which is human.

Malevolent Designer News - How The SARS-CoV-2 Virus Steals Proteins From Our Immune System To Protect Itself

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ChatGPT4o

AI-Generated depiction of SARS-CoV-2 virus coated in stolen proteins.

ChatGPT4o

SARS-CoV-2 “steals” our proteins to protect itself from the immune system

Although COVD-19 has been mostly brought under control by medical science and the vaccination campaign, it still kills thousands of people a year, but nowhere near the volume of deaths during the initial wave when world-wide health services came close to collapse and economies were on the point of ruin.

But there is still much to learn about why it was so virulent and successful.

To an admirer of creationism’s divine malevolence it must have seemed like a triumph of design, as it filled hospitals, killed millions and wrecked economies, helped by its supporters in the evangelical Christian churches who opposed measures to mitigate the worse effect of the virus, and then opposed the vaccination campaign with lies, scare tactics and the most infantile conspiracy theories imaginable, to help ensure the virus got to as many people as possible.

Now, a team of researcher from the Medical University of Vienna together with colleagues from the Medical University of Innsbruck have discovered how the virus protects itself from the immune system creationists believe their putative intelligent designer designed to protect us from the virus’s and other pathogens it designs to make us sick, would grace the pages of another 'intelligent design' polemic by Michael J. Behe and his Deception Institute. It depends on several components of a system being present in a classic 'irreducibly complex' system that creationists wave around as 'proof' that the locally-popular creator god is real because they can't understand how it could have evolved.

Malevolent Design - How Sleeping Sickness Parasites Are 'Designed' to Evade Our Immune System

Trypanosoma brucei

Sleeping sickness

Discovery Illuminates How Sleeping Sickness Parasite Outsmarts Immune Response | Johns Hopkins | Bloomberg School of Public Health

Trypanosoma brucei is a blood-borne eukaryote parasite that should leave believers in an intelligent designer, open-mouthed in admiration for its inventive genius. Christian fundamentalist creationists of the white supremacist persuasion should also admire the racist that, through T. brucei, has managed to keep large parts of Africa technologically under-developed due to the difficult in maintaining herds of domestic animals where the vector of these parasites - the tsetse fly - is common.

As a vector, the tsetse fly is a triumph of malevolent design which I mentioned in my popular book, The Unintelligent Designer: Refuting the Intelligent Design Hoax, but it would have been all for nothing without the nasty little T. brucei to cause sleeping sickness in humans and the debilitating disease "nagana" in cattle.

What creationist admires of the divine malevolence they believe designs these things should now be marveling at is the sheer brilliance of the design by which it manages to evade the immune system, which they believe was created by the same designer god which now regards his design as a problem to be overcome oh parasites like T. brucei can continue making Africans and their cattle sick.

Malevolent Designer News - Stand By For The Next Move In The Mpox Arms Race

Colorized transmission electron micrograph of mpox virus particles (light green) found within VERO E6 cells (teal).

NIAID Integrated Research Facility
Fort Detrick, Maryland.

Mpox virus particles

Mpox Vaccine Is Safe and Generates a Robust Antibody Response in Adolescents | NIAID: National Institute of Allergy and Infectious Diseases

As Medical science announces success in the search for a vaccine against the mpox virus currently spreading misery and suffering around the globe, we can be as sure as can be that creationism’s divine malevolence is working on a variant with an inbuilt way to evade the antibodies the vaccine produces, in just the same way it did with COVID-19 - if you believe a magic designer is behind these things, the way intelligent [sic] design creationists do.

Malevolent Design - How Chlamydia Is 'Designed' to Cause Maximum Sufferring.

Chlamydia pneumoniae

AI-generated image (ChatGPT4o)

Schematic representation of how a C. pneumoniae cell infects a human cell. The bacterium injects the protein SemD (green) into the cell, which activates the cell protein N-WASP, which in turn initiates vesicle formation.

Credit: HHU/Fabienne Kocher.

Universität Düsseldorf: Original or copy: How Chlamydia manipulate the host cell

The problem of parasites for creationists is one that, despite the best efforts of apologists like Michael J Behe of the Deception Institute, just won't go away.

Sadly, Behe shot himself in the foot with his original claim to have proven 'intelligent [sic] design in living organisms with his choice of the bacterial flagellum in E. coli, where he persuaded his willing audience that these nasty little pathogens had been intelligently designed - and by unspoken assumption, designed by the locally-popular god.

Now creationists wave his 'proof' of design as evidence for their creator god because only their god is capable of creating living organisms.

But, with characteristic double-think, creationists also argue that their god is omnibenevolent, so something else must have created parasites like E. coli, and, courtesy again of Michael J. Behe, they cite 'Sin' causing 'genetic entropy' and the absurd idea of 'devolution' this supposedly causes, as the cause of parasites and pathogens (but not the bacterial flagellum, obviously!).

The problem with that notion is that they need to do their double-think trick one more time and believe that a trait with improves a pathogens ability to live and reproduce in its host makes it somehow less perfect that one without that trait. So, in the creationist's world, an improvement is a move away from perfection!

But, with a cult that appears to believe learning is a move away from the 'perfection' of pristine ignorance (from whence comes expertise in all aspects of science), that's probably not too difficult a feat of mental gymnastics for a creationist to perform.

Malevolent Design - How Bacteria Are 'Designed' With a Protective Coat

Bacterial cell wall structure

AI generated (ChatGPT40)
With apologies for the spelling!

Study unveals a novel protective mechanism in bacterial cell wall

Structure of gram-negative cell envelope

By Jeff Dahl - Own work, CC BY-SA 4.0, Link

Here's a conundrum for creationists who have fallen for the Deception Institute's biologically nonsensical excuse for parasites - that they weren't designed by the only entity capable of designing living organisms, but by a process of 'devolution' [sic] from an initial created perfection caused by 'genetic entropy'. This excuse was hastily cobbled together by Michael J Behe when he realised his 'intelligent [sic] design' notion was making creationism's putative creator look like a pestilential malevolence, especially after Behe had gone to such lengths and scuppered his academic credentials with how 'irreducibly-complex-therefore-magically-created' E. coli flagellum, then his claim that resistance to antimalarial drugs in Plasmodium falciparum must have been designed.

The problem was that having produced an excuse for parasites that was designed to appeal to religious fundamentalists, Behe inadvertently abandoned any pretense that creationism is science not religion, by incorporating Christian fundamentalism in his excuse - initial created perfection followed by 'genetic entropy' caused by 'Sin', which depends on a belief in 'The Fall' and original sin.

Although Behe insists he's not a Christian fundamentalist YEC, his books invariably appeal to, and reinforce the prejudices of, those who are, and feed their insatiable demand for validation from the science they despise and continually attack as biased/Satanic/lies/flawed, etc.

But now we have research that shows how bacteria are 'designed' with a protective cell wall which helps them resist enzymes which would otherwise destroy them. Defensive structures and processes cannot logically be described as 'devolutionary', they therefore either evolved naturally, or, if you reject evolution in favour of intelligent [sic] design, were intelligently designed to make the bacteria better at making us sick, i.e., with malevolent intent.

Malevolent Design News - Researchers Show Another Of The Devine Malevolence's Nasties - HIV's Little Brother HTLV-1

HTLV-1 virus-like particle

© Nature Structural & Molecular Biology/Obr et al.

A viral close-up. HTLV-1 virus-like particles with a close-up view of the building blocks forming the viral lattice.

© Nature Structural & Molecular Biology/Obr et al.

ISTA | A Viral Close-Up

Not content with increasing the suffering and misery in the world with its brilliantly designed Human Immunosuppressive Virus (HIV), creationism's favourite pestilential malevolence also produced a related virus, Human T-lymphotropic virus type 1 (HTLV-1).

HIV is a deadly, (normally) sexually-transmitted retrovirus which medical scientists has managed to bring under control, but not cure or eradicate or even produce a vaccine against. What they have produced are anti-retroviral drugs which prevent the virus replicating so it doesn't kill its victims and, more importantly it isn't passed on to sexual partners.

Sadly for creationists, they have been denied the excuse of 'genetic entropy' and 'devolution' to absolve their favourite sadist of responsibility for HIV because they have also jubilantly declared it to be a 'gay plague' sent by their 'loving' god to punish homosexuals for behaving how it designed them to behave.

HTLV-1 is not nearly so deadly as HIV when left untreated, but, being closely related to it, it uses the same modus operandi as HIV and in some cases causes cancer and neurodegenerative disease that can be more deadly and debilitating than HIV treated by anti-retroviral drugs.

Malevolent Designer News - Why Cholera is So Good at Killing Us

Vibrio cholerae

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Vibrio cholerae

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News - Experts discover the deadly genetics of cholera, which could be key to its prevention - University of Nottingham

Although good hygiene and safe drinking water have most brought cholera under control in developed societies, it is still a major kill, especially of children, in poor and technologically under-developed countries.

It was a cholera outbreak of 1849 in Soho, London, the John Snow famously showed was statistically linked to drinking water from a well in Broad Steet, eventually persuading the authorities to remove the pump handle from the well, so ending the epidemic, that Snow conformed the Germ Theory of disease and founded modern epidemiology.

The cause was later shown to be a leaking septic tank which was contaminating the water in the well, and more remotely to a baby which caught cholera elsewhere whose nappy (diaper) was washed into the sewer, introducing the Vibrio cholerae into the septic tank.

I was born and brought up in North Oxfordshire in a rural community where, a generation earlier, cholera had been the single most common cause of death of children. A perusal of the parish burial registers shows regular patterns of epidemics causing a sudden increase in child deaths.

Even in technologically advanced countries, natural disasters such as earthquakes and floods, and man-made conflicts such as those currently in Gaza and Ukraine can destroy the infrastructure and quickly lead to conditions in which cholera can further devastate an already weakened population.

It would be an especially despicable malevolence that designed an organism to exploit people in those situation to ensure there was even more suffering, but those subscribing to the intelligent design hoax are unwittingly attributing exactly that to their putative designer god.

Malevolent Designer News - How A Parasitic Wasp Targets Adult Fruit Flies

Syntretus perlmani grub emerging from the side of a fruit fly

Scale bar: 1mm

Newly-discovered parasitoid wasp, Syntretus perlmani. Scale bar: 1mm.

Moore, L.D., Chris Amuwa, T., Shaw, S.R. et al. (2024)

New species of wasp ‘hidden in plain sight’ discovered by MSU researchers | Mississippi State University

The world of parasites is a world that creationists need to turn a blind eye to (and not one blinded by a parasitic worm) because it contains abundant examples of how an intelligence that designed parasites can only be regarded as some sort of malevolent sadist who designs ways to make living things suffer, often horribly and in especially ghoulish ways - the sort of ways that only a sick mind could dream up.

Creationist cult leaders are also probably reticent about discussing parasites, given their parasitic lifestyle, but that’s a different matter.

Within the world of parasites, there are fewer better examples of the casual cruelty that characterises it than those of the many parasitoid wasps that lay their eggs in the living bodies of their host species, where their larvae feed on the body of the host, often only killing it at the last moment and sometimes manipulating its victim or reanimating its dead body to protect the parasites within it.

Very many of these parasitoid wasps attack the larvae of other insects and gain the protection of the eventual cocoon their host makes before dying, so the wasp's reproductive cycle is linked to that of its host species.

Malevolent Designer News - Creationism's Favourite Pestilential Malevolence Is Improving Its Delivery System

Invasive Asian tiger mosquito, Aedes albopicus

Aedes albopicus

Photo by James Gathany/CDC

Study identifies areas of Europe at risk from dengue fever | UK Centre for Ecology & Hydrology

For devotees of creationism's putative intelligent [sic] designer, news that it is using a new, improved mosquito to deliver dengue fever to more people, including those in the densely populated continent of Europe, will be greeted with admiration for its creative genius.

Those with a more rational, adult understanding of the evidence will see this news as a natural consequence of environmental change and exactly the sort of thing evolution can produce, precisely as the Theory of Evolution predicts.

The news is that climate change has enabled the Asian tiger mosquito, Aedes albopictus, to extend its range into Europe and with it the virus that causes dengue fever or which the tiger mosquito is a vector.