Vibrio cholerae
AI generated image (ChatGPT4o)
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.
What can you tell me about the bacterium, Vibrio cholerae and why it continues to be a threat to human health? Vibrio cholerae is a Gram-negative bacterium that causes cholera, a severe diarrheal disease. This bacterium thrives in brackish or saltwater environments and can also be found in contaminated freshwater, typically associated with poor sanitation and unsafe drinking water.Advocates of intelligent design should acknowledge the success their putative designer had and continues to have with the this nasty little organism that is equipped with the flagellum that Michael J. Behe has declared to have been intelligently designed because it is 'irreducibly complex', so the excuse that creationism's intelligent designer isn't responsible for these organisms, is closed to creationists, courtesy of Michael J Behe and his Deception Institute. If creationism's designer designed the flagellum of Vibrio cholerae, like it reputedly designed the flagellum of Escherichia coli, then it designed V. cholerae in the full and inerrant knowledge of what it would do.
Here’s why Vibrio cholerae continues to be a global health threat:Effective cholera control requires improving water sanitation, hygiene, and health education in at-risk areas, alongside consistent access to treatment and vaccines.
- Rapid Spread in Poor Sanitation Conditions
Cholera outbreaks often occur in areas with inadequate water treatment, sanitation, and hygiene infrastructure. Developing countries, especially those affected by natural disasters or conflict, are at high risk. The bacteria can spread rapidly through contaminated water sources and food.- Highly Infectious Nature
Vibrio cholerae produces a toxin called cholera toxin, which binds to the cells in the small intestine, causing them to release large amounts of water and electrolytes. This leads to severe dehydration and diarrhea, which can be fatal if untreated.- Asymptomatic Carriers
Many infected individuals exhibit mild or no symptoms, yet they can still spread the bacteria through fecal contamination. This complicates control efforts, as it’s hard to identify and isolate carriers.- Environmental Reservoirs
V. cholerae can persist in the environment in aquatic reservoirs (such as rivers, estuaries, and coastal waters), where it forms symbiotic relationships with plankton and other marine organisms. This environmental persistence makes cholera outbreaks cyclical and hard to eradicate.- Antibiotic Resistance
While cholera is usually treated with rehydration therapy, antibiotics may be used in severe cases. However, the rise of antibiotic-resistant strains of V. cholerae adds complexity to treatment, making it harder to manage severe outbreaks.- Climate Change and Globalization
Global warming increases the temperature of water bodies, creating favorable conditions for V. cholerae to thrive. Additionally, climate events such as flooding and hurricanes exacerbate the spread of cholera. Increasing global trade and travel also enable the bacterium to spread to new regions.- Inadequate Access to Vaccines
There are oral cholera vaccines available, but access to these vaccines is limited in many vulnerable areas. Moreover, vaccination campaigns need to be regularly implemented to maintain immunity in populations.- Public Health Infrastructure Gaps
Many of the countries at risk for cholera outbreaks lack the healthcare infrastructure to provide rapid diagnosis, treatment, and public health interventions.
Tell me more about the symbiotic relationships with plankton and other marine organisms.
Vibrio cholerae forms several interesting symbiotic relationships with marine organisms, particularly plankton and other small aquatic creatures, which help explain the bacterium's persistence and spread in aquatic environments. Here’s a deeper look into these relationships:
- Attachment to Zooplankton (Copepods)
V. cholerae is known to attach to the surfaces of zooplankton, especially copepods, a type of small crustacean that is abundant in marine and freshwater environments. The bacterium binds to the exoskeleton (chitin) of copepods, using it as both a nutrient source and a protective niche.
- Chitin Utilization: The exoskeleton of copepods is made of chitin, a polysaccharide. V. cholerae has specialized enzymes that can break down chitin into smaller molecules, which it can use for nourishment. This relationship is key for the bacterium’s survival in nutrient-poor waters.
- Population Blooms: Copepod populations often experience seasonal blooms, which coincides with cholera outbreaks. When copepods die, they release V. cholerae back into the water, increasing the risk of human exposure.
- Biofilm Formation on Plankton
In addition to copepods, V. cholerae can form biofilms on other types of plankton, such as phytoplankton (microscopic algae). Biofilms are dense communities of bacteria that adhere to surfaces and protect the bacteria from environmental stresses such as UV light, salinity changes, and predation by other microorganisms.
- Survival in Harsh Conditions: The biofilm matrix protects V. cholerae from desiccation and other environmental factors, enhancing its ability to survive during periods of poor environmental conditions.
- Infectious Reservoir: These biofilms can act as reservoirs for V. cholerae, allowing the bacteria to persist in aquatic environments for long periods, even when conditions are not conducive to free-living bacteria.
- Association with Shellfish
Shellfish, such as oysters, mussels, and crabs, filter large amounts of water as they feed, trapping V. cholerae along with other microorganisms in their digestive systems. These shellfish can harbor V. cholerae without becoming ill, but they pose a risk to humans when consumed raw or undercooked, as the bacteria can then infect the human host.
- Transmission Route: Shellfish consumption is a common route of cholera infection in coastal regions where contaminated waters harbor these organisms.
- Symbiosis with Algal Blooms
V. cholerae also has associations with algal blooms, particularly those of phytoplankton. During a bloom, the increased availability of organic matter provides a nutrient-rich environment for the bacterium, leading to higher concentrations of V. cholerae in the water.
- Environmental Cycling: V. cholerae can exploit the growth and decay of algae, thriving in the nutrient-rich waters that follow the death of phytoplankton after a bloom. Seasonal and environmental changes that drive plankton blooms, like warmer temperatures or excess nutrients, can increase the presence of V. cholerae.
- Aquatic Reservoirs as Natural Habitats
The natural aquatic reservoirs, such as estuaries, coastal waters, and river mouths, create ecosystems where Vibrio cholerae is a normal part of the microbial community. The bacterium can live in symbiosis with both phytoplankton and zooplankton in these ecosystems, forming a cycle where it moves between different hosts and environmental niches.
- Quiescent State: In harsh conditions, V. cholerae can enter a viable but non-culturable (VBNC) state, in which it is alive but not actively growing. This state allows it to survive until favorable conditions return, such as during a plankton bloom.
Implications for Cholera Outbreaks
These symbiotic relationships are significant because they explain how Vibrio cholerae persists in the environment between outbreaks, and how it can re-emerge in human populations when conditions are right. Outbreaks often follow environmental changes that favor plankton growth, such as increased water temperature (due to climate change), seasonal changes, or nutrient runoff from agriculture.
- The copepod association also highlights the role of water filtration systems in cholera control. Proper water treatment methods that remove plankton can greatly reduce the bacterial load and lower the risk of cholera transmission.
Understanding the bacterium’s ecological relationships is crucial for predicting and managing cholera outbreaks, particularly in coastal regions.
Currently, V. cholerae causes up to 4 million cases and as many as 143,000 deaths each year. In Bangladesh alone, where cholera is a persistent danger, 66 million people are at risk, with over 100,000 cases and 4,500 deaths annually.
Now scientists working at Nottingham University have identified what exactly it is about V. cholerae that makes it so deadly, in addition to its ability to evolve and evade antibiotics and become ever more virulent in the face of medical science's efforts to control it.
The team, led by Professor Tania Dottorini from the University of Nottingham, in collaboration with Bangladesh’s Institute of Epidemiology, Disease Control and Research (IEDCR), International Centre for Diarrhoeal Disease Research, Bangladesh, and North South University, have just published their findings in the journal Nature communications
They have found that V. cholerae can evolve rapidly and has recently acquired a greater ability to resist attack by phage viruses, commonly found in the human gut microbiota. It has also evolved improved its ability to tolerate the acid conditions in the gut, to spread more easily and to be more virulent than earlier strains.
Experts discover the deadly genetics of cholera, which could be key to its prevention
Experts have used a cutting-edge computational approach to discover the genetic factors that make the bacteria behind cholera so dangerous - which could be key to preventing this deadly disease.
The breakthrough study, published in Nature Communications, is led by Professor Tania Dottorini from the University of Nottingham, in collaboration with Bangladesh’s Institute of Epidemiology, Disease Control and Research (IEDCR), International Centre for Diarrhoeal Disease Research, Bangladesh, and North South University.
The innovative research combines machine learning, genomics, genome-scale metabolic modelling (GSMM), and 3D structural analysis to uncover the genetic secrets of Vibrio cholerae – the bacteria behind cholera.
Cholera is a deadly diarrheal disease, that continues to threaten millions worldwide, with up to 4 million cases and as many as 143,000 deaths each year. In Bangladesh alone, where cholera is a persistent danger, 66 million people are at risk, with over 100,000 cases and 4,500 deaths annually.
Vibrio cholerae, is evolving in ways that make the disease more severe and harder to control, but until now, scientists have struggled to pinpoint the exact genetic factors driving these changes. There is even less knowledge about the genomic traits responsible for the severity of cholera resulting from these lineages. About 1 in 5 people with cholera will experience a severe condition owing to a combination of symptoms (primarily diarrhoea, vomiting, and dehydration).
In this new study, the UK-Bangladeshi research team analysed bacterial samples from cholera patients across six regions in Bangladesh, collected between 2015 and 2021. They identified a set of unique genes and mutations in the most recent and dominant strain of Vibrio cholerae responsible for the devastating 2022 outbreak. These genetic traits are linked to the bacteria’s ability to cause severe symptoms like prolonged diarrhoea, intense abdominal pain, vomiting, and dehydration—symptoms that can lead to death in severe cases.
Professor Tania Dottorini
By identifying the key genetic factors that drive both the transmission and severity of cholera, we've taken a significant step toward developing more effective treatments and targeted interventions. This could save thousands of lives, not just in Bangladesh, but globally.
Professor Tania Dottorini, lead author
School of Veterinary Medicine and Science
University of Nottingham
Sutton Bonington, Loughborough, Leicestershire, UK.
The findings of the study also revealed that some of these disease-causing traits overlap with those that help the bacteria spread more easily. The findings show how these genetic factors enable Vibrio cholerae to survive in the human gut, making it more resilient to environmental stress and more efficient at causing disease. This research highlights the complex interactions between the bacteria's genetic makeup and its ability to cause severe illness.
This new computational framework is a major step forward in the fight against cholera. By identifying the key genetic factors that make Vibrio cholerae more dangerous, scientists can develop better treatments and more targeted strategies to control and prevent future outbreaks. This breakthrough offers new hope for improving public health in Bangladesh and potentially saving countless lives worldwide.
Our findings open the door to a new era of cholera research, where we can develop tools to predict and potentially prevent severe outbreaks before they occur. The ultimate goal is to translate these insights into real-world solutions that protect vulnerable populations.
This breakthrough was only possible through the close collaboration between our UK and Bangladeshi partners. Together, we've combined cutting-edge computational tools with local expertise to tackle one of the most pressing public health challenges.
Professor Tania Dottorini.
The research is funded by Research England, the Global Challenges Research Fund, and the Medical Research Council (MRC).
The full study can be found here.
More information is available from Professor Tania Dottorini from the School of Veterinary Medicine and Science at tania.dottorini@Nottingham.ac.uk.
Abstract
In Bangladesh, Vibrio cholerae lineages are undergoing genomic evolution, with increased virulence and spreading ability. However, our understanding of the genomic determinants influencing lineage transmission and disease severity remains incomplete. Here, we developed a computational framework using machine-learning, genome scale metabolic modelling (GSSM) and 3D structural analysis, to identify V. cholerae genomic traits linked to lineage transmission and disease severity. We analysed in-patients isolates from six Bangladeshi regions (2015-2021), and uncovered accessory genes and core SNPs unique to the most recent dominant lineage, with virulence, motility and bacteriophage resistance functions. We also found a strong correlation between V. cholerae genomic traits and disease severity, with some traits overlapping those driving lineage transmission. GSMM and 3D structure analysis unveiled a complex interplay between transcription regulation, protein interaction and stability, and metabolic networks, associated to lifestyle adaptation, intestinal colonization, acid tolerance and symptom severity. Our findings support advancing therapeutics and targeted interventions to mitigate cholera spread.
Introduction
Cholera is an acute diarrhoeal disease. Worldwide, 1.3 billion people are estimated to be at risk and approximately 1.3 to 4 million cases occur annually, with 21,000 to 143,000 resulting in death1,2. In Bangladesh alone, where cholera is endemic, an estimated 66 million people are at risk of cholera with at least 100,000 cases and 4500 deaths per year1,3. Globally the O1 serogroup remains the primary cause of cholera1,2. The O1 serogroup is divided into the main serotypes Ogawa and Inaba, and subdivided into two biotypes, classical and El Tor (7th pandemic), which are genotypically and phenotypically distinct4,5,6. V. cholerae has shown an extraordinary capacity to undergo genetic and phenotypic changes over time, giving rise to successive waves of genetically and phenotypically diverse pandemic clones. These variants exhibit increased virulence, pathogenicity, resistance and spreading capability7,8.
Recently, distinctive lineages belonging to the 7th pandemic El Tor (7PET) wave-3 have been observed circulating in Bangladesh9,10,11. The two most prominent circulating lineages identified over the last 20 years are BD-1 and BD-29,10,11, and more recently BD-1.2, responsible for the latest 2022 massive outbreak in the country10. Genomic analysis revealed variations between BD-1.2 and BD-2 in the Vibrio seventh pandemic island II (VSP-II), Vibrio pathogenic island 1 (VPI-1), mobile genetic elements, phage-inducible chromosomal island-like element (PLE), and SXT-related integrating conjugative elements (SXT ICE)10. Despite the advances of genomic analysis, the complete genomic repertoire and the mechanisms causing the greater transmission of BD-1.2 remain unknown. Gaps persist in our knowledge regarding whether coding or non-coding single nucleotide polymorphisms (SNPs), or accessory genes, drive the evolutionary shifts. It remains unclear whether gene regulation, metabolic or molecular networks, or folding events play a role. There is even less knowledge about the genomic determinants responsible for the severity of cholera resulting from these lineages. About 1 in 5 people with cholera will experience a severe condition owing to a combination of symptoms (primarily diarrhoea, vomiting and dehydration)12. Amongst the major symptoms, watery diarrhoea characteristic of cholera is caused by the cholera toxin (CT)4,5,6. The V. cholerae El Tor responsible for the current cholera pandemic has become more virulent by undergoing several changes in CTX genotype and acquiring virulence-related gene islands13,14.
In this study, we developed a reference-agnostic machine learning method, coupled with genome-scale metabolic modelling (GSMM) and protein structural analysis, to achieve two key objectives as outlined below. The first objective was to identify the genetic variations and signatures of the BD-1.2 lineage evolution beyond what has been found so far10. Our analysis considered 129 V. cholerae isolates from diarrhoea samples collected between 2015 and 2021, from patients admitted to the icddr,b hospital in Bangladesh. Several genomic studies investigated the evolution of lineages from 1991 to 2017, as well as in 20229,10,11. However, there remains a gap in research during the intervening period. In our analysis, we discovered a set of 77 SNPs within the coding genome (mapped to 50 known genes), along with 12 annotated accessory genes, including some associated with antibiotic resistance, virulence, motility, colonisation, biofilm formation, acid tolerance and bacteriophage resistance, identified as correlated with BD-1.2 transmission. Our findings go beyond what was recently discovered9,10,11 for the lineage.
The second objective was to investigate if correlations exist between the genomic determinants of BD-1.2 strains and clinical manifestations among hospitalised patients from whom the isolates were collected. Machine learning revealed the existence of correlations between genetic determinants in V. cholerae and clinical symptoms (duration of diarrhoea, number of stools, abdominal pain, vomiting and dehydration). Overall, the analysis revealed an overlap of 11 mutations, four accessory genes, and one intergenic SNP between the unique genomic determinants associated with BD-1.2 transmission and the clinical symptoms linked to this lineage. Additionally, a distinct set of 17 mutations, 39 accessory genes, and four intergenic SNPs were found exclusively linked to the severity of clinical symptoms. Through detailed GSMMs and 3D structure analysis of these genes, we inferred the mechanistic basis behind the selection of these genomic drivers in BD-1.2 and link to severity of the symptoms.
Fig. 3: An overview of the metabolic pathways associated to the core genes underlying the BD-1.2 and BD-2 lineages separation.
All genes annotated were found to have reduced flux span through the metabolic system when knocked out. Genes coloured in blue have a significant different allelic distribution between BD-1.2 and BD-2, associated metabolic pathways are labelled in purple. All 3D protein structures were generated in Alphafold123 under a Creative Commons Attribution 4.0 license (CC-BY 4.0), no changes were made.Fig. 6: An overview of the metabolic pathways impacted by statistically significant genes underlying clinical symptoms.
All genes annotated were found to have reduced the flux span through the metabolic system when knocked out. Genes coloured in pink and purple carried mutations or are accessory genes associated to the clinical symptom, respectively, and connected metabolic pathways (labelled in blue). The genes coloured in purple were also found as statistically significant in differentiating the BD-2 and BD-1.2 lineages (see previous sections). All 3D protein structures were generated in Alphafold123 under a Creative Commons Attribution 4.0 license (CC-BY 4.0), no changes were made.
Maciel-Guerra, A., Babaarslan, K., Baker, M. et al.
Core and accessory genomic traits of Vibrio cholerae O1 drive lineage transmission and disease severity.
Nat Commun 15, 8231 (2024). https://doi.org/10.1038/s41467-024-52238-0
Copyright: © 2024 The authors.
Published by Springer Nature Ltd. Open access.
Reprinted under a Creative Commons Attribution 4.0 International license (CC BY 4.0)
Now, which creationist is going to stick his/her neck out and declare that the complexity in those metabolic pathways was not the work of their favourite putative designer god, or that the resulting improved ability to infect and kill people was not the work of the same designer?
Of course, evolution by natural selection acting on variance in a population of billions, or even trillions of bacteria, replicating in a matter of minutes rather than days, weeks or months, in a selective environment in which those best able to infect new victims and survive are going to leave more descendants than those less able, is perfectly capable of producing these genetic changes because even the billion to one chance will occur several times a day, and any advantage it gives the carrier means it will tend to increase exponentially in the gene pool of the bacterial population.
But for inexplicable reasons, creationists would prefer people to think that sort of evolutionary change is impossible, so it must have been due to design by their putative designer god - the pestilential malevolence.
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