Tuesday, 14 May 2019

Malevolent Designer News - Winning The Antibiotic Arms Race

The mcr-9 gene's protein structure graphic depicts the differing protein chains (solid color ribbons) and the protein surface (mesh) surrounding it.
Credit: Ahmed Gaballa/Cornell University
Cornell scientists discover new antibiotic resistance gene | Cornell Chronicle

Creationism's malevolent designer has been at it again in its arms race with human medical science, and it seems to have gone into overdrive.

As Cornell University food scientists have discovered, it has created a new 'diabolical' gene to convey resistance in bacteria to our antibiotic of last resort, colistin.

And not content with giving that resistance to a bacterium like salmonella, it has made the gene fully transferable to other species via a plasmid, so, by horizontal gene transfer, any bacteria can now acquire resistance to colistin. Colistin has been designated by the World Health Organisation as a highest-priority antibiotic. Unless we can find a better one or find some new way of killing bacteria when they infect us, that's it. We will have run out of options.

Talk about belt and braces in its plan to defeat medical science and make humans sick and die like in the good old days before we discovered antibiotics! In that golden age, humans, especially children, could and would frequently die from an infected scratch, thorn prick, strep throat, or tooth abscess. Then we discovered penicillin and the malevolent designer immediately went into arms-race mode and started frantically redesigning one bacteria after another as we discovered more antibiotics and as resistance to existing ones appeared.

Mcr-9 is the latest of the malevolent designer's colistin resistance genes, the first only being discovered four years ago. It seems to have gone in to overdrive.

The new 'diabolical' gene is known as mcr-9, the ninth in a line of related genes, each one a mutation of one of the others. It was found when the food scientists were examining the genome of the foodborne pathogen, salmonella. Its DNA similarity to other genes that give resistance to colistin suggested that mcr-9 could do the same. However, the strain of salmonella being examined was not a resistant strain, but when the mcr-9 gene was inserted into a non-pathogenic, non-resistant strain of Escherichia coli (E. coli) it acquired colistin resistance, proving that mcr-9 is indeed a new colistin resistance gene.

The results of the research were published open access a few days ago in mBio, an online journal of the American Society for Microbiology.

Mobilized colistin resistance (mcr) genes are plasmid-borne genes that confer resistance to colistin, an antibiotic used to treat severe bacterial infections. To date, eight known mcr homologues have been described (mcr-1 to -8). Here, we describe mcr-9, a novel mcr homologue detected during routine in silico screening of sequenced Salmonella genomes for antimicrobial resistance genes. The amino acid sequence of mcr-9, detected in a multidrug-resistant (MDR) Salmonella enterica serotype Typhimurium (S. Typhimurium) strain isolated from a human patient in Washington State in 2010, most closely resembled mcr-3, aligning with 64.5% amino acid identity and 99.5% coverage using Translated Nucleotide BLAST (tblastn). The S. Typhimurium strain was tested for phenotypic resistance to colistin and was found to be sensitive at the 2-mg/liter European Committee on Antimicrobial Susceptibility Testing breakpoint under the tested conditions. mcr-9 was cloned in colistin-susceptible Escherichia coli NEB5α under an IPTG (isopropyl-β-d-thiogalactopyranoside)-induced promoter to determine whether it was capable of conferring resistance to colistin when expressed in a heterologous host. Expression of mcr-9 conferred resistance to colistin in E. coli NEB5α at 1, 2, and 2.5 mg/liter colistin, albeit at a lower level than mcr-3. Pairwise comparisons of the predicted protein structures associated with all nine mcr homologues (Mcr-1 to -9) revealed that Mcr-9, Mcr-3, Mcr-4, and Mcr-7 share a high degree of similarity at the structural level. Our results indicate that mcr-9 is capable of conferring phenotypic resistance to colistin in Enterobacteriaceae and should be immediately considered when monitoring plasmid-mediated colistin resistance.

Colistin is a last-resort antibiotic that is used to treat severe infections caused by MDR and extensively drug-resistant (XDR) bacteria. The World Health Organization (WHO) has designated colistin as a “highest priority critically important antimicrobial for human medicine” (WHO, Critically Important Antimicrobials for Human Medicine, 5th revision, 2017, https://www.who.int/foodsafety/publications/antimicrobials-fifth/en/), as it is often one of the only therapies available for treating serious bacterial infections in critically ill patients. Plasmid-borne mcr genes that confer resistance to colistin pose a threat to public health at an international scale, as they can be transmitted via horizontal gene transfer and have the potential to spread globally. Therefore, the establishment of a complete reference of mcr genes that can be used to screen for plasmid-mediated colistin resistance is essential for developing effective control strategies.

Carroll, L. M., Gaballa, A., Guldimann, C., Sullivan, G., Henderson, L. O., & Wiedmann, M. (2019).
Identification of Novel Mobilized Colistin Resistance Gene mcr-9 in a Multidrug-Resistant, Colistin-Susceptible Salmonella enterica Serotype Typhimurium Isolate.
, 10(3). doi: 10.1128/mBio.00853-19

Copyright: © The Authors
Published Open Access
Reprinted under the terms of a Creative Commons Attribution 4.0 International license. (CC-BY 4.0)

The one good piece of news is that now we know mcr-9 exists hospitals can test for it and isolate patients who have been infected with resistant strains, so at least trying to protect other patients. Knowing the structure of the gene and of the protein it produces also gives us a chance to develop more tools to combat it - so giving the arms race cycle another turn and giving the malevolent designer another problem to solve.

Or at least, this is what creationist ID advocates would have us believe, even if they can't face this fact themselves. If there were really an intelligent designer, examples such as this would make it impossible not to believe this designer is malevolent and is actively, and very inventively, determined to make us sick and take us back to the days before antibiotics.

The problem ID advocates have is that they need to pretend ID is not creationism dressed in a lab coat but is a real, scientific alternative to the science of evolution. Yet, when challenged to explain these examples of malevolent intent (if we assume intelligent design for a moment) they invariably fall back (pun intended) on 'The Fall' when 'sin entered the world'.

To avoid explaining it as evolution, ID advocates need to incorporate not science, but superstition and Bible literalism into their 'explanation', so exposing ID as religion in disguise.

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1 comment :

  1. Indeed, it is difficult to square the inherent 'evil' in the world with an all loving deity. ID adherents seem happy to accept the concept of 'sins of the fathers' without commenting on how unfair this really is. I'm sure they would be unhappy to be hanged because a previous ancestor stole a sheep. God's view on justice is unjust and blatantly absurd and immoral. As for antibiotics: it seems we are losing this evolutionary race and we need to consider alternative strategies to combat bacterial resistance. https://flaxensaxon.blogspot.com/2019/04/antibiotic-resistance-of-doom.html


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