If you don’t know what pleiotropy means, you had better learn the word: when one mutational change confers multiple phenotypic effects. When it comes to antibiotic resistance, this is a bad thing–for us, anyway.
Which brings us to mcr-1, the transferable bacterial gene that confers resistance to colistin, the last line antibiotic we have against some multi-drug resistant infections such as CRE (carbapenem-resistant enterobacteriaceae; boldface mine):
MCR-1 has become an increasing concern because of the fear of rapid transferable resistance to last-resort antibiotics. Although MCR-1 confers resistance to the polymyxin antibiotic colistin, whether it also confers resistance to other antimicrobials is unclear. Here we report that MCR-1 confers cross-resistance to the cationic host antimicrobial lysozyme.
We cured mcr-1-positive Escherichia coli isolates CDF-1 and IHD86_4 (patient isolates from Switzerland and Cambodia, respectively) of their mcr-1-carrying plasmid by serial passage in lysogeny broth… When tested by broth microdilution in 25% lysogeny broth, both cured strains were four times more susceptible to colistin and twice as susceptible to polymyxin B…
We measured survival rates between mcr-1-positive isolates and cured strains in the presence of lysozyme in 25% lysogeny broth. Strains without mcr-1 were killed in the presence of lysozyme whereas the parental strains were able to grow (appendix). Specifically, mcr-1-negative strains were five to 20 times more susceptible to several concentrations of lysozyme when comparing survival rate….
Resistance to the host’s innate immune defences could drive plasmid maintenance in strains carrying mcr-1, mcr-2, or other transferable resistance plasmids, leading to propagation of colistin resistance.
That last sentence is the doozy. What that means is the body’s own immune system could selectively favor transferable colistin resistance. Unlike antibiotics, it’s not like we can stop using our innate immune system. Once it spreads, it might be really hard to get rid off, so we please get colistin out of the agricultural system?
When I first heard about mcr-1, I remember saying to someone, “I don’t want to be irresponsible and speculate that our own innate immune system could be affected by mcr-1.”