“When antibiotics first came out, nobody could have imagined we’d have the resistance problem we face today. We didn’t give bacteria credit for being able to change and adapt so fast.” -Bonnie Bassler
Antibiotic resistant superbugs have dominated health-related news recently, warning of an impending post-antibiotic apocalypse where current antibiotics are no longer effective. Though it is true that antimicrobial resistance is increasing quickly and the effectiveness of many antibiotics is dwindling, much of what has been reported recently about a colistin resistant bacteria isolated in the U.S. may not be completely true.
Prior cases of colistin resistant bacteria in the United States
A recent paper from the Walter Reed Multidrug-resistant Organism Repository and Surveillance Network (MRSN) documenting the first occurrence of MCR-1 mediated colistin resistant infection has spurred great attention from the popular media. Despite what the news media seem to suggest, this case is not the first occurrence of colistin resistant bacteria in the United States. For example, in 2011 the U.S. National Institutes of Health Clinical Center reported an outbreak of carbapenem-resistant Enterobacteriaceae infections where 11 of the 18 patients died. Some of these isolates were resistant to colistin due to spontaneous mutations in chromosomally-encoded membrane proteins (likely transporters). In fact, one isolate acquired colistin resistance during treatment. Mutations in these membrane proteins may reduce drug influx and thus increase resistance to colistin.
Plasmid-mediated colistin resistance
One significant difference from past cases of colistin resistance in the U.S. is that the case documented by MRSN is first case of MCR-I mediated colistin resistance isolated from a patient in the U.S.. The mcr-1 gene was first identified during routine testing of livestock in China, marking the first known incidence of plasmid-mediated colistin resistance in Enterobacteriaceae (published November 2015). Plasmids are small circular pieces of DNA capable of self-replicating and transferring to other bacteria. Many times, plasmids encode genes for antimicrobial resistance elements. Interestingly, the patient from the MRSN report did not travel in the five months prior to the infection. So how did this individual acquire an MCR-1 mediated colistin resistant infection? The scientists do not know for sure, but clinical isolates submitted to their clinical microbiology laboratory are now being tested for resistance to colistin. Since the identification of MCR-1 in November 2015, many other countries have identified the mcr-1 gene from sources such as food, livestock, and humans.
One important point to note is that antibiotic resistance elements encoded on plasmids have a dramatically broader impact than those encoded on the chromosome. Since plasmids are easily transferred from one bacterium to another through transformation, conjugation or transduction mechanisms, antimicrobial resistance genes are capable spreading rapidly to other bacteria. Thus, a pathogen previously sensitive to an array of antibiotics is capable of acquiring resistance to multiple antibiotics by obtaining plasmids carrying resistance elements. In this case, what is worrisome is that the mcr-1 gene may be passed on to bacteria resistant to another drug of last resort (ex: carbapenem resistant Enterobacteriaceae).
Antimicrobial resistance has become a global problem due to the frequent use of antibiotics in raising livestocks in addition to overprescribing antibiotics in the medical setting. Fighting antimicrobial resistance will need to involve not only research effort from scientists but efforts from policy makers as well as raising awareness for the prudent use of antibiotics.
