Investigators in China have found that the presence of the MCR-1 gene has increased in humans over a period of 5 years.
Investigators in China have found that the presence of the mobilized colistin resistance (MCR-1) gene has increased in humans over a period of 5 years.
Colistin, also known as polymyxin E, is an antibiotic that has been on the market for 50 years. It was one of the very first antibiotics shown to be effective against Gram-negative bacteria like Pseudomonas aeruginosa. As of the 1970s, use of colistin has decreased because of concerns about nephrotoxicity and neurotoxicity. Currently, it is used as a last resort therapy for infections caused by multidrug-resistant (MDR) Gram-negative bacteria, such as P. aeruginosa, Klebsiella pneumoniae, and Acinetobacter baumannii.
Colistin’s mechanism of action is to interact with the bacterial outer membrane and to displace the divalent cations in the lipopolysaccharide, leading to bacterial death. Bacterial resistance to colistin has been seen previously because of efflux pumps, capsule formation, and modifications to the cell wall. Recently, resistance to colistin has been detected through a plasmid-mediated mechanism in which MCR-1 is transferred between different strains of bacteria.
In a new study published in Eurosurveillance, principal investigator Guo-Bao Tian, a microbiologist at Sun Yat-sen University in Guangzhou, and his colleagues investigated MCR-1 in human fecal matter as well as in third-generation cephalosporin-resistant Enterobacteriaceae in China over 5 years, and the results were surprising.
The authors collected 8022 fecal samples from 3 hospitals in Guangzhou, China that serve over 15 million people. The samples were cultured and then sub-cultured on MacConkey agar with the addition of cefotaxime, a broad-spectrum cephalosporin antibiotic, to identify isolates that were cefotaxime-resistant. Identification of species was confirmed using 16S rDNA sequencing. The cultures were screened for MCR-1 using polymerase chain reaction (PCR).
The authors found that 497 out of the 8022 fecal samples were MCR-1 PCR positive which amounts to 6.2% of the fecal samples screened. In addition, 2.3% or 182 fecal samples were MCR-1 positive as well as cefotaxime resistant. In looking at strain diversity, the authors selected 89 isolates (45 collected pre-May 2015 and 44 collected after June 2015) for whole genome sequencing (WGS), using the Illumina platform. Out of these 89, 16 isolates failed quality control, leaving 73 sequences to analyze, of which 70 corresponded to Escherichia coli and 3 were K. pneumoniae. Most alarmingly, the authors found that there was an increase in the carriage of MCR-1 over the 5 years that the study was conducted.
Although the authors report significant increases in MCR-1 positive isolates in fecal matter, the study did not assess potential risk factors that are associated with the increasing prevalence of MCR-1. In addition, because the authors did not perform PCR directly on DNA extracted from feces and instead performed PCR on the strains that could be cultured, the authors may have underestimated their true MCR-1 colonization. Moreover, the authors did not screen for MCR-2, which has also been documented to allow bacteria to develop colistin resistance.
Regardless of these limitations, the authors were able to draw attention to the increase in human fecal carriage of MCR-1 gram-negative bacteria. This work sheds light on a potential global health concern as colistin is a last resort antibiotic for MDR bacteria and new therapeutics are needed to combat drug resistance.
Samar Mahmoud graduated from Drew University in 2011 with a BA in Biochemistry and Molecular Biology. After two years of working in the industry as a Quality Control Technician for a blood bank, she went back to school and graduated from Montclair State University in 2016 with an MS in Pharmaceutical Biochemistry. She is currently pursuing her PhD in Molecular and Cellular Biology at the University of Massachusetts at Amherst.