Colistin-Resistant MCR-1 Genes Found in Bacteria on Hospital Surfaces

As drug resistance continues to grow as a serious global health threat, there is a growing need to learn more about what sparks the spread among bacteria. A particularly threatening form of resistance is plasmid-mediated colistin resistance driven by the mcr-1 gene. The antibiotic colistin is often used as a last-resort against multidrug-resistant (MDR) gram-negative bacteria.

This makes the findings of a new study from Italy all the more concerning as the team of investigators from the University of Ferrara discovered that that 8.3% of Enterobacteriaceae collected from hospital surfaces harbored the mcr-1 gene. This finding proves that the plasmid has the ability to spread in key human pathogens.

The mcr-1 gene was first detected in China in 2016, with implications that resistance spread from animals to humans through horizontal gene transfer. The gene was found in various gram-negative bacteria including Klebsiella pneumoniae, Enterobacter, Salmonella and Citrobacter.

The emergence of the gene in different bacteria is a cause for concern because it limits the treatment options for infections sustained by carbapenem-resistant Enterobacteriaceae (CRE).

In the study out of Italy, the investigators sought to determine the diffusion of mcr-1 driven colistin resistance in the hospital environment. The team searched for the presence of the gene in a library of 300 Enterobacteriaceae samples collected from the surfaces of 8 hospitals in Italy between 2016 and 2017. (Surface contamination is known to contribute to the onset of hospital-acquired infections which are often sustained by multidrug-resistance.)

Surface samples were collected from 3 points in hospital rooms and then grown in MacConkey broth for 48 hours to amplify the Enterobacteriaceae population. Aliquot of grown bacterial was frozen for subsequent identification and functional studies. The remainder was used for DNA extraction and analyzed for the mcr-1 gene by nested polymerase chain reaction (PCR). Plasmid pBAD24::mcr-1 was used as a positive control and a universal panbacterial PCR was used as a control of DNA amplification.

The results reveal that 25 (8.3%) of the Enterobacteriaceae samples harbored the mcr-1 gene. The positive samples were culturally isolated on MacConkey agar plates and identified at the species level by biochemical typization and Vitek-2 systems and tested for drug susceptibility by disc diffusion and brother microdilution.

Different species were found to be harboring the mcr-1 gene including K pneumoniae, K oxytoca, E coli, Acinetobacter lwoffi, E cloacae, E agglomerans, C freundii, Pseudomonas aeruginosa, and P putida, suggesting that the gene is spreading to many gram-negative bacteria responsible for infections in the clinical settings.

All mcr-1-carrying isolates were colistin-resistant and the results from the disc-diffusion method revealed all colistin-resistant isolates were resistant to at least 2 or more antimicrobial drugs effective against Enterobacteriaceae, exhibiting an MDR phenotype.

The data imply that mcr-1 carrying Enterobacteriaceae can be detected on hospital surfaces with higher frequency than in clinical isolates, indicating that this gene has the ability to spread in key human pathogens. Furthermore, surface contamination over time might lead to the spread of colistin resistance among gram-negative bacteria.

Although the findings may represent a potential reservoir of threatening nosocomial pathogens and favor their diffusion in hospitalized patients, there is currently no specific monitoring to control it. The investigators suggest surveillance for mcr-1-driven colistin resistance might include not only clinical samples but also environmental analyses and clinically relevant gram-negative species to control and counteract the increase of untreatable infections.