Mechanism of colistin resistance in food Klebsiella bacteria unravelled
A study carried out in Chennai has found bacteria resistant to colistin drug, a last-line antibiotic, in 51 of the 110 (46%) fresh food samples (poultry, mutton, fish, and vegetables) tested. Though colistin-resistant bacteria have been found in food samples in more than 30 countries, this is the first time researchers in India have looked for and found them in fresh food.
More importantly, the researchers, led by Dr. Abdul Ghafur of Apollo Cancer Institute, Chennai, have for the first time uncovered the mechanism by which Klebsiella pneumoniae bacteria in food samples develop resistance to colistin.
While mcr-1 gene in E. coli confers resistance to colistin drug, mutations and insertional inactivation in mgrB gene are responsible for colistin resistance in Klebsiella. In the case of insertional inactivation, an external genetic element (called insertion sequence) gets inserted into a normal mgrB gene leading to its inactivation. Once the mgrB gene gets inactivated, the Klebsiella bacteria become resistant to colistin antibiotic.
“In clinical settings, the mcr-1 gene is less significant than the mgrB gene mutations for colistin resistance. This is because most of colistin resistance seen in clinical settings comes from Klebsiella bacteria and not E. coli,” says Dr. Ghafur. “The mechanisms for colistin resistance in human Klebsiella are well established. But nobody had earlier identified mgrB mutation and insertions in food Klebsiella providing evidence for food link.” The results of the study were published in the Journal of Global Antimicrobial Resistance.
The mcr-1 gene is found in the plasmid (a small DNA molecule outside the chromosome) of the bacteria and so can easily get transmitted to other bacteria thus spreading resistance. However, the mgrB gene is located in the chromosome of the bacteria and so less likely to spread. The researchers have now unravelled how colistin resistance spreads in Klebsiella bacteria despite mgrB gene being confined to the chromosome.
How resistance spreads
Once the insertion sequence inactivates the mgrB gene and makes the bacteria colistin resistant, the insertion sequence moves out from the chromosome to the plasmid of the bacteria. Once inside the plasmid, the insertion sequence can easily spread to other bacteria. Once it spreads to another bacterium, the insertion sequence moves from the plasmid to the chromosome where it gets inserted into the mgrB gene making it inactive. “This is how colistin resistance spreads in Klebsiella bacteria even though the mgrB gene is found inside the chromosome,” says Dr. Ghafur, technical advisory member of India’s national antibiotic policy.
The researchers first identified colistin-resistant Klebsiella in the food samples. Then they looked and found mgrB gene mutation in Klebsiella. “We identified 30 samples with colistin-resistant Klebsiella. Of the 30 samples, six had insertion sequences. This is the first time that mgrB gene mutation and the presence of insertion sequence have been identified in food Klebsiella,” he says. “This finding has remarkable public health significance as colistin resistance in food Klebsiella can spread to humans.”