Mechanism of colistin resistance in food Klebsiella bacteria unravelled

Klebsiella pneumoniae - NIAID

Klebsiella pneumoniae: Photo: NIAID

Researchers found colistin-resistant bacteria in 49% vegetable, meat samples in Chennai. They have for the first time deciphered the mechanism by which food Klebsiella bacteria develop resistance to colisitin, a last-line antibiotic. Mutations and insertional inactivation of the mgrB gene, which is present in the chromosome, are responsible for colistin resistance in Klebsiella.

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.”

Indiscriminate use in animals

Colistin is extensively used in veterinary practices as a growth promoter. The powerful antibiotic kills the bacteria in the animal gut leading to greater absorption of the animal feed thus making the animals grow fat and fast. Up to 70% of antibiotics manufactured in the world are used as a growth promoter in animals.

The extensive usage of colistin in animals leads to generation of colistin-resistant bacteria in poultry and freshwater fish. The use of chicken litter as a manure in agriculture results in transmission of the colistin-resistant bacteria to vegetables.

There is a greater risk of transmission of colistin-resistant bacteria form fresh vegetables and meat to humans. Though cooking kills the bacteria, the possibility of cross-contamination of the bacteria prior to cooking serves as mode of entry into humans.

“Many countries including China have already banned the use of colistin as a growth promoter. Indian health and agricultural ministries are now planning a similar ban,” he says.

Published in The Hindu on September 29, 2018