Laboratory studies and whole genome sequencing of Vibrio cholerae, the organism which causes cholera, done by a team of researchers at RGCB has identified a mutation in one of the strains which makes it resistant to doxycycline, one of the mainstay antibiotics and the drug of choice to treat cholera.
The V57L mutation in the RpsJ protein of the organism was identified to be important in rendering it resistant to doxycycline.
Importantly, researchers found that this mutation in the V. cholerae strain can be triggered spontaneously in the environment too because of long-term exposure to antibiotic residues, indicating that stricter controls need to be brought in to prevent the indiscriminate use of antibiotics.
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The study, ‘Adaptive laboratory evolution of Vibrio cholerae to doxycycline associated with spontaneous mutation,’ by Lakshmi Narendrakumar
Pathogens usually acquire resistance to antimicrobial compounds by accumulation of spontaneous mutation or horizontal gene transfer.
“Although the emergence of antimicrobial resistance by accumulation of spontaneous mutation is less common in V. cholerae, we hypothesise that long-term exposure to antibiotic residues in the environment can alter the microbial community structure and function and cause spontaneous mutations which make V. cholerae more resistant,” Sabu Thomas, Scientist, RGCB and principal investigator of the study, said.
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In the present study, researchers used a technique, adaptive laboratory evolution (ALE) as well as whole-genome sequencing and molecular docking studies to identify putative mutations related to doxycycline resistance in V. cholerae isolates.
Although cholera is self-limiting and rehydration therapy serves as the primary treatment for the disease, antibiotics are also being used as an adjunct treatment.
Doxycycline is used to treat cholera patients in India. Apart from being used to treat bacterial and parasitic infections in humans, doxycycline is also widely used in veterinary medicine and the presence of doxycycline residues in the environment is well-documented .
“The ALE experiment, wherein V.cholerae strain was exposed continuously to a specific concentration of doxycycline over a period, proved that sustained exposure to the antibiotic can lead to the strain developing resistance to it and that a similar scenario is possible in the environment,” Dr. Thomas said.
Researchers also illustrated for the first time that the doxycycline stress induced co-resistance to different classes of antibiotics, including colistin, a last-resort antibiotic to treat extensively drug-resistant bacteria, which should sound the warning bells on the indiscriminate use of antibiotics.
Interestingly, the same doxycycline resistant strain showed collateral sensitivity to azithromycin and kanamycin antibiotics.
In this study, 97% of the V. cholerae isolates were found to be multidrug-resistant
While the reduced susceptibility of V. cholerae strains to doxycycline over the years has been observed in earlier studies too, the ALE experiment revealed that the reduced susceptibility was a result of the RpsJ V57L mutation
“This study emphasises that antibiotic residues in environments could drive the evolution of clinically relevant pathogens to acquire high level resistance. Strict regulations on the indiscriminate use of antibiotics is the need of the hour and antimicrobial resistance should be fought on the ‘One Health’ platform, as has been envisaged in the State’s AMR action plan,” Dr. Thomas said.