Decoding Superbugs: Cracking the code of antibiotic resistance
In 2014, the WHO’s Assistant Director-General for Health Security, Dr Keiji Fukuda, declared that “Without urgent, coordinated action by many stakeholders, the world is headed for a post-antibiotic era, in which common infections and minor injuries which have been treatable for decades can once again kill.” 12 years later, it is still difficult for a layperson to wrap their head around that statement. Could we really die from a mere papercut Healthcare workers who are on the frontline know the havoc these resistant pathogens have wreaked on patients. Antimicrobial Resistance (AMR) is a silent pandemic which seems to be reaching a boiling point, ready to break into the mainstream. It is a situation which Dr. Saugata Hazra of IIT-Roorkee is working tirelessly to prevent.
In our extensive discussion with him, Dr Hazra explained AMR through the lock-and-key analogy. Antimicrobials are a specific key which helps us unlock a certain lock within the bacterium, allowing us to kill it. Unfortunately, the story doesn’t end there. Through the process of evolution, several adaptations have been seen in bacteria which help them survive antimicrobial treatment. Building upon the analogy, bacteria have been seen to change the lock (mutation in the AMR target), destroy the key (as is the case with beta- lactamase enzymes), hold the door shut (modification of the porin proteins), among others,such as bypassing the AMR-affected pathway. Dr Hazra correctly points out that what makes this situation challenging is that we aren’t trying to best a single bacterium. We’re taking on evolution itself.
Dr Hazra’s group looks into AMR produced by beta-lactamase enzymes. These enzymes are highly efficient at degrading beta-lactam-based antibiotics such as the famous penicillin. They can also deactivate carbapenems, which are considered to be the last-line therapeutics against resistant bugs. Beta-lactamase enzymes have been observed to be highly adaptable. Even mutations far from the active site are known to produce escape variants. These features make them an ideal candidate for study. Here’s where Dr. Hazra’s structural biology approach becomes crucial. It reveals exactly what has changed in a target's structure, allowing it to resist antibiotics. Unveiling the structure of proteins involved in conferring resistance also exposes new targets for the development of therapeutics.
He also collects microbial samples from over 90 hospitals, as well as from localrivers for metagenomic analysis. This analysis provides a clear picture of the emerging resistance scenario. He uses a DTMS approach - Diagnosis, Therapeutics, Mapping, and Surveillance to tackle the AMR crisis. Diagnosis is a crucial step. If a physician cannot instantly know what antibiotics a microbe is resistant to, they will have to use a crude, trial-and-error method to find out. To ensure rapid diagnosis, Dr Hazra’s group has developed a novel kit to detect the presence of Beta-lactamase enzymes in bacteria. This kit has now been patented. It promises to cut down diagnosis time to minutes, reducing weeks of patient suffering. He has also developed and patented kits to detect AMR load in environmental samples. So that AMR monitoring can take place at an industrial scale.
He sagely confesses that the AMR problem can’t be addressed by just one approach. Scientists from various backgrounds must engage in an interdisciplinary collaboration to ensure that we have a fighting chance against this silent pandemic. We thank Dr. Hazra for coming on our platform to share his deep expertise with us.
You can access the 90+ minute discussion with him through the link below.
Written by Deven Matkari
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