The battle against superbugs

Bengaluru-based labs and start-ups are attempting to design molecules that can be developed into broad-spectrum drugs to combat drug-resistant bacteria.

“With drug-discovery pipelines drying out, a new molecule that can bedeployed against pathogens has become the holy grail in the pharmaceutical arena.” PHOTO: SPECIAL ARRANGEMENT

The sugar-loving Klebsiella pneumoniae , that resembles a squished-up earplug, can strike fear into the hearts of surgeons and scientists. The bacterium can repel even the most powerful antibiotics. It has pumps that can eject most antibiotics that breach its cell wall. More worryingly, this pathogen has begun producing an enzyme that renders a sophisticated class of antibiotics called carbapenems useless.

Healthy people usually don’t get Klebsiella infections, but its presence in an ICU can be a harbinger of death for immune-compromised patients. “When the bacteria enter the bloodstream, doctors stand by helplessly as a patient dies of multiple organ failure,” says microbiologist Dr. V. Balasubramanian.

The holy grail of pharma

A project commissioned by the U.K. government recently announced that drug-resistant bacteria — or their more evocative moniker, superbugs — will cause 10 million deaths per year by 2050. With drug-discovery pipelines drying out, a new molecule that can be deployed against pathogens such as

Klebsiella pneumoniae has become the holy grail in the pharmaceutical arena.

Dr. Balasubramanian is on one such mission. The founder of Bugworks, a Bengaluru-based start-up, is attempting to design molecules that can effectively be developed into broad-spectrum drugs, which work on bacteria like

Klebsiella . The team at Bugworks claims to have made some headway in overcoming the challenges presented by gram-negative bacteria, a group of bacteria (including Klebsiella ) with greater resistance to drugs. “The biggest challenge in gram negatives has been efflux pumps, which basically throw out anything that comes in. We think we have cracked a methodology by which we can overcome the pumps,” says Dr. Balasubramanian.

Bugworks operates out of the Centre for Cellular and Molecular Platforms (C-Camp) — a not-for-profit Department of Biotechnology start-up incubator — and shares a campus with the National Centre for Biological Sciences. Both organisations are part of the Bangalore Life Sciences Cluster.

Long-drawn-out war

Several scientists at NCBS like Dr. Aswin Sai Narain Seshasayee, who heads a computational research lab, Bugbears, are on the bacterial trail. “In a lab setting, I have seen bacteria develop resistance to a new molecule in a few hours,” says Seshasayee, likening the situation to a long-drawn-out war that “will have us look to the future for new ways to win the battle”.

The team at Bugworks sees itself on the frontline of this war. But can a start-up play in an arena dominated by big pharma? “Our focus is on designing the molecule. Everything else is done through a network of contracts,” says CEO and MD of Bugworks, Anand Anandkumar.

Perhaps pared-down start-ups, free of red tape, may just have that disruptive edge. “We can do it. Bacteria have been producing antibiotics for three billion years,” says Dr. Mukund Thattai, physicist-turned-biologist at NCBS.

In the microbial world, bacteria often develop molecules against each other. This is the source of the antibiotics we use. “But just because you’ve made a new antibiotic, it doesn’t mean it’s going to be useful forever,” says Dr. Thattai. He suggests that instead of copying the molecule, we copy the process that bacteria use to make that molecule. “Bacteria have developed a sort of protein assembly line, like a factory. The pathways were not designed to make a single product, but different products,” he says, using the analogy of an assembly line that can make a car and also be turned around to make a toaster with minimal effort.

Now that would be a better weapon in a war with no permanent solution. Where all gains are temporary and where, as Dr. Thattai puts it, only evolution can be pitted against evolution.

anjali.thomas@thehindu.co.in