In his lab at United Arab Emirates University in Al-Ain, John Michael Conlon collects the secretions that ooze out of frog skins. Over the past 12 years, he’s collected hundreds of samples from frogs all around the world (the one Canadian frog in his collection is the wood frog). Conlon’s hoping to find an antibiotic that could fight off powerful “superbugs,” bacteria that our current drugs can’t beat. Frogs have spent millions of years evolving to fight off microbes, he explains: they live in a moist, warm environment, “an ideal place for the growth of bacteria and fungi.” After analyzing just 200 secretions, Conlon’s team has found over 100 antimicrobial substances.
With drug-resistant bacteria on the rise, they can’t work fast enough. Last month, The Lancet Infectious Diseases journal published a study showing that NDM-1, a gene that makes bacteria impervious to some of our strongest antibiotics and can jump from one bacterial strain to another, has the potential to become a global health problem. Thought to have originated in India, NDM-1 positive bacteria has already turned up in several countries, including Canada. Other superbugs, like MRSA (a staph bacteria that resists the methicillin antibiotic), are also a growing concern. “I’m English, and English people tend to deal in understatements, not exaggerations,” Conlon says dryly. “This situation really is serious.”
Conlon’s work with frog skin may sound unusual, but many of our antibiotics are naturally derived (penicillin comes from a mould), since bacteria and other organisms have been “duking it out for millions of years,” says Ramanan Laxminarayan, director and senior fellow at the Center for Disease Dynamics, Economics & Policy in Washington. Last week, scientists from the University of Nottingham announced that cockroach brains could make powerful antibiotics; they contain substances that seem to kill off MRSA. Working with secretions of the foothill yellow-legged frog, which is facing extinction, Conlon’s isolated a substance that shows promise for treating MRSA, too. Another, from the mink frog, might be able to fight off so-called “Iraqibacter” (multi-drug-resistant Acinetobacter baumannii), infecting soldiers returning from Iraq.
Another source might be lichen, a fungus that grows symbiotically with an alga. Lichen fungi grow more slowly than bacteria, explains John Sorensen of the University of Manitoba, but compete fiercely with them for resources, producing chemicals to fend them off. Michele Piercey-Normore, his colleague, travels by helicopter to northern Manitoba, where lichen “grow big and luscious” on peat that covers the permafrost since there aren’t any plants around to compete with, she says. She brings her samples back to the university, where collaborators check for antibiotic activity. “Our goal is to find something useful against resistant strains of bacteria, like NDM-1,” Sorensen says. “We’re looking for a new class of antibiotics. We would win no prizes for finding more penicillin.”
Research of this kind is gruellingly slow. The pair have been working together for a few years, and hope to identify tangible leads within a few more. But even after finding a molecule that appears to kill off bacteria, bringing a drug to market costs “hundreds of millions,” and can take years, Conlon says, noting that drug companies have largely stopped investing in antibiotics, turning to more lucrative drugs instead. As a result, he says, “there are no very good new antibiotics in the pipeline.”
And bacteria are a fast-moving target. In the 60-odd years antibiotics have been widely available, we’ve come to depend on them for everything from treating infection to prophylactic use before long surgeries. With increasing use, “resistance has been developing, like a pot on slow boil,” says Laxminarayan.
Over-prescription is one problem, and when patients stop taking a dose midway, weaker bugs are knocked out, leaving stronger ones behind to be passed along. “Any action that contributes to drug-resistant bacteria within ourselves means we’re more likely to transmit it to other people,” he says. The rising use of antibiotics in developing countries could impact drug resistance worldwide, too, he notes. Evolution among bacteria occurs at an alarming rate. In one day, they can make up to 40 generations, developing new tricks to evade antibiotics, says the University of Saskatchewan’s David Sanders.
Without prevention, new antibiotics aren’t enough. Here, too, the Canadian North offers some help. In his lab, University of Victoria microbiologist Francis Nano has got a freezer full of bacteria, some of it scraped from underneath an ice shelf in Canada’s high Arctic. When his colleagues travel up north, “I often sterilize a couple of metal thermoses with alcohol and give them to them,” he says. These bacteria can’t function at high temperatures; some die off at just 12° C. Cold-loving bacteria could be used to make temperature-sensitive bacterial vaccines, safe at human body temperature.
Finding new antibiotics is a daunting task. “Resistance is inevitable,” says Eric Brown, chair of the biochemistry and biomedical sciences department at McMaster University. “But the work can’t stop. It’s got to keep going. I think history’s proven that.”