If the world doesn’t watch out, bacteria that just a few years ago were held at bay by antibiotics could reassert themselves in an aggressive and deadly manner. Drug-resistant bacteria are already responsible for hundreds of thousands of deaths, and that could climb to millions in the coming decade if something isn’t done.
So far, the response of science has been to develop ever-stronger antibiotics. But researchers at Tel Aviv University believe they have a solution that will be a lot more effective in the long run. The TAU solution uses fire to fight fire – inserting a virus that makes the antibiotic-resistant bacteria “sick” and weak enough to be killed off by drugs.
In a paper published last month in the Proceedings of the National Academy of Sciences, Prof. Udi Qimron and a team from the Department of Clinical Microbiology and Immunology at TAU’s Sackler Faculty of Medicine showed how a bacteriophage – a virus that infects and replicates within a bacterium – changes the DNA of bacteria, crippling the activity of a protein that allows it to maintain its cell structure. Without that protein, the bug essentially collapses on itself. It’s destroyed completely, or becomes easy pickings for current antibiotics.
According to UK scientists, within a few decades drug-resistant bacteria will kill more people annually than cancer, and cost society $100 trillion a year. Among scientists, it is generally agreed that the reason for this has been, at least in part, the overuse of antibiotics in humans, and especially in animals, which are given antibiotics even when they are not sick on the theory that such treatments will keep them healthy enough to make it through their life cycle without illness. While many of the bugs are killed in this manner, some survive – and those that do pass on their resistance. When those animals – chicken or cows, for example, or their products, eggs and milk – come to market, they may contain some of those resistant bacteria, researchers believe. Antibiotic waste in the environment, from humans, animals, and the pharmaceutical industry could also be contributing to the problem.
Whatever the reason, the rise of the superbugs is a growing problem, according a UK-sponsored project called the Review on Antimicrobial Resistance, which says that drug-resistant bugs are already responsible for over 700,000 deaths worldwide annually – a number that could grow to 10 million by 2050. Dealing with the problem could cost $100 trillion – as much as 3.5% of the world’s GDP – and that doesn’t include secondary and tertiary costs (i.e., losses due to the expected death of nightlife, as people avoid restaurants and the movies because of the pandemics that will become common).
As a result, scientists have made finding ways to battle the superbugs a top priority. At Tel Aviv University, the team led by Prof. Qimron discovered an Achilles’ heel in these creatures that can be exploited to fight them.
Using high-throughput DNA sequencing, the researchers identified a new small protein, growth inhibitor gene product (Gp) 0.6, which specifically targets and inhibits the activity of a protein essential to bacterial cells. By inserting a phage, the key cytoskeleton protein was impaired, resulting in the rupture and consequent death of the bacterial cell. “Strikingly,” the study said “in over 70 years of extensive research into the tested bacteriophage, this inhibition had never been characterized.”
“Because bacteria and bacterial viruses have co-evolved over billions of years, we suspected the viruses might contain precisely the weapons necessary to fight the bacteria,” Prof. Qimron said. “So we systematically screened for such proteins in the bacterial viruses for over two and a half years.”
The study included several specific bacteria and phages, but with the structure of many other bacteria similar, it is highly likely that the same method will work with other superbugs, said the team.
“We believe that the presented approach may be broadened to identify novel, clinically relevant bacteriophage growth inhibitors and to characterize their targets. The new technology and our new interdisciplinary collaboration, drawing from bioinformatics and molecular biology, promoted our study more than we could have anticipated,” said Prof. Qimron. “We hope our approach will be used to further identify new growth inhibitors and their targets across bacterial species and in higher organisms.”