US scientists have found that a small minority of highly antibiotic-resistant bacteria will produce and share a molecule, indole, that can activate survival mechanisms in less-resistant cells to enable the whole bacterial population to survive stressful environments despite the fact that production of this signalling molecule weakens the fitness of bacteria.
The increasing incidence of antibiotic resistance and the emergence of so-called ‘superbugs’ are of huge importance to medicine and society as a whole with the ever-increasing likelihood of a return to a world without antibiotics. This potentially disastrous public health crisis led the Infectious Diseases Society of America to launch the “10x’20” initiative in which they call for a global commitment to research and develop 10 new, effective antibiotic drugs by 2020. As a complement to this drug development, research into how bacteria develop this resistance could provide crucial clues for the rational design of new antimicrobial agents.
Henry Lee and colleagues investigated the population dynamics of antibiotic resistance. They grew a vat of E. coli with increasing amounts of the antibiotic norfloxacin and then took samples of the bacteria and monitored the percentage of bacteria that became resistant to the antibiotic. The scientists found an individual isolate that was highly resistant to norfloxacin (even higher than the greatest norfloxacin levels tested in their bioreactor). These bacteria produced indole, which is known to aid tolerance to stress in E. coli—indole induces anti-stress mechanisms such as drug efflux pumps that help drive out toxic substances from the bacterial cell—although its production can reduce the overall fitness of the bacteria. Moreover, indole boosts the antibiotic resistance of the whole bacterial population and not just the select few that produce it. This population-based resistance was not drug specific and was even observed when the scientists challenged E. coli with gentamicin, which is a different type of antibiotic (with a different mode of action) to the quinolone norfloxacin.
The researchers conclude that under antibiotic stress, a few drug-resistant mutants will endure a fitness cost to produce and share the benefits of the metabolite indole to “shield the less-resistant bacteria from antibiotic insult” and enable these ‘weak’ bacteria to survive.
Lee HH, Molla MN, Cantor CR, & Collins JJ (2010). Bacterial charity work leads to population-wide resistance. Nature, 467 (7311), 82-5 PMID: 20811456