Some bacteria are able to avoid antibiotics just by being lazy: the bacteria lack the energy to ingest drugs as they enter a system. Dubbed “persisters,” these bacteria are distinct from those that mutate and gain resistance to antibiotics through a range of other defenses. In the presence of stressors, such as antibiotics, persister bacteria slow their metabolism and become semi-dormant. In this state they are able to tolerate antibiotic treatment, later re-activating and proliferating, causing chronic and recurring infections. These bacteria are a particular problem in biofilms—highly resistant infections commonly formed around surgical implants.
We may soon be able to force these bacteria out of their slothful state. Professor James Collins and his lab found stimulating the metabolism of persisters can energize them enough to consume and be killed by antibiotics. EnBiotix, a company co-founded by Collins, now has two drugs in clinical trials utilizing this metabolite-antibiotic combination—one targeting catheter-associated urinary tract infections and one targeting Pseudomonas aeruginosa in cystic fibrosis patients.
In preliminary studies in mice, adding metabolites to aminoglycoside antibiotics reduced the bacterial load on catheters infected with E. coli by one and half times. In the laboratory adding a metabolite to tobramycin resulted in a four-log improvement over use of tobramycin alone against P. aeruginosa, and the results were similar in animal models.
Molly Miller-Petrie is a Senior Research Analyst at CDDEP.
Images courtesy EnBiotix.