New Study Reveals How Drug Resistance Could Advance Antibiotic Therapies

A new study from e-Life provides insight into the evolution of antibiotic resistance in a type of bacterium that causes severe infections in humans, which could potentially lead to advancements in antibiotic therapies.

Published on Oct. 29, 2019, the study focuses on the multidrug-resistant bacterium Pseudomonas aeruginosa (P. aeruginosa) and how it can be used to develop new and sustainable antibiotic treatments, according to a press release.

“The World Health Organization warns of a post-antibiotic era in which infections can no longer be treated and could become one of the most frequent non-natural causes of death,” said first author Camilo Barbosa, a former postdoctoral student at the Kiel Evolution Center of Kiel University, Germany. “The rapid evolution of antibiotic resistance makes antibacterial drugs ineffective within short periods of time, which means we need new strategies to maintain or even improve the effectiveness of existing antibiotics. But this development needs to take the relevant evolutionary processes into account, or else new drugs will likely fail.”

According to the release, researchers studied collateral sensitivity in P. aeruginosa, which occurs when bacteria develop resistance to one drug but develop sensitivity to another drug simultaneously.

“While a variety of distinct cases of collateral sensitivities have previously been described, it was still unclear whether they could be exploited for antibiotic treatment,” Barbosa said. “We tested one key requirement of this principle for medical implementation: stability of the evolutionary trade-off. Is collateral sensitivity stable across time, thereby allowing us to exploit it as a trade-off in order to eliminate bacterial populations and/or prevent the emergence of drug resistance?”

The researchers came to the conclusion that P. aeruginosa developed sensitivities in response to various drugs, which can potentially lead to population extinction or an absence of the evolution of multidrug resistance. They also discovered the impact of the drugs was determined by the order they were used in, the evolutionary costs for the bacteria when evolving antibiotic resistance, and the underlying genetic mechanisms.

“The pathogen’s ability to adapt was particularly constrained when the treatment included a drug change from an aminoglycoside to a beta-lactam, a penicillin-like substance," Barbosa said. “In this case, the bacteria were unable to adapt and went extinct as a result of the sequential administration of the antibiotics. In other drug combinations, however, the pathogens were able to develop new multiple resistances. The evolutionary costs of resistance to the bacteria also played an important role in therapy success.”

Source: e-Life