Saturday, 9 February 2019

New strategy to curtail spread of antibiotic resistance


Researchers at Washington University School of Medicine in St. Louis have figured out a key step in the transmission of antibiotic resistance from one Acinetobacter bacterium to another, insight that sheds light on how antibiotic resistance spreads through a hospital or community. This could open up a new strategy to safeguard our ability to treat bacterial infections with antibiotics. The research indicates that the effectiveness of current antibiotics may be somewhat preserved by curtailing the spread of antibiotic-resistance genes.

Spotless surfaces in hospitals can hide bacteria that rarely cause problems for healthy people but pose a serious threat to people with weakened immune systems. Acinetobacter baumannii causes life-threatening lung and bloodstream infections in hospitalized people. Such infections are among the most difficult to treat because these bacteria have evolved to withstand most antibiotics.

Acinetobacter strains carry the genetic blueprints for drug resistance on small loops of DNA called plasmids that come in two sizes. Big plasmids, which are prone to accumulating ever more antibiotic-resistance genes, carry the genetic instructions to build a needle-like appendage to insert copies of themselves into nearby bacteria. Small plasmids, which contain resistance genes against a single but important group of antibiotics known as carbapenems, lack their own distribution tools so they invade new bacteria by tagging along with the large plasmids.

The plasmids' reproductive strategy requires close contact between two bacteria. But that raises a question: How do two bacteria ever get near enough to transmit plasmids to each other? Most Acinetobacter guard against strangers with a system that injects lethal proteins into any unrelated bacteria that approach too closely, thus reducing the changes of spreading antibiotic-resistance genes.

The researchers found that plasmids disable bacteria's self-defense systems so that plasmids can inject copies of themselves into neighboring bacteria, conferring drug resistance on the unwitting bacterial neighbors. By forcing the bacteria in which they reside to lay down their weapons, the plasmid ensures that nearby bacteria aren't killed before the plasmids can infect them. The researchers found that mutating plasmids so they could not interfere with the bacteria's defenses - or mutating the bacteria so the defenses could not be lowered -- prevented plasmids from spreading.


These findings provide a novel opening to interrupt the spread of drug resistance, the researchers said. The genes involved have been identified. Now researchers have to find compounds that prevent plasmids from disrupting bacterial-defense systems.

See:

Gisela Di Venanzio, Ki Hwan Moon, Brent S. Weber, Juvenal Lopez, Pek Man Ly, Robert F. Potter, Gautam Dantas, Mario F. Feldman. Multidrug-resistant plasmids repress chromosomally encoded T6SS to enable their dissemination. Proceedings of the National Academy of Sciences, 2019; 201812557 DOI: 10.1073/pnas.1812557116

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

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