September 17, 2020

Probing pathogen antibiotic resistance

Understanding how bacteria evolve resistance to antibiotics and host stresses could guide the development of more effective antimicrobial therapeutics.

by Leigh MacMillan

Acinetobacter baumannii — a leading cause of ventilator-associated pneumonia — is becoming more prevalent and resistant to antibiotics. 

The outer membrane of A. baumannii and other Gram-negative bacteria provides a barrier against host and antibiotic stresses and is maintained by the Mla system, which has been proposed as a target for antimicrobial drug development. 

Eric Skaar, PhD, MPH, and colleagues studied the Mla system in A. baumannii in a mouse model of pneumonia. They showed that disruption of the Mla system made A. baumannii more susceptible to pulmonary surfactants and antibiotics and decreased bacterial survival. 

The investigators isolated strains of A. baumannii missing the Mla system that were still able to infect mouse lungs, and they characterized a spontaneous genetic insertion that affects membrane component biosynthesis. They found the same insertion in an extensively drug-resistant clinical strain of A. baumannii. 

The findings, published in Cell Reports, demonstrate that A. baumannii rapidly evolves resistance to antibiotics and host stressesincluding by modulating the outer membrane.

This research was supported by the National Institutes of Health (grants AI101171, HL094296, AI122516, HL143441, GM010344, AI139248, AI138581, DK058404). Additional funding was provided by the Ernest W. Goodpasture professorship to Skaar and the Parker B. Francis fellowship program to first author Lauren Palmer.