Contribution of the Ade Resistance-Nodulation-Cell Division-Type Efflux Pumps to Fitness and Pathogenesis of Acinetobacter baumannii

Abstract

Overproduction of the RND AdeABC efflux system is observed with a high incidence in multidrug-resistant Acinetobacter baumannii and results in increased resistance to several antibiotics of choice for the treatment of infections caused by this nosocomial pathogen. It was therefore important to study the biological cost of the overexpression of the adeABC structural operon which is normally tightly regulated. Fitness diminution of an overexpressing mutant detected in vitro and in vivo in a model that mimics sepsis was not observed in a pulmonary infection model in which the mutant was more virulent. This points out that increased virulence can occur independently from prolonged persistence in the infected organ and can account for the elevated incidence of this resistance mechanism in clinical isolates. The study also indicates that transposon libraries will identify only virulence genes that are expressed under physiological conditions but not those that are tightly regulated.