Impact of environmental conditions on expression levels of resistance-nodulation-division (RND) efflux pumps and outer membrane porins in Acinetobacter baumannii

Abstract

Acinetobacter baumannii is a globally emerging Gram-negative pathogen accounting for a variety of nosocomial conditions, including pneumonia, meningitis, peritonitis, urinary tract infections and, in particular, wound infections in soldiers. One of the major reasons for A. baumannii success as a human pathogen is attributed to a tremendous potential of this organism for development of the multidrug resistant phenotype (MDR). This organism’s ability to regulate expression of its intrinsic antibiotic resistance determinants, such as Resistance-Nodulation-Cell Division (RND) efflux pumps and outer membrane proteins, is regarded to be amongst the most important strategies in the arsenal of this pathogen. Despite considerable efforts being dedicated in the attempt to understand the underlying mechanisms in the development of the MDR phenotype in A. baumannii, the role of environmental stress factors is often overlooked. Evidence from other Gram-negative pathogens suggests that adaptive responses of the bacterial cell to environmental stress often target the same cellular processes that are exploited by antibiotics, therefore indirectly promoting the emergence of the MDR phenotype. This study shows the impact of a variety of environmental factors, namely iron(III) availability, oxidative stress, salicylate exposure, steady-state osmotic stress, ethanol shock, exposure to different incubation temperatures and exposure to blue light on expression levels of three RND efflux pumps and three outer membrane porins of A. baumannii. In addition, we investigated the difference in expression levels of the selected two-component systems between a type strain of A. baumannii, ATCC 19606, and two clinical isolates with the MDR and biofilm-forming phenotypes. The quantitative-real time polymerase chain reaction analysis revealed that levels of iron(III) in growth medium, oxidative stress and ethanol shock were amongst the most potent factors capable of influencing expression of RND efflux pumps and outer membrane porins.