Assembly and Functional Role of PACE Transporter PA2880 from Pseudomonas Aeruginosa

Overview

Journal Microbiol Spectr

Specialty Microbiology

Date 2022 Apr 4

PMID 35377188

Authors

Jiangfeng Zhao

Nils Hellwig

Bardya Djahanschiri

Radhika Khera

Nina Morgner

Ingo Ebersberger

Jingkang Wang

Hartmut Michel

Affiliations

Soon will be listed here.

Abstract

The recently identified proteobacterial antimicrobial compound efflux (PACE) transporters are multidrug transporters energized by the electrochemical gradient of protons. Here, we present the results of phylogenetic and functional studies on the PACE family transporter PA2880 from Pseudomonas aeruginosa. A phylogenetic analysis of the PACE family revealed that PA2880 and AceI from Acinetobacter baumannii are classified into evolutionarily distinct clades, although they both transport chlorhexidine. We demonstrate that PA2880 mainly exists as a dimer in solution, which is independent of pH, and its dimeric state is essential for its proper function. Electrogenicity studies revealed that the chlorhexidine/H antiport process is electrogenic. The function of several highly conserved residues was investigated. These findings provide further insights into the functional features of PACE family transporters, facilitating studies on their transport mechanisms. Pseudomonas aeruginosa is a pathogen that causes hospital-acquired (nosocomial) infections, such as ventilator-associated pneumonia and sepsis syndromes. Chlorhexidine diacetate is a disinfectant used for bacterial control in various environments potentially harboring P. aeruginosa. Therefore, investigation of the mechanism of the efflux of chlorhexidine mediated by PA2880, a PACE family transporter from P. aeruginosa, is of significance to combat bacterial infections. This study improves our understanding of the transport mechanism of PACE family transporters and will facilitate the effective utilization of chlorhexidine for P. aeruginosa control.

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