The Tol-Pal system of Acinetobacter baumannii is important for cell morphology, antibiotic resistance and virulence

Abstract

Acinetobacter baumannii is an opportunistic human pathogen that has become a global threat to healthcare institutions. This Gram-negative bacterium is one of the most successful human pathogens worldwide and responsible for hospital-acquired infections. This is due to its outstanding potential to adapt to very different environments, to persist in the human host and most important, its ability to develop multidrug resistance. Our combined approach of genomic and phenotypic analyses led to the identification of the envelope spanning Tol-Pal system in A. baumannii. We found that the deletion of the tolQ, tolR, tolA, tolB, and pal genes affects cell morphology and increases antibiotic sensitivity, such as the ∆tol-pal mutant exhibits a significantly increased gentamicin and bacitracin sensitivity. Furthermore, Galleria mellonella caterpillar killing assays revealed that the ∆tol-pal mutant exhibits a decreased killing phenotype. Taken together, our findings suggest that the Tol-Pal system is important for cell morphology, antibiotic resistance, and virulence of A. baumannii.

Mechanism of Tol/Pal System in Antibacterial Therapies

“…(1) Acinetobacter baumannii It provides intrinsic resistance to antibiotics and detergents (sodium dodecyl sulfate) by reducing membrane permeability and maintaining membrane integrity. 58 (2) Burkholderia cenocepacia It causes bacterial adaptation and, in turn, its survival in the lungs by improving attachment to lung epithelial cells and inflammation during cystic fibrosis infections. 59 (3) Citrobacter rodentium Enteritis and lethality in mice are associated with tolB, contributing to cell motility, adherence to host cells, and secretion of the proteins EspA/B from the Type III secretion system.…”

Domain-architecture aware phylogenetic profiling indicates a functional diversification of type IVa pili in the nosocomial pathogenAcinetobacter baumannii

“…The world-wide spread of multi-or even pan-resistant A. baumannii isolates [4][5][6] is accompanied by a surge in virulence [6][7][8][9][10], and thus novel therapeutic treatments are necessary for a sustainable infection management. Over the past years, experimental studies integrated with comparative genomics analyses have therefore sought to identify genetic determinants of A. baumannii virulence [11][12][13][14][15][16][17][18][19][20][21][22][23]. The identified factors are involved into a broad spectrum of biological processes including NOS and ROS resistance and metabolic adaptation, but some also indicate changes in the way how the pathogen interacts with its environment [17,20].…”

Feature architecture aware phylogenetic profiling indicates a functional diversification of type IVa pili in the nosocomial pathogen Acinetobacter baumannii

“…The spread of multi-or even pan-resistant A. baumannii isolates [2][3][4] is accompanied by a surge in virulence [4][5][6][7][8], and thus novel therapeutic treatments are necessary for sustainable infection management. Over the past years, experimental studies integrated with comparative genomics analyses have sought to identify genetic determinants of A. baumannii virulence [9][10][11][12][13][14][15][16][17][18][19][20][21]. The resulting candidates are involved in a broad spectrum of biological processes including NOS and ROS resistance and metabolic adaptation, but some also indicate changes in the way the pathogen interacts with its environment [15,21].…”