Abstract

Acinetobacter baumannii has emerged as one of the most problematic bacterial pathogens responsible for hospital-acquired and community infections worldwide. Besides its high capacity to acquire antibiotic resistance mechanisms, it also presents high adhesion abilities on inert and living surfaces leading to biofilm development. This lifestyle confers additional protection against various treatments and allows it to persist for long periods in various hospital niches. Due to their remarkable antimicrobial tolerance, A. baumannii biofilms are difficult to control and ultimately eradicate. Further insights into the mechanism of biofilm development will help to overcome this challenge and to develop novel antibiofilm strategies. To unravel critical determinants of this sessile lifestyle, the proteomic profiles of two A. baumannii strains (ATTC17978 and SDF) grown in planktonic stationary phase or in mature solid–liquid (S-L) biofilm were compared using a semiquantitative proteomic study. Of interest, among the 69 common proteins determinants accumulated in the two strains at the S-L interface, we sorted out the MacAB-TolC system. This tripartite efflux pump played a role in A. baumannii biofilm formation as demonstrated by using ΔmacAB-tolC deletion mutant. Complementary approaches allowed us to get an overview of the impact of macAB-tolC deletion in A. baumannii physiology. Indeed, this efflux pump appeared to be involved in the envelope stress response occurring in mature biofilm. It contributes to maintain wild type (WT) membrane rigidity and provides tolerance to high osmolarity conditions. In addition, this system is probably involved in the maintenance of iron and sulfur homeostasis. MacAB-TolC might help this pathogen face and adapt to deleterious conditions occurring in mature biofilms. Increasing our knowledge of A. baumannii biofilm formation will undoubtedly help us develop new therapeutic strategies to tackle this emerging threat to human health.

Highlights

  • Over the last decades, Acinetobacter baumannii has emerged as one of the most problematic opportunistic pathogens involved in hospital-acquired infections and community infections worldwide (Lin and Lan, 2014)

  • The proteomic quantitative study revealed that among the 1,523 and 1,114 unique proteins identified in the overall samples from ATCC 17978 and SDF, respectively (Figure 1A), 477 and 403 proteins showed a significant variation of abundance according to the mode of growth [Supplementary Table 3 (ATCC) and Supplementary Table 4 (SDF)]

  • A. baumannii S-L biofilms were characterized by decreased accumulation of proteins involved in bacterial fitness including metabolic proteins and in important surface remodeling such as membrane proteins belonging to transport systems

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Summary

Introduction

Acinetobacter baumannii has emerged as one of the most problematic opportunistic pathogens involved in hospital-acquired infections and community infections worldwide (Lin and Lan, 2014). Its high capacity to acquire antibiotic resistance mechanisms has led to the increasing occurrence of outbreaks of infection involving multior pan-drug-resistant A. baumannii (Lee et al, 2017; Nasr, 2020) It presents remarkable adhesion abilities on inert and leaving surfaces, leading to biofilm development that allows it to survive desiccation (Gayoso et al, 2014), oxidative stress (Soares et al, 2010), or disinfectants (Peleg et al, 2008; Harding et al, 2018) and to persist for long periods in various hospital environments. The pathogenic potential of sessile microorganisms is much higher than the one of planktonic cells

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