Abstract

Carbapenem-resistant Acinetobacter baumannii strains cause life-threatening infections due to the lack of therapeutic options. Although the main mechanisms underlying antibiotic-resistance have been extensively studied, the general response to maintain bacterial viability under antibiotic exposure deserves to be fully investigated. Since the periplasmic space contains several proteins with crucial cellular functions, besides carbapenemases, we decided to study the periplasmic proteome of the multidrug-resistant (MDR) A. baumannii AB5075 strain, grown in the absence and presence of imipenem (IMP). Through the proteomic approach, 65 unique periplasmic proteins common in both growth conditions were identified: eight proteins involved in protein fate, response to oxidative stress, energy metabolism, antibiotic-resistance, were differentially expressed. Among them, ABUW_1746 and ABUW_2363 gene products presented the tetratricopeptide repeat motif, mediating protein-protein interactions. The expression switch of these proteins might determine specific protein interactions to better adapt to changing environmental conditions. ABUW_2868, encoding a heat shock protein likely involved in protection against oxidative stress, was upregulated in IMP-exposed bacteria. Accordingly, the addition of periplasmic proteins from A. baumannii cultured with IMP increased bacterial viability in an antioxidant activity assay. Overall, this study provides the first insights about the composition of the periplasmic proteins of a MDR A. baumannii strain, its biological response to IMP and suggests possible new targets to develop alternative antibiotic drugs.

Highlights

  • Acinetobacter baumannii is a non-fermentative Gram-negative coccobacillus, commonly found in water, soil and normal flora of humans [1,2]

  • Since the periplasmic space contains several proteins with crucial cellular functions, besides carbapenemases, we decided to study the periplasmic proteome of the multidrug-resistant (MDR) A. baumannii AB5075 strain, grown in the absence and presence of imipenem (IMP)

  • This study provides the first insights about the composition of the periplasmic proteins of a MDR A. baumannii strain, its biological response to IMP and suggests possible new targets to develop alternative antibiotic drugs

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Summary

Introduction

Acinetobacter baumannii is a non-fermentative Gram-negative coccobacillus, commonly found in water, soil and normal flora of humans [1,2]. Considered a low virulent microorganism, the A. baumannii group has become one of the most concerning opportunistic pathogens in health-care settings worldwide, accounting for approximately 90–95% of clinical infections and nosocomial outbreaks (www.who.int; www.ecdc.europa.eu). The exceptional advantage of A. baumannii over other nosocomial microorganisms is its ability to persist on medical device and equipment surfaces and rapidly develop resistance to most or all available antibiotics [1,2]. The resistance to carbapenems is often conferred by a decreased influx and/or increased antibiotic efflux. The decreased outer membrane (OM) permeability is achieved by under-expression of porins involved in the antibiotic influx and increased drug efflux by efflux pumps [2]. The efflux pump mainly associated with carbapenem efflux is the three-component AdeABC pump (for Acinetobacter drug efflux), belonging to the resistance-nodulation-division (RND) superfamily [5]. In multidrug-resistant (MDR) A. baumannii strains, β-lactamases reside within the periplasmic space [6]

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