Pan-Genome Plasticity and Virulence Factors: A Natural Treasure Trove for Acinetobacter baumannii

Abstract

Acinetobacter baumannii is a Gram-negative pathogen responsible for a variety of community- and hospital-acquired infections. It is recognized as a life-threatening pathogen among hospitalized individuals and, in particular, immunocompromised patients in many countries. A. baumannii, as a member of the ESKAPE group, encompasses high genomic plasticity and simultaneously is predisposed to receive and exchange the mobile genetic elements (MGEs) through horizontal genetic transfer (HGT). Indeed, A. baumannii is a treasure trove that contains a high number of virulence factors. In accordance with these unique pathogenic characteristics of A. baumannii, the authors aim to discuss the natural treasure trove of pan-genome and virulence factors pertaining to this bacterial monster and try to highlight the reasons why this bacterium is a great concern in the global public health system.

Keywords: Acinetobacter baumannii; genome; molecular pathogenicity; plasticity; virulence factors.

Figure 2

A schematic bacterial cell pertaining to Acinetobacter baumannii. The situation and structures of important virulence factors include the capsule, outer membrane proteins (Omps), lipopolysaccharide (LPS), Csu pilus, type IV pilus, efflux pumps and secretion systems (SSs). As shown, the secretion systems exert molecules (proteins) into the extracellular zone. Two types of T5bSS and T5cSS have been detected in A. baumannii. Although there are five sub-groups of T5SS (e.g., T5aSS, T5bSS, T5cSS, T5dSS and T5eSS) in Gram-negative bacteria, only two sub-groups of T5bSS and T5cSS are detected among the A. baumannii strains. Among these two secretion systems, T5cSS is the main secretion system that can be identified in A. baumannii populations. The efflux pumps—excluding ABC and RND families—take protons from the bacterial periplasm space into the cytoplasm and simultaneously excrete antibiotics from the bacterial cytoplasm into the periplasm space. The ABC family consumes ATP to excrete the antibiotic molecules from the bacterial periplasm space into the extracellular space. It acts as uniport efflux pump. On the other hand, the RND family takes the protons from the periplasm space into the cytoplasmic space and simultaneously excretes the antibiotic molecules from the periplasm space into the extracellular space [68,80,86].

Figure 1

The main antibiotic resistance mechanisms can be divided into three categories in A. baumannii. In this regard, LPS modification or mutation in LPS bisynthesis genes, efflux pumps (promoted efflux), outer membrane proteins (OMPs/porins) (decrease in OMPs’ permeability) and secretion systems (T2SS, T4SS and T6SS) contribute to antibiotic resistance through transportation via bacterial cell membranes; antibiotic inactivation via enzymes (e.g., monooxygenase and β-lactamase enzymes); alterations and modifications in antibiotic target sites, such as mutations in antibiotic target enzymes (including DNA gyrase (single mutations in parC (topoisomerase IV encoding gene)) and/or in gyrA (DNA topoisomerase IV encoding gene) against fluoroquinolones), mutations in Penicillin-binding proteins (PBPs)), ribosomal protection proteins (RPPs) in the occurrence of non-covalent modifications of bacterial ribosomes against antibiotics (e.g., tetracycline), production of ribosome methylase enzymes (via plasmid-transposon-borne genes) against lincosamides, and 16S rRNA methylase enzymes against aminoglycosides. Plasmids are important MGEs directly participating in antibiotic-resistant genes via HGTs [3,62,63,64,65].