Small, Enigmatic Plasmids of the Nosocomial Pathogen, Acinetobacter baumannii: Good, Bad, Who Knows?

Abstract

Acinetobacter baumannii is a Gram-negative nosocomial pathogen that has become a serious healthcare concern within a span of two decades due to its ability to rapidly acquire resistance to all classes of antimicrobial compounds. One of the key features of the A. baumannii genome is an open pan genome with a plethora of plasmids, transposons, integrons, and genomic islands, all of which play important roles in the evolution and success of this clinical pathogen, particularly in the acquisition of multidrug resistance determinants. An interesting genetic feature seen in majority of A. baumannii genomes analyzed is the presence of small plasmids that usually ranged from 2 to 10 kb in size, some of which harbor antibiotic resistance genes and homologs of plasmid mobilization genes. These plasmids are often overlooked when compared to their larger, conjugative counterparts that harbor multiple antibiotic resistance genes and transposable elements. In this mini-review, we will examine our current knowledge of these small A. baumannii plasmids and look into their genetic diversity and phylogenetic relationships. Some of these plasmids, such as the Rep-3 superfamily group and the pRAY-type, which has no recognizable replicase genes, are quite widespread among diverse A. baumannii clinical isolates worldwide, hinting at their usefulness to the lifestyle of this pathogen. Other small plasmids especially those from the Rep-1 superfamily are truly enigmatic, encoding only hypothetical proteins of unknown function, leading to the question of whether these small plasmids are “good” or “bad” to their host A. baumannii.

The plasmid diversity ofAcinetobacter bereziniaeHPC229 provides clues on the ability of the species to thrive on both clinical and environmental habitats

“…The presence of small cryptic plasmids lacking known replication initiatior protein genes has been already described in A. baumannii [6]. Similarly, two of the plasmids found in A. bereziniae HPC229, pAbe229-4 (4,450 bp, 36.4% GC; Fig 4A) and pAbe229-1 (1,329 bp, 36.9% GC; Fig 4B) fall into this category (S2 Table).…”

“…A. baumannii clinical strains contain a varied repertoire of plasmids [2,3,6,13,17,29]. Many of them encode only a limited number of functions generally related to mobilization, a TA system, and a replicase of the Rep_3 superfamily, and are designated as “small” plasmids [6]. As detailed below, HPC229 plasmids pAbe229-15 and pAbe229-9 fulfill these traits, and could then be included in this category.…”

“…Current plasmid typing schemes exploit the more conserved backbone modules associated with replication (Rep typing) and/or mobility (MOB typing) [3,5]. Still, a caveat of these schemes is that plasmids lacking Rep or MOB genes escape classification schemes [6]. In this context, the rapid advance of whole genome sequence methodologies (WGS), by providing complete (or near-complete) plasmid sequences, has helped to overcome in part these limitations by providing valuable insights into the evolution of the accesory regions of the plasmids present in particular bacterial groups [7].…”

“…This may represent a powerful mechanism not only to drive plasmid structural rearrangements but also host range expansions [13]. Several authors have proposed in fact that the Acinetobacter XerC/XerD recombination system may mediate the mobilization of different DNA segments carrying adaptive or stability traits, a situation that includes antimicrobial resistance, heavy metal resistance, and toxin-antitoxin (TA) genes among others [6,13,15-18].…”

Comparative analysis of intracellular and extracellular antibiotic resistance gene abundance in anaerobic membrane bioreactor effluent

“…Neisseria gonorrhea and Helicobacter pylori). While the transformation of exDNA may be 95 limited to smaller plasmids and not be effective at disseminating large multi-drug resistant 96 plasmids, smaller non-conjugative plasmids can also confer multi-drug resistance in 97 bacteria (San Millan, et al, 2009, Lean andYeo, 2017). Therefore, the direct loading of 98 exARGs, iARGs, and ARB to areas of potential human contact could significantly 99 accelerate the development of antibiotic resistant human pathogens.…”