Carbapenemases: Transforming Acinetobacter baumannii into a Yet More Dangerous Menace

Abstract

Acinetobacter baumannii is a common cause of serious nosocomial infections. Although community-acquired infections are observed, the vast majority occur in people with preexisting comorbidities. A. baumannii emerged as a problematic pathogen in the 1980s when an increase in virulence, difficulty in treatment due to drug resistance, and opportunities for infection turned it into one of the most important threats to human health. Some of the clinical manifestations of A. baumannii nosocomial infection are pneumonia; bloodstream infections; lower respiratory tract, urinary tract, and wound infections; burn infections; skin and soft tissue infections (including necrotizing fasciitis); meningitis; osteomyelitis; and endocarditis. A. baumannii has an extraordinary genetic plasticity that results in a high capacity to acquire antimicrobial resistance traits. In particular, acquisition of resistance to carbapenems, which are among the antimicrobials of last resort for treatment of multidrug infections, is increasing among A. baumannii strains compounding the problem of nosocomial infections caused by this pathogen. It is not uncommon to find multidrug-resistant (MDR, resistance to at least three classes of antimicrobials), extensively drug-resistant (XDR, MDR plus resistance to carbapenems), and pan-drug-resistant (PDR, XDR plus resistance to polymyxins) nosocomial isolates that are hard to treat with the currently available drugs. In this article we review the acquired resistance to carbapenems by A. baumannii. We describe the enzymes within the OXA, NDM, VIM, IMP, and KPC groups of carbapenemases and the coding genes found in A. baumannii clinical isolates.

Keywords: Acinetobacter; ESKAPE; antibiotic resistance; plasmid; β-lactam; β-lactamase.

Figure 1

Structure of carbapenems. Generic chemical structure of carbapenems. The R1 and R2 groups for imipenem and meropenem, the most used in the clinics, are shown.

Figure 2

Genetic structures of bla_OXA-23-containing elements. The structure of Tn2007, which has not been proven to transpose, is shown on top. Tn2008 and Tn2008B differ in the number of nucleotides (27 and 34, respectively) that separate bla_OXA-23 from ISAba1. Tn2006, the only structure experimentally shown to transpose [178], includes copies of ISAba1 in opposite orientations, while Tn2009 carries these insertion sequences in the same orientation. These two transposons are the only ones with the typical composite transposon structure. An extensive and detailed description of these elements was recently published [177]. ATPase*, gene coding for a putative ATPase truncated at the N-terminus. DADE, gene coding for a putative DEAD box family helicase [181]. Figure interpreted from Nigro and Hall (2016) [177].

Figure 3

Genetic map of A. baumannii transposon Tn125. Figure interpreted from Poirel et al. [257].

Figure 4

Comparison of the In42 variable region and a Tn1331 resistance genes fragment. The genetic maps of the variable region of In42 and a resistance genes fragment of Tn1331 are aligned. All attC loci are shown equally in the figure, but they are not identical at the nucleotide sequence level. The attI1* structure and functionality have been described [306]. The aac(6′)-Ib genes code for proteins that show differences at the N-termini, a known characteristic of this gene [141,309,310].