The AbaR antibiotic resistance islands found in Acinetobacter baumannii global clone 1 – Structure, origin and evolution

Abstract

In multiply resistant Acinetobacter baumannii, complex transposons located in the chromosomal comM gene carry antibiotic and heavy metal resistance determinants. For one type, known collectively as AbaR, the ancestral form, AbaR0, entered a member of global clone 1 (GC1) in the mid 1970s and continued to evolve in situ forming many variants. In AbaR0, antibiotic and mercuric ion resistance genes are located between copies of a cadmium-zinc resistance transposon, Tn6018, and this composite transposon is in a class III transposon, Tn6019, carrying arsenate/arsenite resistance genes and five tni transposition genes. The antibiotic resistance genes in the AbaR0 and derived AbaR3 configurations are aphA1b, bla_TEM, catA1, sul1, tetA(A), and cassette-associated aacC1 and aadA1 genes. These genes are in a specific arrangement of fragments from well-known transposons, e.g. Tn1, Tn1721, Tn1696 and Tn2670, that arose in an IncM1 plasmid. All known GC1 lineage 1 isolates carry AbaR0 or AbaR3, which arose around 1990, or a variant derived from one of them. Variants arose via deletions caused by one of three internal IS26s, by recombination between duplicate copies of sul1 or Tn6018, or by gene cassette addition or replacement. A few GC2 isolates also carry an AbaR island with different cassette-associated genes, aacA4 and oxa20.

Introduction

Multiply antibiotic resistant Acinetobacter spp. have become an increasingly important cause of nosocomial infections (Clark et al., 2016; Perez et al., 2007; Towner, 2009; Wong et al., 2017) and are included in the ESKAPE group of nosocomial pathogens where antibiotic resistance is a serious problem (Boucher et al., 2009; Pendleton et al., 2013). In Europe, the increase in antimicrobial resistance was attributed to the spread of three clones of A. baumannnii, designated European clones I, II and III (Dijkshoorn et al., 1996; Hamouda et al., 2010; Nemec et al., 2008; Turton et al., 2007; van Dessel et al., 2004; Zarrilli et al., 2013). However, in the late 2000s, as typing was simplified and information about multiply antibiotic resistant A. baumannii isolates from other continents gradually became available, it became clear that the reach of isolates from two of these groups, namely I and II, was much greater as they were also found on other continents such as North America (Adams et al., 2010, 2008), Australia (Post and Hall, 2009; Post et al., 2010), South America (Grosso et al., 2011; Ramírez et al., 2013) and Asia (Fu et al., 2010; Kim et al., 2013; Lee et al., 2011; Peymani et al., 2012; Solomennyi et al., 2015; Sung et al., 2012) as well as in various other countries (Diancourt et al., 2010; Higgins et al., 2010; Mugnier et al., 2010). Consequently, in this review the terms Global Clone 1 (GC1) and Global Clone 2 (GC2) will be used to replace European Clones I and II or International Clones I and II, as this better reflects the global distribution of isolates belonging to these clonal complexes. GC1 and GC2 correspond to the clonal complexes CC1 and CC2 in the Institut Pasteur multilocus sequence typing (MLST) scheme (Diancourt et al., 2010).

Multiple resistance in Acinetobacter species and even resistance to all antibiotics available at the time was first noted in the 1970s (Perez et al., 2007; Towner, 2009). However, detailed examination of the context of acquired antibiotic resistance in A. baumannii began late relative to studies of other Gram negative pathogens. The first large antibiotic resistance gene cluster found in an A. baumannii isolate to be completely sequenced was from a multiply resistant strain, AYE, from France (Fournier et al., 2006). AYE contains an 86 kb resistance island that was designated AbaR1 (A. baumannii resistance) (Fournier et al., 2006). AbaR1 is a complex transposon that is located in the chromosome rather than in a plasmid. It is includes both antibiotic and heavy metal resistance genes and the 18 antibiotic resistance genes, some of which are present in multiple copies, confer resistance to most of the known classes of antibiotics. The AYE isolate was later shown to be sequence group SG2 (Turton et al., 2007), corresponding to European clone I or GC1.

A number of complex transposon types that carry resistance genes have been found in the same location as AbaR1 and though they include related components and are likely to have a similar movement mechanism, each type has a separate evolutionary history. In this review, we have drawn together what is known about the structure of one type, the AbaR-type genomic resistance islands that have since been found in the majority of antibiotic resistant GC1 isolates, and occasionally in GC2 isolates. How they are distinguished from other resistance island types is addressed. Then their arrangements are compared. Their origin, evolution and movement are also considered.