Large-Scale Identification of AbaR-Type Genomic Islands in Acinetobacter baumannii Reveals Diverse Insertion Sites and Clonal Lineage-Specific Antimicrobial Resistance Gene Profiles

Abstract

AbaR-type genomic islands (AbaRs) are important elements responsible for antimicrobial resistance in Acinetobacter baumannii. This study performed a large-scale identification of AbaRs to understand their distribution and compositions of antimicrobial resistance genes. We identified 2.89-kb left-end and 1.87-kb right-end conserved sequences (CSs) and developed a bioinformatics approach to identify AbaRs, using the CSs as signatures, in 3,148 publicly available genomes. AbaRs were prevalent in A. baumannii, being found in 2,091 genomes. They were sparse in other Acinetobacter species and confined only to this genus. Results from 111 complete genomes showed that over 85% of AbaRs resided on chromosomes. The external flanks adjacent to the inverted repeats available in all identified CSs were mapped to an AbaR-free chromosome or searched in the NCBI database for empty loci to define insertion sites. Surprisingly, 84 insertion sites with diverse origins were revealed, including 51 scattered on the chromosome, 20 plasmid borne, 12 located on prophages, transposons, ISAba1, complex AbaRs, and genomic islands of other types, and one uncharacterized, and some were strongly associated with clonal lineages. Finally, we found 994 antimicrobial resistance genes covering 28 unique genes from 70.9% (299/422) of intact AbaRs currently available. The resistance gene profiles displayed an apparent clonal lineage-specific pattern, highlighting the distinct features of AbaRs in global clone 1 (GC1) and GC2. The tet(B) gene was highly specific to the AbaRs in GC2. In conclusion, AbaRs have diverse insertion sites on the chromosome and mobile genetic elements (MGEs) and display distinct antimicrobial resistance gene profiles in different clonal lineages.

Comparative Genomics of Acinetobacter baumannii Clinical Strains From Brazil Reveals Polyclonal Dissemination and Selective Exchange of Mobile Genetic Elements Associated With Resistance Genes

“…The sequencing of several A. baumannii genomes revealed a wide repertoire of antimicrobial resistance genes, many of which associated with transposable elements and insertion sequences and which might be found in genomic islands (GIs), known as AbaR (Zhu et al, 2013;Liu et al, 2014;Bi et al, 2019). Several AbaR islands have been described which can vary in size and are dynamically reshaped mainly due to the activity of transposases, recombinases and integrases (Krizova et al, 2011;Li et al, 2015;Hamidian and Hall, 2018;Bi et al, 2019). Resistance genes can also be found within plasmids, which can be exchanged intra-and interspecies (Leungtongkam et al, 2018;Wibberg et al, 2018) and even by prophages (Wachino et al, 2019).…”

Targeted transposition with Tn7 elements: safe sites, mobile plasmids, CRISPR/Cas and beyond

“…The comM gene product appears to play a role in integrating horizontally acquired DNA (Nero et al , ), but any advantage that the transposon may gain by inactivating this gene remains unclear. Tn6022‐related elements also account for the AbaR‐type genomic islands that are common in pathogenic Acinetobacter baumannii (Bi et al , ), although as indicated previously, relatives of this element are found broadly across bacteria and outside of clinical settings (Peters et al , ).…”

Scarless removal of large resistance island AbaR results in antibiotic susceptibility and increased natural transformability in Acinetobacter baumannii

“…Acinetobacter baumannii is responsible for healthcare-associated infections and concerns because of its intrinsic resistance to many antimicrobials and its ability to acquire resistance genes (1,2). A potential contributor to multi-drug resistance of A. baumannii is a genomic island, named AbaR, with a great diversity in gene content and carrying multiple putative antibiotic-resistance genes (3,4). The first report of AbaR described a large genomic island of 86 kbp in the epidemic A. baumannii strain AYE in 2006 (5).…”

“…The first report of AbaR described a large genomic island of 86 kbp in the epidemic A. baumannii strain AYE in 2006 (5). Since then, analysis of more than 3000 A. baumannii genomes deposited in the NCBI database revealed that AbaR are present in nearly 65% of them (4). With a transposon backbone, AbaR islands are considered as mobile genetic elements and present a modular structure (3,(6)(7)(8).…”

“…With a transposon backbone, AbaR islands are considered as mobile genetic elements and present a modular structure (3,(6)(7)(8). Although AbaR may contain up to 25 putative antibiotic-resistance genes, most AbaR carry three to four genes conferring resistance mainly to aminoglycosides and tetracycline and with a median length of 20 kbp (4,9). Despite increasing genomic data, the actual contribution of AbaR-type islands to antibiotic resistance, host infection or bacterial fitness has not been fully evaluated.…”