A GC1 Acinetobacter baumannii isolate carrying AbaR3 and the aminoglycoside resistance transposon TnaphA6 in a conjugative plasmid

Hamidian, Mohammad; Holt, Kathryn E.; Pickard, Derek; Dougan, Gordon; Hall, Ruth M.

doi:10.1093/jac/dkt454

Cited by 70 publications

(76 citation statements)

References 22 publications

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“…2). In A. baumannii clinical isolates, the same features are present in the chromosomal regions flanking the Tn125 and TnaphA6 composite transposons, the most recently identified being composed of the aphA6 aminoglycoside resistance gene surrounded by two ISAba125 elements (8,21). The preference for AT-rich regions, previously observed for ISAba1 (22), is consistent with the Acinetobacter species origin of ISAba125, whose genome is AT rich (58 to 62%).…”

Section: Discussionsupporting

confidence: 72%

Transposition of Tn 125 Encoding the NDM-1 Carbapenemase in Acinetobacter baumannii

Bontron

Nordmann

Poirel

2016

Antimicrob Agents Chemother

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The bla NDM-1 gene encodes a carbapenemase that confers resistance to almost all ␤-lactams, including last-resort carbapenems. This is increasingly reported worldwide in nosocomial and community-acquired Gram-negative bacteria. Acinetobacter baumannii is an important opportunistic pathogen that is considered an intermediate reservoir for the bla NDM-1 gene. In this species, the bla NDM-1 gene is located within the Tn125 composite transposon. The mechanism driving the mobility of Tn125 has not yet been elucidated. Here we experimentally demonstrated the transposition of Tn125 in A. baumannii. Systematic 3-bp duplication of the target site, being the signature of transposition, was evidenced. The target site consensus sequence for Tn125 transposition was found to be GC enriched at the duplicated 3 bp and AT rich in the vicinity. Transposition frequency was not influenced by temperature changes or by exposure to subinhibitory concentrations of various antibiotics. This work is the first direct evidence of the functionality of a composite transposon in A. baumannii. It provides a mechanistic clue for the dissemination of the bla NDM-1 gene in Acinetobacter spp. and subsequently among Enterobacteriaceae.

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Section: Discussionsupporting

confidence: 72%

Transposition of Tn 125 Encoding the NDM-1 Carbapenemase in Acinetobacter baumannii

Bontron

Nordmann

Poirel

2016

Antimicrob Agents Chemother

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“…The replication initiation gene corresponds to a previously undefined plasmid replication group (57). The other two plasmids are closely related to previously described plasmids (8,58), the larger of which was shown to be transmissible by conjugation (58). Strain AB5075 is closely related to three other strains of the GC1 group (AB0057, AYE, and 307-0294), which are diverse in origin and which represent both MDR and drug-susceptible phenotypes (see Fig.…”

Section: Resultsmentioning

confidence: 68%

“…1; also see Text S1 in the supplemental material). The plasmid resistance island represents a novel insertion in a known plasmid (58) and exhibits the remarkable feature that it is flanked by direct repeats of a 439-bp miniature inverted-repeat transposable element (MITE)-like sequence (61-64) ( Fig. 1; see Text S1 in the supplemental material).…”

Section: Resultsmentioning

confidence: 99%

“…1; see Text S1 in the supplemental material). The insertion site shows a 5-bp duplication, suggesting that the entire island was inserted into the plasmid by transposition (58,62,64). The island has a complex class 1 integron structure seen in one other A. baumannii strain (65) and carries genes for resistance to ␤-lactams (the extended-spectrum ␤-lactamase GES-14), aminoglycosides, chloramphenicol, and trimethoprim (see Text S1 in the supplemental material).…”

Section: Resultsmentioning

confidence: 99%

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Resources for Genetic and Genomic Analysis of Emerging Pathogen Acinetobacter baumannii

et al. 2015

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Acinetobacter baumannii is a Gram-negative bacterial pathogen notorious for causing serious nosocomial infections that resist antibiotic therapy. Research to identify factors responsible for the pathogen's success has been limited by the resources available for genome-scale experimental studies. This report describes the development of several such resources for A. baumannii strain AB5075, a recently characterized wound isolate that is multidrug resistant and displays robust virulence in animal models. We report the completion and annotation of the genome sequence, the construction of a comprehensive ordered transposon mutant library, the extension of high-coverage transposon mutant pool sequencing (Tn-seq) to the strain, and the identification of the genes essential for growth on nutrient-rich agar. These resources should facilitate large-scale genetic analysis of virulence, resistance, and other clinically relevant traits that make A. baumannii a formidable public health threat. IMPORTANCEAcinetobacter baumannii is one of six bacterial pathogens primarily responsible for antibiotic-resistant infections that have become the scourge of health care facilities worldwide. Eliminating such infections requires a deeper understanding of the factors that enable the pathogen to persist in hospital environments, establish infections, and resist antibiotics. We present a set of resources that should accelerate genome-scale genetic characterization of these traits for a reference isolate of A. baumannii that is highly virulent and representative of current outbreak strains.A cinetobacter baumannii is a Gram-negative opportunistic pathogen that causes infections with serious morbidity and mortality and is one of a group of six pathogens responsible for most multidrug-resistant (MDR) nosocomial infections (the ESKAPE pathogens, i.e., Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) (1, 2). The pathogen is infamous for its ability to persist in hospital settings, a feature that reflects its capacity for long-term survival on abiotic surfaces through resistance to desiccation and disinfectants (3).Genomic and molecular epidemiological studies of A. baumannii isolates have helped define the pathogen's global population structure, its antibiotic resistance gene repertoire, the size and content of its pangenome, and phylogenetic relationships among outbreak strains (3-6). Three primary clonal lineages (GC1 to GC3) appear responsible for the majority of hospital outbreaks globally (7). Although these lineages display restricted genetic diversity among core genes (7), the species' genome is actually quite dynamic. Strains display striking variability in accessory gene content (5, 8), including antibiotic resistance genes (9), even among related isolates of a single outbreak (10). This genomic variability presumably reflects the actions of transmissible plasmids, insertion elements, phage, integrons, natural transformation, and reco...

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“…Transposon-mediated passage of resistance mechanisms are well described, including those for AmpC cephalosporinases, OXA carbapenemases, KPC serine carbapenemases, and NDM or VIM metallo-carbapenemases, and aminoglycosides (101,135,136,147,148,150,155,158,159,(172)(173)(174)(175)(176)(177)(178). Indeed, transposon-mediated resistance to classically described antibiotic classes, including ␤-lactams, tetracyclines, aminoglycosides, and sulfonamides, had occurred in a global lineage of A. baumannii by the late 1970s; new resistance was subsequently acquired in transposon lineages in the 1980s as new antibiotics became available (136).…”

Section: Antibiotic Resistance Drives Outcomesmentioning

confidence: 99%

Clinical and Pathophysiological Overview of Acinetobacter Infections: a Century of Challenges

et al. 2017

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SUMMARY Acinetobacter is a complex genus, and historically, there has been confusion about the existence of multiple species. The species commonly cause nosocomial infections, predominantly aspiration pneumonia and catheter-associated bacteremia, but can also cause soft tissue and urinary tract infections. Community-acquired infections by Acinetobacter spp. are increasingly reported. Transmission of Acinetobacter and subsequent disease is facilitated by the organism's environmental tenacity, resistance to desiccation, and evasion of host immunity. The virulence properties demonstrated by Acinetobacter spp. primarily stem from evasion of rapid clearance by the innate immune system, effectively enabling high bacterial density that triggers lipopolysaccharide (LPS)–Toll-like receptor 4 (TLR4)-mediated sepsis. Capsular polysaccharide is a critical virulence factor that enables immune evasion, while LPS triggers septic shock. However, the primary driver of clinical outcome is antibiotic resistance. Administration of initially effective therapy is key to improving survival, reducing 30-day mortality threefold. Regrettably, due to the high frequency of this organism having an extreme drug resistance (XDR) phenotype, early initiation of effective therapy is a major clinical challenge. Given its high rate of antibiotic resistance and abysmal outcomes (up to 70% mortality rate from infections caused by XDR strains in some case series), new preventative and therapeutic options for Acinetobacter spp. are desperately needed.

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A GC1 Acinetobacter baumannii isolate carrying AbaR3 and the aminoglycoside resistance transposon TnaphA6 in a conjugative plasmid

Cited by 70 publications

References 22 publications

Transposition of Tn 125 Encoding the NDM-1 Carbapenemase in Acinetobacter baumannii

Transposition of Tn 125 Encoding the NDM-1 Carbapenemase in Acinetobacter baumannii

Resources for Genetic and Genomic Analysis of Emerging Pathogen Acinetobacter baumannii

Clinical and Pathophysiological Overview of Acinetobacter Infections: a Century of Challenges

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