Abstract
Acinetobacter baumannii is an opportunistic bacterial pathogen infecting immunocompromised patients and has gained attention worldwide due to its increased antimicrobial resistance. Here, we report a comparative whole-genome sequencing and analysis coupled with an assessment of antibiotic resistance of 46 Acinetobacter strains (45 A. baumannii plus one Acinetobacter nosocomialis) originated from five hospitals from the city of Recife, Brazil, between 2010 and 2014. An average of 3,809 genes were identified per genome, although only 2,006 genes were single copy orthologs or core genes conserved across all sequenced strains, with an average of 42 new genes found per strain. We evaluated genetic distance through a phylogenetic analysis and MLST as well as the presence of antibiotic resistance genes, virulence markers and mobile genetic elements (MGE). The phylogenetic analysis recovered distinct monophyletic A. baumannii groups corresponding to five known (ST1, ST15, ST25, ST79, and ST113) and one novel ST (ST881, related to ST1). A large number of ST specific genes were found, with the ST79 strains having the largest number of genes in common that were missing from the other STs. Multiple genes associated with resistance to β-lactams, aminoglycosides and other antibiotics were found. Some of those were clearly mapped to defined MGEs and an analysis of those revealed known elements as well as a novel Tn7-Tn3 transposon with a clear ST specific distribution. An association of selected resistance/virulence markers with specific STs was indeed observed, as well as the recent spread of the OXA-253 carbapenemase encoding gene. Virulence genes associated with the synthesis of the capsular antigens were noticeably more variable in the ST113 and ST79 strains. Indeed, several resistance and virulence genes were common to the ST79 and ST113 strains only, despite a greater genetic distance between them, suggesting common means of genetic exchange. Our comparative analysis reveals the spread of multiple STs and the genomic plasticity of A. baumannii from different hospitals in a single metropolitan area. It also highlights differences in the spread of resistance markers and other MGEs between the investigated STs, impacting on the monitoring and treatment of Acinetobacter in the ongoing and future outbreaks.
Highlights
Acinetobacter baumannii is an opportunistic Gram-negative bacterium considered one of the most prevalent pathogens associated to nosocomial infections, especially among immunocompromised patients
In order to investigate Acinetobacter clinical strains associated with hospital acquired human infection in Northeastern Brazil, we selected 46 Acinetobacter strains from patients hospitalized in five hospitals from Recife
Prior to any genetic analysis, we opted to determine the antimicrobial susceptibility profile exhibited by the 46 Acinetobacter clinical strains against eleven different antimicrobial agents using the Clinical and Laboratory Standards Institute (CLSI) broth microdilution method
Summary
Acinetobacter baumannii is an opportunistic Gram-negative bacterium considered one of the most prevalent pathogens associated to nosocomial infections, especially among immunocompromised patients. The genus Acinetobacter has gained attention due to the increasing number of reported multi-drug resistant (MDR) clinical strains. These represent a great challenge in terms of treatment of infections and the elimination of pathogenic Acinetobacter species. Acinetobacter baumannii exhibits intrinsic resistance to many classes of antimicrobial agents and is further capable of developing resistance to virtually all other classes of agents used in the clinical practices to treat Gram-negative infections (Esterly et al, 2011; Leclercq et al, 2013; Nowak and Paluchowska, 2016; Lee et al, 2017). In MDR strains more than one of these mechanisms can work synergically (Sen and Joshi, 2016)
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