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Genomic comparison of multi-drug resistant invasive and colonizing Acinetobacter baumannii isolated from diverse human body sites reveals genomic plasticity.

ABSTRACT: Acinetobacter baumannii has recently emerged as a significant global pathogen, with a surprisingly rapid acquisition of antibiotic resistance and spread within hospitals and health care institutions. This study examines the genomic content of three A. baumannii strains isolated from distinct body sites. Isolates from blood, peri-anal, and wound sources were examined in an attempt to identify genetic features that could be correlated to each isolation source.Pulsed-field gel electrophoresis, multi-locus sequence typing and antibiotic resistance profiles demonstrated genotypic and phenotypic variation. Each isolate was sequenced to high-quality draft status, which allowed for comparative genomic analyses with existing A. baumannii genomes. A high resolution, whole genome alignment method detailed the phylogenetic relationships of sequenced A. baumannii and found no correlation between phylogeny and body site of isolation. This method identified genomic regions unique to both those isolates found on the surface of the skin or in wounds, termed colonization isolates, and those identified from body fluids, termed invasive isolates; these regions may play a role in the pathogenesis and spread of this important pathogen. A PCR-based screen of 74 A. baumanii isolates demonstrated that these unique genes are not exclusive to either phenotype or isolation source; however, a conserved genomic region exclusive to all sequenced A. baumannii was identified and verified.The results of the comparative genome analysis and PCR assay show that A. baumannii is a diverse and genomically variable pathogen that appears to have the potential to cause a range of human disease regardless of the isolation source.

SUBMITTER: Sahl JW

PROVIDER: S-EPMC3126785 | biostudies-literature | 2011 Jun

REPOSITORIES: biostudies-literature

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Genomic comparison of multi-drug resistant invasive and colonizing Acinetobacter baumannii isolated from diverse human body sites reveals genomic plasticity.

Sahl Jason W JW Johnson J Kristie JK Harris Anthony D AD Phillippy Adam M AM Hsiao William W WW Thom Kerri A KA Rasko David A DA

BMC genomics 20110604

<h4>Background</h4>Acinetobacter baumannii has recently emerged as a significant global pathogen, with a surprisingly rapid acquisition of antibiotic resistance and spread within hospitals and health care institutions. This study examines the genomic content of three A. baumannii strains isolated from distinct body sites. Isolates from blood, peri-anal, and wound sources were examined in an attempt to identify genetic features that could be correlated to each isolation source.<h4>Results</h4>Pul ...[more]

PMID: 21639920

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Project description:BackgroundAcinetobacter baumannii is a common nosocomial pathogen that poses a huge threat to global health. Owing to the severity of A. baumannii infections, it became necessary to investigate the epidemiological characteristics of A. baumannii in Chinese hospitals and find the reasons for the high antibiotic resistance rate and mortality. This study aimed to investigate the epidemiologic and genetic characteristics of A. baumannii isolated from patients with hospital acquired pneumonia (HAP), bloodstream infection (BSI) and urinary tract infection (UTI) in China and uncover potential mechanisms for multi-drug resistance and virulence characteristics of A. baumannii isolates.ResultsAll isolates were classified into two primary clades in core gene-based phylogenetic relationship. Clonal complex 208 (CC208) mainly consisted of ST195 (32 %) and ST208 (24.6 %). CC208 and non-CC208 isolates had carbapenem resistance rates of 96.2 and 9.1 %, respectively. Core genes were enriched in 'Amino acid transport and metabolism', 'Translation', 'Energy production and conversion', 'Transcription', 'Inorganic ion transport and metabolism' and 'Cell wall/membrane/envelope synthesis'. Most isolates possessed virulence factors related to polysaccharide biosynthesis, capsular polysaccharide synthesis and motility. Eleven isolates belong to ST369 or ST191 (oxford scheme) all had the virulence factor cap8E and it had a higher positive rate in UTI (35.3 %) than in BSI (18.9 %) and HAP (12.9 %). ABGRI1 antibiotic resistance islands were responsible for streptomycin, tetracycline and sulfonate resistance. The blaOXA-23 gene was the most probable cause for carbapenem resistance, although the blaOXA-66 gene with nonsynonymous SNPs (F82L, I129L) was not.ConclusionsA. baumannii is a genomically variable pathogen that has the potential to cause a range of infectious diseases. There is high proportion of carbapenem resistance in isolates from all three infection sites (HAP, BSI and UTI), which can be attributed to the blaOXA-23 gene. CC208 is the predominant clone in blaOXA-23-carrying A. baumannii that should be monitored. Virulence factors involving bacteria motility and polysaccharide biosynthesis which are widespread in clinical A. baumannii strains deserve our attention.

Project description:Acinetobacter baumannii has become one of the most important multidrug-resistant nosocomial pathogens all over the world. Nonetheless, very little is known about the diversity of A. baumannii lineages coexisting in hospital settings. Here, using whole-genome sequencing, epidemiological data, and antimicrobial susceptibility tests, we uncover the transmission dynamics of extensive and multidrug-resistant A. baumannii in a tertiary hospital over a decade. Our core genome phylogeny of almost 300 genomes suggests that there were several introductions of lineages from international clone 2 into the hospital. The molecular dating analysis shows that these introductions happened in 2006, 2007, and 2013. Furthermore, using the accessory genome, we show that these lineages were extensively disseminated across many wards in the hospital. Our results demonstrate that accessory genome variation can be a very powerful tool for conducting genomic epidemiology. We anticipate future studies employing the accessory genome along with the core genome as a powerful phylogenomic strategy to track bacterial transmissions over very short microevolutionary scales. IMPORTANCE Whole-genome sequencing for epidemiological investigations (genomic epidemiology) has been of paramount importance to understand the transmission dynamics of many bacterial (and nonbacterial) pathogens. Commonly, variation in the core genome, single nucleotide polymorphisms (SNPs), is employed to carry out genomic epidemiology. However, at very short periods of time, the core genome might not have accumulated enough variation (sufficient SNPs) to tell apart isolates. In this scenario, gene content variation in the accessory genome can be an option to conduct genomic epidemiology. Here, we used the accessory genome, as well as the core genome, to uncover the transmission dynamics of extensive and multidrug-resistant A. baumannii in a tertiary hospital for a decade. Our study shows that accessory genome variation can be a very powerful tool for conducting genomic epidemiology.

Project description:Acinetobacter baumannii causes severe, fulminant, community-acquired pneumonia (CAP) in tropical and subtropical regions. We compared the population structure, virulence and antimicrobial resistance determinants of northern Australian community-onset A. baumannii strains with local and global strains. We performed whole-genome sequencing on 55 clinical and five throat colonization A. baumannii isolates collected in northern Australia between 1994 and 2016. Clinical isolates included CAP (n=41), healthcare-associated pneumonia (n=7) and nosocomial bloodstream (n=7) isolates. We also included 93 publicly available international A. baumannii genome sequences in the analyses. Patients with A. baumannii CAP were almost all critically unwell; 82 % required intensive care unit admission and 18 % died during their inpatient stay. Whole-genome phylogenetic analysis demonstrated that community-onset strains were not phylogenetically distinct from nosocomial strains. Some non-multidrug-resistant local strains were closely related to multidrug-resistant strains from geographically distant locations. Pasteur sequence type (ST)10 was the dominant ST and accounted for 31/60 (52 %) northern Australian strains; the remainder belonged to a diverse range of STs. The most recent common ancestor for ST10 was estimated to have occurred in 1738 (95 % highest posterior density, 1626-1826), with evidence of multiple introduction events between Australia and Southeast Asia between then and the present day. Virulence genes associated with biofilm formation and the type 6 secretion system (T6SS) were absent in many strains, and were not associated with in-hospital mortality. All strains were susceptible to gentamicin and meropenem; none carried an AbaR resistance island. Our results suggest that international dissemination of A. baumannii is occurring in the community on a contemporary timescale. Genes associated with biofilm formation and the T6SS may not be required for survival in community niches. The relative contributions of host and bacterial factors to the clinical severity of community-onset A. baumannii infection require further investigation.

Dataset Information

Genomic comparison of multi-drug resistant invasive and colonizing Acinetobacter baumannii isolated from diverse human body sites reveals genomic plasticity.

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Genomic comparison of multi-drug resistant invasive and colonizing Acinetobacter baumannii isolated from diverse human body sites reveals genomic plasticity.

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