The origin of Acinetobacter baumannii TYTH-1: a comparative genomics study

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Abstract

There have been increasing reports of blaOXA-23-carrying strains of carbapenem-resistant Acinetobacter baumannii (CRAB), which has become a significant public health concern in Taiwan. To determine the origin of these CRAB strains, the prevalence of CRAB and blaOXA-23-carrying CRAB in a regional hospital was analysed retrospectively. The genome of A. baumannii TYTH-1 was completely sequenced and annotated. Multiple comparative genomics studies, including phylogenetic analysis, functional comparison via the Clusters of Orthologous Groups (COGs) database, and determination of variance in GC profiles in the whole genome and gene arrangements in resistance islands, were performed using 11 completely sequenced A. baumannii genomes. blaOXA-23-carrying CRAB isolates became dominant clones in 2007. A comparative genomics analysis revealed a common strain lineage between Taiwanese strains (TYTH-1 and TCDC-AB0715) and Chinese strains (MDR-TJ and MDR-ZJ06). Phylogenetic studies and GC profiles showed that the genome of TYTH-1 was closest to MDR-ZJ06. However, the resistance island of TYTH-1 (RITYTH-1) was nearly identical to that of RIMDT-TJ. The functional category for COGs was similar in the tested genomes. The results reveal that dissemination of blaOXA-23-carrying CRAB in Taiwan may have been mediated by the transfer of people between Taiwan and China during 2007. The global spread of CRAB is now a worldwide public health problem. In Taiwan, the government needs to focus more attention on the importance of identifying and tracing resistant pathogens and issuing notifications of CRAB infections.

Introduction

In the last two decades, Acinetobacter baumannii has gradually emerged worldwide as a nosocomial pathogen. Common infections include ventilator-associated pneumonia, bacteraemia, burn wound infections and urinary tract infections [1]. Acinetobacter infections may pose difficulties because nosocomial isolates are typically resistant to a wide variety of antimicrobial agents. Carbapenems, primarily imipenem and meropenem, have been used to treat multidrug-resistant A. baumannii (MDR-AB) infections [1]. However, there are increasing reports of carbapenem resistance in A. baumannii. To date, one of the most important ways that the spread of multidrug resistance in the hospital environment is enhanced is via the horizontal transfer of antibiotic resistance genes within a shared gene pool [2]. Several reports have shown that large antibiotic resistance islands (AbaRs) mediated by horizontal gene transfer were found in the genomes of epidemic A. baumannii strains [3]. In addition, these AbaRs in A. baumannii strains of the same lineage shared the same origin [4]. These results imply that AbaRs may play important roles in the resistance of A. baumannii strains and may serve as evolutionary candidates.

Recently, the rapid increase in MDR-AB, particularly carbapenem-resistant A. baumannii (CRAB), has become a significant public health concern [1]. Several class D β-lactamases [carbapenem-hydrolysing class D β-lactamases (CHDLs)], including OXA-23, OXA-24, OXA-58 and intrinsic OXA-51-like enzymes, are known to be important contributors to carbapenem resistance [5]. Among the OXA-type carbapenemases, OXA-23 is now a candidate gene in CRAB isolated from several countries [6].

A previous report from China showed that clonal spread of blaOXA-23-carrying imipenem-resistant A. baumannii (IRAB) isolates was identified in 16 cities in China in 2005 [7]. In our previous study, which was conducted in a regional hospital in Taiwan, the emergence and spread of blaOXA-23-carrying IRAB in Taiwan occurred from 2006 to 2007 [8]. In addition, the appearance of blaOXA-23-carrying IRAB was reported in several hospitals in Taiwan in 2007 [9]. To date, three complete A. baumannii genome sequences [MDR-ZJ06 (Zhejiang, China), TCDC-AB0715 (Taiwan) and MDR-TJ (Tianjin, China)] were released between 2011 and 2012 [10], [11], [12]. Notably, MDR-ZJ06 was one of the major clones disseminated in several cities in China [7] and the strain was isolated in 2006. Based on phylogenetic analysis of all completed A. baumannii genomes, these three genomes are closely related [10] and all three strains possess blaOXA-23 and blaOXA-66 genes.

In this study, to determine the genetic basis of IRAB strains and the genetic lineages of Taiwan clones and two other clones isolated in China, TYTH-1 was completely sequenced and comparative analyses were performed.

Section snippets

Hospital setting and bacterial isolates

The Hsin-Chu branch of National Taiwan University Hospital (NTUH) is a regional teaching hospital with 699 ward beds in northern Taiwan. All clinical imipenem-resistant Acinetobacter spp. isolates collected between January 2005 and December 2008 were stored at −80 °C in trypticase soy broth (Difco Laboratories, Detroit, MI) supplemented with 20% glycerol before testing. Isolates were transported to the clinical microbiology laboratory of Yuanpei University (Hsin-Chu City, Taiwan) for further

Trends for carbapenem-resistant Acinetobacter baumannii (CRAB) and blaOXA-23-carrying CRAB

The rapidly increasing incidence of CRAB (5% in 2005 to 51% in 2008) and blaOXA-23-carrying CRAB (0% in 2005 to 47% in 2008) is shown in Fig. 1A. Monthly surveillance studies between 2007 and 2008 showed that this trend started in August 2007 (Fig. 1B). In addition, PFGE typing demonstrated that an outbreak occurred between April 2007 and April 2008. Of the patients with clonally related isolates, none of them were abroad 2 months before their admission to the NTUH Hsin-Chu Branch.

Susceptibility profiles

The minimum

Discussion

The emergence and spread of blaOXA-23,-24/40,-58 CRAB in Asia-Pacific nations was identified between 2006 and 2007 [6]. Notably, the first report regarding the outbreak of blaOXA-23-carrying CRAB in a Chinese hospital was recorded in 2003 [26]. Furthermore, the wide spread of outbreak strains occurred in 16 cities in China in 2005 [7]. In Taiwan, the first report noting the occurrence of blaOXA-23-carrying CRAB was documented at the NTUH Hsin-Chu Branch in 2006 [8]. According to this report, no

Acknowledgments

The authors thank the members of the Department of Laboratory, National Taiwan University Hospital Hsin-Chu Branch (Hsin-Chu City, Taiwan) for providing clinical isolates of Acinetobacter baumannii.

Funding: The present work was supported by a grant from the National Science Council (grant NSC 100-2221-E-126 -010–MY3).

Competing interest: None declared.

Ethical approval: Not required.

References (30)

  • M.F. Lin et al.

    Emergence and dissemination of blaOXA-23-carrying imipenem-resistant Acinetobacter sp. in a regional hospital in Taiwan

    J Microbiol Immunol Infect

    (2011)
  • F. Perez et al.

    Global challenge of multidrug-resistant Acinetobacter baumannii

    Antimicrob Agents Chemother

    (2007)
  • J.K. Valenzuela et al.

    Horizontal gene transfer in a polyclonal outbreak of carbapenem-resistant Acinetobacter baumannii

    J Clin Microbiol

    (2007)
  • V. Post et al.

    Evolution of AbaR-type genomic resistance islands in multiply antibiotic-resistant Acinetobacter baumannii

    J Antimicrob Chemother

    (2010)
  • L. Krizova et al.

    Diversity and evolution of AbaR genomic resistance islands in Acinetobacter baumannii strains of European clone I

    Antimicrob Agents Chemother

    (2011)
  • J. Walther-Rasmussen et al.

    OXA-type carbapenemases

    J Antimicrob Chemother

    (2006)
  • R.E. Mendes et al.

    Emergence and widespread dissemination of OXA-23, -24/40 and -58 carbapenemases among Acinetobacter spp. in Asia-Pacific nations: report from the SENTRY Surveillance Program

    J Antimicrob Chemother

    (2009)
  • H. Zhou et al.

    Clonal spread of imipenem-resistant Acinetobacter baumannii among different cities of China

    J Clin Microbiol

    (2007)
  • M.H. Lee et al.

    Dissemination of multidrug-resistant Acinetobacter baumannii carrying blaOXA-23 from hospitals in central Taiwan

    J Microbiol Immunol Infect

    (2012)
  • H. Huang et al.

    Complete genome sequence of Acinetobacter baumannii MDR-TJ and insights into its mechanism of antibiotic resistance

    J Antimicrob Chemother

    (2012)
  • H. Zhou et al.

    Genomic analysis of the multidrug-resistant Acinetobacter baumannii strain MDR-ZJ06 widely spread in China

    Antimicrob Agents Chemother

    (2011)
  • C.C. Chen et al.

    Genome sequence of a dominant, multidrug-resistant Acinetobacter baumannii strain, TCDC-AB0715

    J Bacteriol

    (2011)
  • S.G. Bartual et al.

    Development of a multilocus sequence typing scheme for characterization of clinical isolates of Acinetobacter baumannii

    J Clin Microbiol

    (2005)
  • R. Li et al.

    SOAP2: an improved ultrafast tool for short read alignment

    Bioinformatics

    (2009)
  • S.K. Shukla et al.

    Optical mapping reveals a large genetic inversion between two methicillin-resistant Staphylococcus aureus strains

    J Bacteriol

    (2009)
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