title: Complete genome sequence, lifestyle, and multi-drug resistance of the human pathogen Corynebacterium resistens DSM 45100 isolated from blood samples of a leukemia patient.
abstract: BACKGROUND
  Corynebacterium resistens was initially recovered from human infections and recognized as a new coryneform species that is highly resistant to antimicrobial agents. Bacteremia associated with this organism in immunocompromised patients was rapidly fatal as standard minocycline therapies failed. C. resistens DSM 45100 was isolated from a blood culture of samples taken from a patient with acute myelocytic leukemia. The complete genome sequence of C. resistens DSM 45100 was determined by pyrosequencing to identify genes contributing to multi-drug resistance, virulence, and the lipophilic lifestyle of this newly described human pathogen.
  
  
  RESULTS
  The genome of C. resistens DSM 45100 consists of a circular chromosome of 2,601,311 bp in size and the 28,312-bp plasmid pJA144188. Metabolic analysis showed that the genome of C. resistens DSM 45100 lacks genes for typical sugar uptake systems, anaplerotic functions, and a fatty acid synthase, explaining the strict lipophilic lifestyle of this species. The genome encodes a broad spectrum of enzymes ensuring the availability of exogenous fatty acids for growth, including predicted virulence factors that probably contribute to fatty acid metabolism by damaging host tissue. C. resistens DSM 45100 is able to use external L-histidine as a combined carbon and nitrogen source, presumably as a result of adaptation to the hitherto unknown habitat on the human skin. Plasmid pJA144188 harbors several genes contributing to antibiotic resistance of C. resistens DSM 45100, including a tetracycline resistance region of the Tet W type known from Lactobacillus reuteri and Streptococcus suis. The tet(W) gene of pJA144188 was cloned in Corynebacterium glutamicum and was shown to confer high levels of resistance to tetracycline, doxycycline, and minocycline in vitro.
  
  
  CONCLUSIONS
  The detected gene repertoire of C. resistens DSM 45100 provides insights into the lipophilic lifestyle and virulence functions of this newly recognized pathogen. Plasmid pJA144188 revealed a modular architecture of gene regions that contribute to the multi-drug resistance of C. resistens DSM 45100. The tet(W) gene encoding a ribosomal protection protein is reported here for the first time in corynebacteria. Cloning of the tet(W) gene mediated resistance to second generation tetracyclines in C. glutamicum, indicating that it might be responsible for the failure of minocycline therapies in patients with C. resistens bacteremia.
authors.affiliation: Institut für Genomforschung und Systembiologie, Centrum für Biotechnologie, Universität Bielefeld, Germany.
authors.forename: Jasmin
authors.initials: J
authors.lastname: Schröder
authors.forename: Irena
authors.initials: I
authors.lastname: Maus
authors.forename: Katja
authors.initials: K
authors.lastname: Meyer
authors.forename: Stephanie
authors.initials: S
authors.lastname: Wördemann
authors.forename: Jochen
authors.initials: J
authors.lastname: Blom
authors.forename: Sebastian
authors.initials: S
authors.lastname: Jaenicke
authors.forename: Jessica
authors.initials: J
authors.lastname: Schneider
authors.forename: Eva
authors.initials: E
authors.lastname: Trost
authors.forename: Andreas
authors.initials: A
authors.lastname: Tauch
mesh_terms: D000596:Amino Acids / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics; D002876:Chromosomes, Bacterial; D003352:Corynebacterium / Q000187:drug effects* / Q000235:genetics* / Q000378:metabolism; D018432:Drug Resistance, Multiple / Q000235:genetics*; D023061:Gene Order; D016680:Genome, Bacterial; D006639:Histidine / Q000378:metabolism; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000382:microbiology; D053858:Metabolic Networks and Pathways; D008826:Microbial Sensitivity Tests; D058977:Molecular Sequence Annotation; D008969:Molecular Sequence Data; D046915:Penicillin-Binding Proteins / Q000235:genetics; D010957:Plasmids / Q000235:genetics; D017422:Sequence Analysis, DNA; D037521:Virulence Factors / Q000235:genetics
chemical_list: D000596:Amino Acids; D001426:Bacterial Proteins; D046915:Penicillin-Binding Proteins; D037521:Virulence Factors; D006639:Histidine