title: Single-molecule sequencing reveals the molecular basis of multidrug-resistance in ST772 methicillin-resistant Staphylococcus aureus.
abstract: BACKGROUND
  Methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of hospital-associated infection, but there is growing awareness of the emergence of multidrug-resistant lineages in community settings around the world. One such lineage is ST772-MRSA-V, which has disseminated globally and is increasingly prevalent in India. Here, we present the complete genome sequence of DAR4145, a strain of the ST772-MRSA-V lineage from India, and investigate its genomic characteristics in regards to antibiotic resistance and virulence factors.
  
  
  RESULTS
  Sequencing using single-molecule real-time technology resulted in the assembly of a single continuous chromosomal sequence, which was error-corrected, annotated and compared to nine draft genome assemblies of ST772-MRSA-V from Australia, Malaysia and India. We discovered numerous and redundant resistance genes associated with mobile genetic elements (MGEs) and known core genome mutations that explain the highly antibiotic resistant phenotype of DAR4145. Staphylococcal toxins and superantigens, including the leukotoxin Panton-Valentinin Leukocidin, were predominantly associated with genomic islands and the phage φ-IND772PVL. Some of these mobile resistance and virulence factors were variably present in other strains of the ST772-MRSA-V lineage.
  
  
  CONCLUSIONS
  The genomic characteristics presented here emphasize the contribution of MGEs to the emergence of multidrug-resistant and highly virulent strains of community-associated MRSA. Antibiotic resistance was further augmented by chromosomal mutations and redundancy of resistance genes. The complete genome of DAR4145 provides a valuable resource for future investigations into the global dissemination and phylogeography of ST772-MRSA-V.
authors.affiliation: Menzies School of Health Research, Darwin, Northern Territory, Australia. eike.steinig@menzies.edu.au.
authors.forename: Eike J
authors.initials: EJ
authors.lastname: Steinig
authors.affiliation: Menzies School of Health Research, Darwin, Northern Territory, Australia. patiyan.andersson@menzies.edu.au.
authors.forename: Patiyan
authors.initials: P
authors.lastname: Andersson
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK. sh16@sanger.ac.uk.
authors.forename: Simon R
authors.initials: SR
authors.lastname: Harris
authors.affiliation: Menzies School of Health Research, Darwin, Northern Territory, Australia. derek.sarovich@menzies.edu.au.
authors.forename: Derek S
authors.initials: DS
authors.lastname: Sarovich
authors.affiliation: Pushpagiri Research Center, Pushpagiri Institute of Medical Sciences and Research Center, Thiruvalla, India. anandmanoharan@pushapagiri.in.
authors.forename: Anand
authors.initials: A
authors.lastname: Manoharan
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK. pc10@sanger.ac.uk.
authors.forename: Paul
authors.initials: P
authors.lastname: Coupland
authors.affiliation: School of Medicine, University of St. Andrews, St. Andrews, UK. mtgh@st-andrews.ac.uk.
authors.forename: Matthew T G
authors.initials: MT
authors.lastname: Holden
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK. parkhill@sanger.ac.uk.
authors.forename: Julian
authors.initials: J
authors.lastname: Parkhill
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK. stephen.bentley@sanger.ac.uk.
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Bentley
authors.affiliation: Department of Microbiology, University of Mississippi Medical Center, Jackson, MS, USA. darobinson@umc.edu.
authors.forename: D Ashley
authors.initials: DA
authors.lastname: Robinson
authors.affiliation: Menzies School of Health Research, Darwin, Northern Territory, Australia. steven.tong@menzies.edu.au.
authors.forename: Steven Y C
authors.initials: SY
authors.lastname: Tong
mesh_terms: D001427:Bacterial Toxins / Q000235:genetics; D001483:Base Sequence; D004269:DNA, Bacterial / Q000032:analysis*; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics*; D004768:Enterotoxins / Q000235:genetics; D005098:Exotoxins / Q000235:genetics; D016680:Genome, Bacterial; D044404:Genomic Islands; D007956:Leukocidins / Q000235:genetics; D055624:Methicillin-Resistant Staphylococcus aureus / Q000235:genetics*; D008969:Molecular Sequence Data; D017422:Sequence Analysis, DNA; D037521:Virulence Factors / Q000235:genetics
chemical_list: D001427:Bacterial Toxins; D004269:DNA, Bacterial; D004768:Enterotoxins; D005098:Exotoxins; D007956:Leukocidins; C078284:Panton-Valentine leukocidin; D037521:Virulence Factors