title: Beyond the chromosome: the prevalence of unique extra-chromosomal bacteriophages with integrated virulence genes in pathogenic Staphylococcus aureus.
abstract: In Staphylococcus aureus, the disease impact of chromosomally integrated prophages on virulence is well described. However, the existence of extra-chromosomal prophages, both plasmidial and episomal, remains obscure. Despite the recent explosion in bacterial and bacteriophage genomic sequencing, studies have failed to specifically focus on extra-chromosomal elements. We selectively enriched and sequenced extra-chromosomal DNA from S. aureus isolates using Roche-454 technology and uncovered evidence for the widespread distribution of multiple extra-chromosomal prophages (ExPΦs) throughout both antibiotic-sensitive and -resistant strains. We completely sequenced one such element comprised of a 43.8 kbp, circular ExPΦ (designated ФBU01) from a vancomycin-intermediate S. aureus (VISA) strain. Assembly and annotation of ФBU01 revealed a number of putative virulence determinants encoded within a bacteriophage immune evasion cluster (IEC). Our identification of several potential ExPΦs and mobile genetic elements (MGEs) also revealed numerous putative virulence factors and antibiotic resistance genes. We describe here a previously unidentified level of genetic diversity of stealth extra-chromosomal elements in S. aureus, including phages with a larger presence outside the chromosome that likely play a prominent role in pathogenesis and strain diversity driven by horizontal gene transfer (HGT).
authors: Laboratory of Bacterial Pathogenesis and Immunology, The Rockefeller University, New York, New York, United States of America.
authors: Bryan
authors: B
authors: Utter
authors: Laboratory of Bacterial Pathogenesis and Immunology, The Rockefeller University, New York, New York, United States of America.
authors: Douglas R
authors: DR
authors: Deutsch
authors: Laboratory of Bacterial Pathogenesis and Immunology, The Rockefeller University, New York, New York, United States of America.
authors: Raymond
authors: R
authors: Schuch
authors: Laboratory of Bacterial Pathogenesis and Immunology, The Rockefeller University, New York, New York, United States of America.
authors: Benjamin Y
authors: BY
authors: Winer
authors: Henry M. Jackson Foundation, Bethesda, Maryland, United States of America; Naval Medical Research Center-Frederick, Fort Detrick, Maryland, United States of America.
authors: Kathleen
authors: K
authors: Verratti
authors: Henry M. Jackson Foundation, Bethesda, Maryland, United States of America; Naval Medical Research Center-Frederick, Fort Detrick, Maryland, United States of America.
authors: Kim
authors: K
authors: Bishop-Lilly
authors: Henry M. Jackson Foundation, Bethesda, Maryland, United States of America; Naval Medical Research Center-Frederick, Fort Detrick, Maryland, United States of America.
authors: Shanmuga
authors: S
authors: Sozhamannan
authors: Laboratory of Bacterial Pathogenesis and Immunology, The Rockefeller University, New York, New York, United States of America.
authors: Vincent A
authors: VA
authors: Fischetti
mesh_terms: D001435:Bacteriophages / Q000235:genetics / Q000502:physiology*; D002876:Chromosomes, Bacterial / Q000235:genetics* / Q000821:virology; D004279:DNA, Viral / Q000235:genetics; D014644:Genetic Variation; D016679:Genome, Viral / Q000235:genetics; D017422:Sequence Analysis, DNA; D013211:Staphylococcus aureus / Q000166:cytology / Q000235:genetics / Q000472:pathogenicity* / Q000821:virology*; D014774:Virulence / Q000235:genetics
chemical_list: D004279:DNA, Viral