title: Evolution of hypervirulence by a MRSA clone through acquisition of a transposable element.
abstract: Staphylococcus aureus has evolved as a pathogen that causes a range of diseases in humans. There are two dominant modes of evolution thought to explain most of the virulence differences between strains. First, virulence genes may be acquired from other organisms. Second, mutations may cause changes in the regulation and expression of genes. Here we describe an evolutionary event in which transposition of an IS element has a direct impact on virulence gene regulation resulting in hypervirulence. Whole-genome analysis of a methicillin-resistant S. aureus (MRSA) strain USA500 revealed acquisition of a transposable element (IS256) that is absent from close relatives of this strain. Of the multiple copies of IS256 found in the USA500 genome, one was inserted in the promoter sequence of repressor of toxins (Rot), a master transcriptional regulator responsible for the expression of virulence factors in S. aureus. We show that insertion into the rot promoter by IS256 results in the derepression of cytotoxin expression and increased virulence. Taken together, this work provides new insight into evolutionary strategies by which S. aureus is able to modify its virulence properties and demonstrates a novel mechanism by which horizontal gene transfer directly impacts virulence through altering toxin regulation.
authors: Department of Microbiology, New York University School of Medicine, New York, NY, USA; Division of Infectious Diseases, Boston Children's Hospital, Boston, MA, USA.
authors: Meredith A
authors: MA
authors: Benson
authors: Elizabeth A
authors: EA
authors: Ohneck
authors: Chanelle
authors: C
authors: Ryan
authors: Francis
authors: F
authors: Alonzo
authors: Hannah
authors: H
authors: Smith
authors: Apurva
authors: A
authors: Narechania
authors: Sergios-Orestis
authors: SO
authors: Kolokotronis
authors: Sarah W
authors: SW
authors: Satola
authors: Anne-Catrin
authors: AC
authors: Uhlemann
authors: Robert
authors: R
authors: Sebra
authors: Gintaras
authors: G
authors: Deikus
authors: Bo
authors: B
authors: Shopsin
authors: Paul J
authors: PJ
authors: Planet
authors: Victor J
authors: VJ
authors: Torres
mesh_terms: D001426:Bacterial Proteins / Q000096:biosynthesis / Q000235:genetics; D001427:Bacterial Toxins / Q000096:biosynthesis / Q000235:genetics; D004251:DNA Transposable Elements; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics; D019143:Evolution, Molecular; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D055624:Methicillin-Resistant Staphylococcus aureus / Q000235:genetics* / Q000254:growth & development*; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D011995:Recombination, Genetic; D012097:Repressor Proteins / Q000096:biosynthesis / Q000235:genetics; D017422:Sequence Analysis, DNA; D014774:Virulence; D037521:Virulence Factors / Q000096:biosynthesis / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; D001427:Bacterial Toxins; D004251:DNA Transposable Elements; D004269:DNA, Bacterial; D012097:Repressor Proteins; D037521:Virulence Factors; C408643:rot protein, Staphylococcus aureus