title: A type III-like restriction endonuclease functions as a major barrier to horizontal gene transfer in clinical Staphylococcus aureus strains.
abstract: Staphylococcus aureus is an versatile pathogen that can cause life-threatening infections. Depending on the clinical setting, up to 50% of S. aureus infections are caused by methicillin-resistant strains (MRSA) that in most cases are resistant to many other antibiotics, making treatment difficult. The emergence of community-acquired MRSA drastically changed the picture by increasing the risk of MRSA infections. Horizontal transfer of genes encoding for antibiotic resistance or virulence factors is a major concern of multidrug-resistant S. aureus infections and epidemiology. We identified and characterized a type III-like restriction system present in clinical S. aureus strains that prevents transformation with DNA from other bacterial species. Interestingly, our analysis revealed that some clinical MRSA strains are deficient in this restriction system, and thus are hypersusceptible to the horizontal transfer of DNA from other species, such as Escherichia coli, and could easily acquire a vancomycin-resistance gene from enterococci. Inactivation of this restriction system dramatically increases the transformation efficiency of clinical S. aureus strains, opening the field of molecular genetic manipulation of these strains using DNA of exogenous origin.
authors.affiliation: Department of Microbiology and Molecular Medicine, University Medical Center, University of Geneva, 1211 Geneva 4, Switzerland.
authors.forename: Anna R
authors.initials: AR
authors.lastname: Corvaglia
authors.forename: Patrice
authors.initials: P
authors.lastname: François
authors.forename: David
authors.initials: D
authors.lastname: Hernandez
authors.forename: Karl
authors.initials: K
authors.lastname: Perron
authors.forename: Patrick
authors.initials: P
authors.lastname: Linder
authors.forename: Jacques
authors.initials: J
authors.lastname: Schrenzel
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D004269:DNA, Bacterial / Q000235:genetics; D015253:Deoxyribonucleases, Type I Site-Specific / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015263:Deoxyribonucleases, Type III Site-Specific / Q000235:genetics / Q000378:metabolism*; D013293:Enterococcus faecalis / Q000201:enzymology / Q000235:genetics; D004926:Escherichia coli / Q000235:genetics; D018390:Gene Targeting; D022761:Gene Transfer, Horizontal; D005798:Genes, Bacterial; D006801:Humans; D016106:Methicillin Resistance / Q000235:genetics; D055624:Methicillin-Resistant Staphylococcus aureus / Q000201:enzymology / Q000235:genetics / Q000302:isolation & purification; D008969:Molecular Sequence Data; D010957:Plasmids / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D013211:Staphylococcus aureus / Q000201:enzymology* / Q000235:genetics* / Q000302:isolation & purification
chemical_list: D004269:DNA, Bacterial; D015253:Deoxyribonucleases, Type I Site-Specific; D015263:Deoxyribonucleases, Type III Site-Specific