MRSA epidemic linked to a quickly spreading colonization and virulence determinant

The molecular processes underlying epidemic waves of methicillin-resistant Staphylococcus aureus (MRSA) infection are poorly understood. Although a major role has been attributed to the acquisition of virulence determinants by horizontal gene transfer, there are insufficient epidemiological and functional data supporting that concept. We here report the spread of clones containing a previously extremely rare mobile genetic element–encoded gene, sasX. We demonstrate that sasX has a key role in MRSA colonization and pathogenesis, substantially enhancing nasal colonization, lung disease and abscess formation and promoting mechanisms of immune evasion. Moreover, we observed the recent spread of sasX from sequence type 239 (ST239) to invasive clones belonging to other sequence types. Our study identifies sasX as a quickly spreading crucial determinant of MRSA pathogenic success and a promising target for therapeutic interference. Our results provide proof of principle that horizontal gene transfer of key virulence determinants drives MRSA epidemic waves.

[1]  K. Ko,et al.  Distribution of Major Genotypes among Methicillin-Resistant Staphylococcus aureus Clones in Asian Countries , 2005, Journal of Clinical Microbiology.

[2]  Gina Pugliese,et al.  Nasal Carriage as a Source of Staphylococcus aureus Bacteremia , 2001, Infection Control & Hospital Epidemiology.

[3]  Adeline R. Whitney,et al.  Targeting of alpha-hemolysin by active or passive immunization decreases severity of USA300 skin infection in a mouse model. , 2010, The Journal of infectious diseases.

[4]  Alex van Belkum,et al.  The role of nasal carriage in Staphylococcus aureus infections. , 2005, The Lancet. Infectious diseases.

[5]  Timothy Foster,et al.  Key Role for Clumping Factor B in Staphylococcus aureus Nasal Colonization of Humans , 2008, PLoS medicine.

[6]  A. Kumar Invasive Methicillin-Resistant Staphylococcus aureus Infections in the United States , 2008 .

[7]  J. Niu,et al.  Molecular Evidence for Spread of Two Major Methicillin-Resistant Staphylococcus aureus Clones with a Unique Geographic Distribution in Chinese Hospitals , 2008, Antimicrobial Agents and Chemotherapy.

[8]  F. DeLeo,et al.  Reemergence of antibiotic-resistant Staphylococcus aureus in the genomics era. , 2009, The Journal of clinical investigation.

[9]  M. Kuroda,et al.  The emergence and evolution of methicillin-resistant Staphylococcus aureus. , 2001, Trends in microbiology.

[10]  M. Otto,et al.  Staphylococcal Biofilms , 2018, Microbiology spectrum.

[11]  R. Novick,et al.  Complete nucleotide sequence of pT181, a tetracycline-resistance plasmid from Staphylococcus aureus. , 1983, Plasmid.

[12]  Roberta B Carey,et al.  Invasive methicillin-resistant Staphylococcus aureus infections in the United States. , 2007, JAMA.

[13]  F. Götz,et al.  Characterization of a sucrase gene from Staphylococcus xylosus , 1993, Journal of bacteriology.

[14]  Adeline R. Whitney,et al.  Is Panton-Valentine leukocidin the major virulence determinant in community-associated methicillin-resistant Staphylococcus aureus disease? , 2006, The Journal of infectious diseases.

[15]  Å. Nilsdotter-Augustinsson,et al.  Staphylococcus epidermidis surface protein I (SesI): a marker of the invasive capacity of S. epidermidis? , 2009, Journal of medical microbiology.

[16]  Roberta B Carey,et al.  Methicillin-resistant S. aureus infections among patients in the emergency department. , 2006, The New England journal of medicine.

[17]  T. Foster,et al.  Staphylococcus aureus clumping factor B (ClfB) promotes adherence to human type I cytokeratin 10: implications for nasal colonization , 2002, Cellular microbiology.

[18]  T. Foster,et al.  Surface proteins that promote adherence of Staphylococcus aureus to human desquamated nasal epithelial cells , 2009, BMC Microbiology.

[19]  R. Macaden,et al.  Genotyping of Methicillin-Resistant Staphylococcus aureus Strains from Two Hospitals in Bangalore, South India , 2005, Journal of Clinical Microbiology.

[20]  M. Otto,et al.  Bacterial evasion of antimicrobial peptides by biofilm formation. , 2006, Current topics in microbiology and immunology.

[21]  A. Cochran,et al.  Molecular classification of melanomas and nevi using gene expression microarray signatures and formalin-fixed and paraffin-embedded tissue , 2009, Modern Pathology.

[22]  M. Quail,et al.  Genome Sequence of a Recently Emerged, Highly Transmissible, Multi-Antibiotic- and Antiseptic-Resistant Variant of Methicillin-Resistant Staphylococcus aureus, Sequence Type 239 (TW) , 2009, Journal of bacteriology.

[23]  O. Schneewind,et al.  Allelic replacement in Staphylococcus aureus with inducible counter-selection. , 2006, Plasmid.

[24]  M. O'Reilly,et al.  Expression of the cloned toxic shock syndrome toxin 1 gene (tst) in vivo with a rabbit uterine model , 1985, Infection and immunity.

[25]  A. Kennedy,et al.  Identification of novel cytolytic peptides as key virulence determinants for community-associated MRSA , 2007, Nature Medicine.

[26]  T. Foster,et al.  Surface protein adhesins of Staphylococcus aureus. , 1998, Trends in microbiology.

[27]  H Stammer,et al.  Nasal Carriage as a Source of Staphylococcus aureus Bacteremia , 2001 .

[28]  B. Neumeister,et al.  Role of teichoic acids in Staphylococcus aureus nasal colonization, a major risk factor in nosocomial infections , 2004, Nature Medicine.

[29]  James M. Musser,et al.  spa Typing Method for Discriminating among Staphylococcus aureus Isolates: Implications for Use of a Single Marker To Detect Genetic Micro- and Macrovariation , 2004, Journal of Clinical Microbiology.

[30]  M. Achtman,et al.  Multilocus sequence typing: a portable approach to the identification of clones within populations of pathogenic microorganisms. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[31]  A. Tomasz,et al.  Frequent Recovery of a Single Clonal Type of Multidrug-Resistant Staphylococcus aureus from Patients in Two Hospitals in Taiwan and China , 2003, Journal of Clinical Microbiology.

[32]  Boyang Cao,et al.  Complete Genome Sequence of Staphylococcus aureus T0131, an ST239-MRSA-SCCmec Type III Clone Isolated in China , 2011, Journal of bacteriology.

[33]  F. Lowy Antimicrobial resistance: the example of Staphylococcus aureus. , 2003, The Journal of clinical investigation.

[34]  E. Fischer,et al.  Quorum-sensing control of biofilm factors in Staphylococcus epidermidis. , 2003, The Journal of infectious diseases.

[35]  Henry F. Chambers,et al.  Waves of resistance: Staphylococcus aureus in the antibiotic era , 2009, Nature Reviews Microbiology.

[36]  T. Foster Immune evasion by staphylococci , 2005, Nature Reviews Microbiology.

[37]  M. Otto,et al.  Impact of the agr quorum-sensing system on adherence to polystyrene in Staphylococcus aureus. , 2000, The Journal of infectious diseases.

[38]  M. Enright,et al.  Characterization of Isolates of Methicillin-Resistant Staphylococcus aureus from Hong Kong by Phage Typing, Pulsed-Field Gel Electrophoresis, and Fluorescent Amplified-Fragment Length Polymorphism Analysis , 2003, Journal of Clinical Microbiology.

[39]  G. Sensabaugh,et al.  Roles of 34 virulence genes in the evolution of hospital- and community-associated strains of methicillin-resistant Staphylococcus aureus. , 2006, The Journal of infectious diseases.

[40]  Julian Parkhill,et al.  Evolution of MRSA During Hospital Transmission and Intercontinental Spread , 2010, Science.