Mobile Genetic Element-Encoded Cytolysin Connects Virulence to Methicillin Resistance in MRSA

Queck, Shu Y.; Khan, Burhan A.; Rong Wang; Bach, Thanh-Huy L.; Kretschmer, Dorothee; Liang Chen; Kreiswirth, Barry N.; Peschel, Andreas; DeLeo, Frank R.; Otto, Michael
July 2009
PLoS Pathogens;Jul2009, Vol. 5 Issue 7, p1
Academic Journal
Bacterial virulence and antibiotic resistance have a significant influence on disease severity and treatment options during bacterial infections. Frequently, the underlying genetic determinants are encoded on mobile genetic elements (MGEs). In the leading human pathogen Staphylococcus aureus, MGEs that contain antibiotic resistance genes commonly do not contain genes for virulence determinants. The phenol-soluble modulins (PSMs) are staphylococcal cytolytic toxins with a crucial role in immune evasion. While all known PSMs are core genome-encoded, we here describe a previously unidentified psm gene, psm-mec, within the staphylococcal methicillin resistance-encoding MGE SCCmec. PSM-mec was strongly expressed in many strains and showed the physico-chemical, pro-inflammatory, and cytolytic characteristics typical of PSMs. Notably, in an S. aureus strain with low production of core genome-encoded PSMs, expression of PSM-mec had a significant impact on immune evasion and disease. In addition to providing high-level resistance to methicillin, acquisition of SCCmec elements encoding PSM-mec by horizontal gene transfer may therefore contribute to staphylococcal virulence by substituting for the lack of expression of core genome-encoded PSMs. Thus, our study reveals a previously unknown role of methicillin resistance clusters in staphylococcal pathogenesis and shows that important virulence and antibiotic resistance determinants may be combined in staphylococcal MGEs.


Related Articles

  • SaeR Binds a Consensus Sequence within Virulence Gene Promoters to Advance USA300 Pathogenesis. Nygaard, Tyler K.; Pallister, Kyler B.; Ruzevich, Peter; Griffith, Shannon; Vuong, Cuong; Voyich, Jovanka M. // Journal of Infectious Diseases;1/15/2010, Vol. 201 Issue 2, p241 

    This investigation examines the role of the SaeR/S 2-component system in USA300, a prominent circulating clone of community-associated methicillin-resistant Staphylococcus aureus. Using a saeR/S isogenic deletion mutant of USA300 (USA300ΔsaeR/S) in murine models of sepsis and soft-tissue...

  • Global spread of vancomycin-resistant Enterococcus faecium from distinct nosocomial genetic complex. Willems, Rob J. L.; Top, Janetta; Van Santen, Marga; Robinson, D. Ashley; Coque, Teresa M.; Baquero, Fernando; Grundmann, Hajo; Bonten, Marc J. M. // Emerging Infectious Diseases;Jun2005, Vol. 11 Issue 6, p821 

    Vancomycin-resistant enterococci (VRE) have caused hospital outbreaks worldwide, and the vancomycin-resistance gene (vanA) has crossed genus boundaries to methicillin-resistant Staphylococcus aureus. Spread of VRE, therefore, represents an immediate threat for patient care and creates a...

  • Variability of SCC mec in the Zurich area. Ender, M.; Burger, S.; Sokoli, A.; Zbinden, R.; Berger-Bächi, B.; Heusser, R.; Senn, M. M.; McCallum, N. // European Journal of Clinical Microbiology & Infectious Diseases;Jun2009, Vol. 28 Issue 6, p647 

    A periodic survey of methicillin-resistant Staphylococcus aureus (MRSA) in Zurich in 2004 and 2006 revealed a consistently low prevalence of MRSA. SCC mec and ccr typing showed fluctuations in the proportions of SCC mec types and in the carriage of mobile virulence determinants. Together with...

  • Comparative Analysis of Virulence and Toxin Expression of Global Community-Associated Methicillin-Resistant Staphylococcus aureus Strains. Min Li; Cheung, Gordon Y. C.; Jinhui Hu; Decheng Wang; Hwang-Soo Joo; DeLeo, Frank R.; Otto, Michael // Journal of Infectious Diseases;12/15/2010, Vol. 202 Issue 12, p1866 

    The current pandemic of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) skin infections is caused by several genetically unrelated clones. Here, we analyzed virulence of globally occurring CA-MRSA strains in a rabbit skin infection model. We used rabbits because...

  • Beyond the Chromosome: The Prevalence of Unique Extra-Chromosomal Bacteriophages with Integrated Virulence Genes in Pathogenic Staphylococcus aureus. Utter, Bryan; Deutsch, Douglas R.; Schuch, Raymond; Winer, Benjamin Y.; Verratti, Kathleen; Bishop-Lilly, Kim; Sozhamannan, Shanmuga; Fischetti, Vincent A. // PLoS ONE;Jun2014, Vol. 9 Issue 6, p1 

    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,...

  • Genomic characterization of ribitol teichoic acid synthesis in Staphylococcus aureus: genes, genomic organization and gene duplication. Qian, Ziliang; Yin, Yanbin; Zhang, Yong; Lu, Lingyi; Li, Yixue; Jiang, Ying // BMC Genomics;2006, Vol. 7, p1 

    Background: Staphylococcus aureus or MRSA (Methicillin Resistant S. aureus), is an acquired pathogen and the primary cause of nosocomial infections worldwide. In S. aureus, teichoic acid is an essential component of the cell wall, and its biosynthesis is not yet well characterized. Studies in...

  • Subtle genetic changes enhance virulence of methicillin resistant and sensitive Staphylococcus aureus. Highlander, Sarah K.; Hultén, Kristina G.; Xiang Qin; Huaiyang Jiang; Yerrapragada, Shailaja; Mason Jr., Edward O.; Yue Shang; Williams, Tiffany M.; Fortunov, Régine M.; Yamei Liu; Igboeli, Okezie; Petrosino, Joseph; Tirumalai, Madhan; Uzman, Akif; Fox, George E.; Cardenas, Ana Maria; Muzny, Donna M.; Hemphill, Lisa; Yan Ding; Dugan, Shannon // BMC Microbiology;2007, Vol. 7, p99 

    Background: Community acquired (CA) methicillin-resistant Staphylococcus aureus (MRSA) increasingly causes disease worldwide. USA300 has emerged as the predominant clone causing superficial and invasive infections in children and adults in the USA. Epidemiological studies suggest that USA300 is...

  • Virulence Gene Expression in Human Community-Acquired Staphylococcus aureus Infection. Loughman, Jennifer A.; Fritz, Stephanie A.; Storch, Gregory A.; Hunstad, David A. // Journal of Infectious Diseases;2/1/2009, Vol. 198 Issue 3, p294 

    Isolates of methicillin-resistant Staphylococcus aureus (MRSA) were once linked uniformly with hospitalassociated infections; however, community-acquired MRSA (CA-MRSA) now represents an emerging threat worldwide. To examine the association of differential virulence gene expression with outcomes...

  • Illness Severity in Community-Onset Invasive Staphylococcus aureus Infection and the Presence of Virulence Genes. Wehrhahn, Michael C.; Robinson, J. Owen; Pascoe, Elaine M.; Coombs, Geoffrey W.; Pearson, Julie C.; O'Brien, Frances G.; Tan, Hui-Leen; New, David; Salvaris, Patrick; Salvaris, Ross; Murray, Ronan J. // Journal of Infectious Diseases;Jun2012, Vol. 205 Issue 12, p1840 

    Background. It is uncertain whether particular clones causing invasive community-onset methicillin-resistant and methicillin-sensitive Staphylococcus aureus (cMRSA/cMSSA) infection differ in virulence.Methods. Invasive cMRSA and cMSSA cases were prospectively identified. Principal component...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics