Understanding the Molecular Pathogenesis of Methicillin-Resistant Staphylococcus aureus

Staphylococcus aureus has been referred to as the “persistent pathogen” [1, 2] owing to its high prevalence for decades, its cause of a significant burden of disease, and its ability to cause a wide spectrum of clinical infections at various sites, including skin and soft tissue, bone and joint, heart valves, blood stream, and cerebrospinal fluid. These organisms possess numerous toxins and virulence factors that may account for their virulence and ability to evade host defenses [3, 4]. The acquisition by S. aureus of the staphylococcal cassette chromosome containing the mecA gene (SCCmecA), which encodes for methicillin resistance, has added to its armamentarium and increased the difficulty in its eradication in human infections [5,6]. The epidemiology of methicillin-resistant S. aureus (MRSA) is closely intertwined with that of methicillin-susceptible S. aureus (MSSA), and has become more complex with the recognition of healthcare-associated, healthcare-associated community-onset, and community-associated (CA) MRSA strains [4, 7, 8]. With the advent of numerous molecular typing methods has come an enhanced understanding of the complex evolution and epidemiology of MRSA [5, 9, 10]. There is a predominance of multilocus sequence type ST5 or clonal complex (CC) 5, with pulsed-field gel electrophoresis (PFGE) type USA100 as the most common healthcare-associated strains and ST8 or CC8 PFGE USA300 as the most common among communityassociated strains [8, 9]. Many of the MRSA strains are thought to have originated from predominant MSSA strains that acquired SCCmecA [6, 11]. The genotype classifications, while critical in elucidating the evolution, transmission, and epidemiology of both MSSA and MRSA infections in populations at risk, have only recently been recognized as potential predictors of specific clinical infections. As examples, in a large international data set of MSSA isolates, isolates causing infective endocarditis were more likely to be CC33 and to contain various adhesins and enterotoxins [12]. Furthermore, an analysis of both MSSA and MRSA isolates from one US academic medical center demonstrated that CC5 and CC30 strains were responsible for hematogenous complications of infection [13]. A predominant Asian strain of MRSA, ST239, was recently responsible for a large intensive care unit outbreak in London, and was highly associated with vascular access device-related bacteremia [14]. A related predominant Brazilian clonal complex of MRSA has been demonstrated to have enhanced ability to produce biofilm and adhere to and invade airway epithelial cells, properties that may promote its nosocomial transmission and ability to cause pneumonia [15]. In a study of patients with S. aureus bacteremia, CC15 was associated with 30-day mortality, and CC22 with osteoarticular infections [16]. These and other findings suggest that clonal typing may be a potential predictor of specific clinical infections. Additional research is needed to analyze the specific features and characteristics of individual clonal types that could be responsible for their predilection to cause or associate with specific types of clinical infections. One very important area of future research is linking the profiles of S. aureus toxins and virulence factors to specific genotypes. Because of their physiologic functions, specific toxins and virulence factors are probably the key to and the best predictors of important infection [3]. One of the most commonly cited factors in MRSA infections has been the PantonValentine leukocidin (PVL), a toxin [4, 17] that is found in many strains of CAMRSA and is cytotoxic to human and rabbit monocytes and macrophages and to human polymorphonuclear leukocytes. Received 11 October 2013; accepted 15 October 2013; electronically published 26 October 2013. Correspondence: Kurt B. Stevenson, MD, MPH, Division of Infectious Diseases, Department of Internal Medicine, College of Medicine, Ohio State University, N-1122 Doan Hall, 410 West 10th Ave, Columbus, OH 43210 (kurt.stevenson@osumc.edu). The Journal of Infectious Diseases 2014;209:488–90 © The Author 2013. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals. permissions@oup.com. DOI: 10.1093/infdis/jit557