Content area
Full text
About the Authors:
Eileen A. Larkin
Affiliations Immunology Department, Medical Research Institute of Infectious Diseases, Frederick, Maryland, United States of America, Biomedical Sciences Department, Hood College, Frederick, Maryland, United States of America
Bradley G. Stiles
* E-mail: [email protected] (BGS); [email protected] (RGU)
Affiliations Immunology Department, Medical Research Institute of Infectious Diseases, Frederick, Maryland, United States of America, Biology Department, Wilson College, Chambersburg, Pennsylvania, United States of America
Robert G. Ulrich
* E-mail: [email protected] (BGS); [email protected] (RGU)
Affiliations Immunology Department, Medical Research Institute of Infectious Diseases, Frederick, Maryland, United States of America, Biomedical Sciences Department, Hood College, Frederick, Maryland, United States of America
Introduction
Staphylococcus aureus is a common source of many diseases for both humans and domestic animals [1]. This bacterium presents a daunting medical problem due to increasing antibiotic resistance among nosocomial- and community-acquired isolates [2]–[4]. The economic burden of S. aureus upon healthcare systems around the world is substantial and new means of controlling diseases caused by this pathogen are clearly needed now [5], [6].
To gain an infective foothold, S. aureus produces several factors that facilitate adherence, interfere with a proper immune response, or otherwise alter the host microenvironment. One type of virulence factor includes the staphylococcal enterotoxins (SEs), originally distinguished by serotyping methodology [7]–[10]. These protein toxins can cause acute gastroenteritis and toxic shock syndrome. Although SEs (>20 known to date) appear distinct by amino acid sequence comparisons [11], all share common superantigen structures consisting of an N-terminal OB (oligonucleotide/oligosaccharide binding) fold and C-terminal, ubiquitin-like, beta-grasp domain. Related superantigenic proteins are also expressed by another bacterial pathogen, Streptococcus pyogenes [12]. SE cross-linking of major histocompatibility complex class II molecules (MHC II) and specific subsets of T-cell antigen receptors (TCR) activate the immune system [13]. Superantigenic effects [14] involve profound T-cell proliferation and elevated levels of the proinflammatory cytokines interferon gamma (IFNγ), interleukin 2 (IL-2), and tumor necrosis factor alpha (TNFα). Toxic shock syndrome, due to bacterial superantigen exposure, can rapidly progress to severe and intractable hypotension, multi-system failure and death.
Concerning toxin-induced diseases associated with S. aureus, the most comprehensive clinical data are available for staphylococcal toxic shock caused by toxic shock syndrome toxin-1 (TSST-1). There is a clear predisposition towards initial and recurring bouts of toxic shock syndrome among menstruating women...