Proinflammatory Exoprotein Characterization of Toxic Shock Syndrome Staphylococcus aureus

被引:33
|
作者
Lin, Ying-Chi [1 ]
Anderson, Michele J. [1 ]
Kohler, Petra L. [2 ]
Strandberg, Kristi L. [2 ]
Olson, Michael E. [3 ]
Horswill, Alexander R. [3 ]
Schlievert, Patrick M. [2 ]
Peterson, Marnie L. [1 ,2 ]
机构
[1] Univ Minnesota, Coll Pharm, Dept Expt & Clin Pharmacol, Minneapolis, MN 55455 USA
[2] Univ Minnesota, Sch Med, Dept Microbiol, Minneapolis, MN 55455 USA
[3] Univ Iowa, Dept Microbiol, Iowa City, IA 52242 USA
关键词
METHICILLIN-RESISTANT; UNITED-STATES; ENTEROTOXIN-B; ALPHA-TOXIN; VIRULENCE; EXPRESSION; PNEUMONIA; INFECTION; HEMOLYSIN; MODEL;
D O I
10.1021/bi200435n
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Pulsed-field gel electrophoresis (PFGE) clonal type USA200 is the most widely disseminated Staphylococcus aureus colonizer of the nose and is a major cause of toxic shock syndrome (TSS). Exoproteins derived from these organisms have been suggested to contribute to their colonization and causation of human diseases but have not been well-characterized. Two representative S. aureus USA200 isolates, MNPE (alpha-toxin positive) and CDC587 (alpha-toxin mutant), isolated from pulmonary post-influenza TSS and menstrual vaginal TSS, respectively, were evaluated. Biochemical, immuno-biological, and cell-based assays, including mass spectrometry, were used to identify key exoproteins derived from the strains that are responsible for proinflammatory and cytotoxic activity on human vaginal epithelial cells. Exoproteins associated with virulence were produced by both strains, and cytolysins (alpha-toxin and gamma-toxin), superantigens, and proteases were identified as the major exoproteins, which caused epithelial cell inflammation and cytotoxicity. Exoprotein fractions from MNPE were more proinflammatory and cytotoxic than those from CDC587 due to high concentrations of alpha-toxin. CDC587 produced a small amount of alpha-toxin, despite the presence of a stop codon (TAG) at codon 113. Additional exotoxin identification studies of USA200 strain [S. aureus MN8 (alpha-toxin mutant)] confirmed that MN8 also produced low levels of alpha-toxin despite the same stop codon. The differences observed in virulence factor profiles of two USA200 strains provide insight into environmental factors that select for specific virulence factors. Cytolysins, superantigens, and proteases were identified as potential targets, where toxin neutralization may prevent or diminish epithelial damage associated with S. aureus.
引用
收藏
页码:7157 / 7167
页数:11
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