Virulence regulation in<i>Staphylococcus aureus</i>: the need for in vivo analysis of virulence factor regulation

Pragman, Alexa A.; Schlievert, Patrick M.

doi:10.1016/j.femsim.2004.05.005

Cited by 76 publications

(55 citation statements)

References 50 publications

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“…This finding is consistent with studies on the regulation of SEs, which have also revealed that the in vivo expression of SEs may not correlate with in vitro observations (26,29). One reason could be that the pathogen burden and/or the in vivo growth conditions potentially affect toxin production (30)(31)(32).…”

Section: Discussionsupporting

confidence: 86%

Detection and Measurement of Staphylococcal Enterotoxin-Like K (SEl-K) Secretion by Staphylococcus aureus Clinical Isolates

et al. 2014

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SEl-K is commonly present in more than half of all Staphylococcus aureus clinical isolates and is present in almost all USA300 community-acquired methicillin-resistant S. aureus (CA-MRSA) isolates. Sequencing of the sel-k gene in over 20 clinical isolates and comparative analysis with all 14 published sel-k sequences indicate that there are at least 6 variants of the sel-k gene, including one that is conserved among all examined USA300 strains. Additionally, we have developed a highly sensitive enzyme-linked immunosorbent assay (ELISA) that specifically detects and measures SEl-K protein in culture supernatants and biological fluids. Quantification of in vitro SEl-K secretion by various S. aureus isolates using this novel capture ELISA revealed detectable amounts of SEl-K secretion by all isolates, with the highest secretion levels being exhibited by MRSA strains that coexpress SEB. In vivo secretion was measured in a murine thigh abscess model, where similar levels of SEl-K accumulation were noted regardless of whether the infecting strain exhibited high or low secretion of SEl-K in vitro. We conclude that SEl-K is commonly expressed in the setting of staphylococcal infection, in significant amounts. SEl-K should be further explored as a target for passive immunotherapy against complicated S. aureus infection. Staphylococcus aureus can express a large and diverse repertoire of virulence factors, including many different surface proteins, enzymes, and secreted toxins (1). Among the most potent of these virulence factors are the members of a family of secreted, heatstable proteins known as enterotoxins. More than 20 staphylococcal enterotoxins (SEs) have been discovered that demonstrate superantigenic (SAg) properties against T cells (2, 3). Superantigens can activate 20% to 50% of the T cell population by bypassing the traditional pathway of major histocompatibility complex (MHC)-dependent presentation of antigens to T cell receptors (TCRs). Instead, superantigens bind simultaneously to MHC class II (MHC-II) and TCRs, outside their antigen-binding groove, resulting in an excessive inflammatory response that can lead to toxic shock, multiorgan failure, and death. Superantigens are also associated with other immune-mediated diseases, including Kawasaki disease, atopic dermatitis, and chronic rhinosinusitis (4).The classical superantigens toxic shock syndrome toxin 1 (TSST-1), SEA, and SEB have been extensively studied due to their causative roles in toxic shock syndrome and food poisoning (5). However, advancements in sequencing methodologies have enabled the discovery of many more SEs whose roles in pathogenesis remain unknown (6). One of these toxins, SEl-K, has been shown to exhibit superantigenic properties, including V␤-specific T cell activation, pyrogenicity, emesis, and lethality in primates (7-9). Epidemiological studies have demonstrated the SEl-K-encoding genes to be among the most common SE genes in S. aureus clinical isolates (10-14). Additionally, SEl-K is the only SE gene to our knowledge that is si...

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Section: Discussionsupporting

confidence: 86%

Detection and Measurement of Staphylococcal Enterotoxin-Like K (SEl-K) Secretion by Staphylococcus aureus Clinical Isolates

et al. 2014

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“…Readers are encouraged to read important reviews that discuss global regulatory pathways in detail (58)(59)(60).…”

Section: The Superantigen Familymentioning

confidence: 99%

Staphylococcal and Streptococcal Superantigen Exotoxins

et al. 2013

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SUMMARY This review begins with a discussion of the large family of Staphylococcus aureus and beta-hemolytic streptococcal pyrogenic toxin T lymphocyte superantigens from structural and immunobiological perspectives. With this as background, the review then discusses the major known and possible human disease associations with superantigens, including associations with toxic shock syndromes, atopic dermatitis, pneumonia, infective endocarditis, and autoimmune sequelae to streptococcal illnesses. Finally, the review addresses current and possible novel strategies to prevent superantigen production and passive and active immunization strategies.

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“…For example, standard adherence experiments, including our experiments, are conducted under static conditions, whereas flow conditions were shown to have a notable effect on adherence phenotypes (40). There has been increasing interest in how the regulation via agr works in vivo (33), and remarkable differences in regulation, and consequently in the expression of virulence factors, between experimental and human infection and in vitro conditions have been found (2,11,20,47). In particular, a recent study showed that the differences between in vitro and in vivo conditions involve the regulation of FnBPA by both the global regulon genes saeRS and the sigB gene (3).…”

Section: Fig 3 Adherence Of S Aureus Carriage and Infection Isolatmentioning

confidence: 99%

Natural Variability of In Vitro Adherence to Fibrinogen and Fibronectin Does Not Correlate with In Vivo Infectivity of Staphylococcus aureus

et al. 2010

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Adherence to fibrinogen and fibronectin plays a crucial role in Staphylococcus aureus experimental endocarditis. Previous genetic studies have shown that infection and carriage isolates do not systematically differ in their virulence-related genes, including genes conferring adherence, such as clfA and fnbA. We set out to determine the range of adherence phenotypes in carriage isolates of S. aureus, to compare the adherence of these isolates to the adherence of infection isolates, and to determine the relationship between adherence and infectivity in a rat model of experimental endocarditis. A total of 133 healthy carriage isolates were screened for in vitro adherence to fibrinogen and fibronectin, and 30 isolates were randomly chosen for further investigation. These 30 isolates were compared to 30 infective endocarditis isolates and 30 blood culture isolates. The infectivities of the carriage isolates, which displayed either extremely low or high adherence to fibrinogen and fibronectin, were tested using a rat model of experimental endocarditis. The levels of adherence to both fibrinogen and fibronectin were very similar for isolates from healthy carriers and members of the two groups of infection isolates. All three groups of isolates showed a wide range of adherence to fibrinogen and fibronectin. Moreover, the carriage isolates that showed minimal adherence and the carriage isolates that showed strong adherence had the same infectivity in experimental endocarditis. Adherence was proven to be important for pathogenesis in experimental endocarditis, but even the least adherent carriage strains had the ability to induce infection. We discuss the roles of differential gene expression, human host factors, and gene redundancy in resolving this apparent paradox.

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Virulence regulation inStaphylococcus aureus: the need for in vivo analysis of virulence factor regulation

Cited by 76 publications

References 50 publications

Detection and Measurement of Staphylococcal Enterotoxin-Like K (SEl-K) Secretion by Staphylococcus aureus Clinical Isolates

Detection and Measurement of Staphylococcal Enterotoxin-Like K (SEl-K) Secretion by Staphylococcus aureus Clinical Isolates

Staphylococcal and Streptococcal Superantigen Exotoxins

Natural Variability of In Vitro Adherence to Fibrinogen and Fibronectin Does Not Correlate with In Vivo Infectivity of Staphylococcus aureus

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