Epidermal Growth Factor Receptor Signaling Enhances the Proinflammatory Effects of Staphylococcus aureus Gamma-Toxin on the Mucosa

Gillman, Aaron Nicholas; Breshears, Laura M.; Kistler, Charles K.; Finnegan, Patrick M.; Torres, Victor J.; Schlievert, Patrick M.; Peterson, Marnie L.

doi:10.3390/toxins9070202

Cited by 7 publications

(4 citation statements)

References 41 publications

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“…SAgs, together with the leucocidins, could contribute to mucosal epithelial barrier disruption. For example, direct damage and inflammation to the vaginal epithelium can be induced by α-toxin (Hla) and γ-toxin (both HlgAB and HlgCB), potentially contributing to the mTSS disease processes [ 157 , 158 ]. In the case of Hla, expression of this toxin was shown to augment the translocation of TSST-1 in a porcine ex vivo vaginal epithelial model, which would allow TSST-1 to induce further inflammation once across the epithelium [ 158 ].…”

Section: Superantigens In S Aureus Pathogenesimentioning

confidence: 99%

Manipulation of Innate and Adaptive Immunity by Staphylococcal Superantigens

2018

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Staphylococcal superantigens (SAgs) constitute a family of potent exotoxins secreted by Staphylococcus aureus and other select staphylococcal species. SAgs function to cross-link major histocompatibility complex (MHC) class II molecules with T cell receptors (TCRs) to stimulate the uncontrolled activation of T lymphocytes, potentially leading to severe human illnesses such as toxic shock syndrome. The ubiquity of SAgs in clinical S. aureus isolates suggests that they likely make an important contribution to the evolutionary fitness of S. aureus. Although the apparent redundancy of SAgs in S. aureus has not been explained, the high level of sequence diversity within this toxin family may allow for SAgs to recognize an assorted range of TCR and MHC class II molecules, as well as aid in the avoidance of humoral immunity. Herein, we outline the major diseases associated with the staphylococcal SAgs and how a dysregulated immune system may contribute to pathology. We then highlight recent research that considers the importance of SAgs in the pathogenesis of S. aureus infections, demonstrating that SAgs are more than simply an immunological diversion. We suggest that SAgs can act as targeted modulators that drive the immune response away from an effective response, and thus aid in S. aureus persistence.

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Section: Superantigens In S Aureus Pathogenesimentioning

confidence: 99%

Manipulation of Innate and Adaptive Immunity by Staphylococcal Superantigens

2018

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“…Pathway analysis suggests the possible involvement of ErbB1 internalization and Arf6 signaling. Both of these pathways have been associated with cellular bacterial invasion [72][73][74] . While the gene expression response to 30,000 CFU overlapped with and therefore appeared related to that of the 300 CFU experiments, the importance of PPP3CA (and of SYT1, which was also a highly connected hub in the network), along with the pathway analysis, suggests that the majority of the response was related to changes in neuron and neurotransmitter function.…”

Section: Discussionmentioning

confidence: 99%

Transfer of oral bacteria to the fetus during late gestation

Rodriguez

Paul

et al. 2021

Sci Rep

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The fetus develops in a privileged environment, as the placenta serves as both a gateway for nutrients and a barrier for pathogen transfer to the fetus. Regardless, recent evidence suggests the presence of bacterial DNA in both placenta and fetus, and we have reported that DNA and protein from small numbers of bacteria gain access to the fetus from the maternal bloodstream. Other routes of environmental bacterial transfer from the mother to fetus remain unknown, as well as the physiological relevance of their presence. In these experiments, we examine multiple routes by which bacterial cellular components can enter the fetus and the fetal response to influx of bacterial DNA and protein. We inoculated maternal sheep with genetically-labeled S. aureus (Staphylococcus aureus) using three routes: intravenously, orally, and intra-vaginally. The inoculum did not produce sepsis or fever in the ewes, therefore mimicking incidental exposure to bacteria during pregnancy. 3–5 days post inoculation, we assessed the presence of bacterial components in the fetal tissues and analyzed fetal brain tissue to identify any alterations in gene expression. Our results demonstrate that components of bacteria that were introduced into the maternal mouth were detected in the fetal brain and that they stimulated changes in gene expression. We conclude that an oral route of transmission is relevant for transfer of bacterial cellular components to the fetus.

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“…The Schlievert laboratory also maintains highly purified β-toxin ( 39 ), δ-toxin (synthesized), bicomponent γ-toxins ( 40 ), ɛ-toxin ( 41 ), and PSM-α3 toxin (synthesized). All of these hemolysins have been determined in the Schlievert laboratory to be lytic to rabbit erythrocytes, validating the use of α-toxin as the experimental standard for determination of total hemolysin production as necessary.…”

Section: Methodsmentioning

confidence: 99%

Host Cationic Antimicrobial Molecules Inhibit S. aureus Exotoxin Production

Schlievert

Kilgore

Beck

et al. 2023

mSphere

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Staphylococcus aureus causes large numbers of both relatively benign and serious human infections, which are mediated in large part by the organisms’ secreted exotoxins. Since 1921, it has been known that lysozyme and, as shown later in the 1900s, other innate immune peptides, including human neutrophil α-defensin-1 (HNP-1) and human β-defensin 1 (HBD-1), are either not antistaphylococcal or are only weakly inhibitory to growth.

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Epidermal Growth Factor Receptor Signaling Enhances the Proinflammatory Effects of Staphylococcus aureus Gamma-Toxin on the Mucosa

Cited by 7 publications

References 41 publications

Manipulation of Innate and Adaptive Immunity by Staphylococcal Superantigens

Manipulation of Innate and Adaptive Immunity by Staphylococcal Superantigens

Transfer of oral bacteria to the fetus during late gestation

Host Cationic Antimicrobial Molecules Inhibit S. aureus Exotoxin Production

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