A CD-1 mouse model of infection with &lt;i&gt;Staphylococcus aureus&lt;/i&gt;: Influence of gender on infection with MRSA and MSSA isolates

Yanke, S J; Olson, Merle E.; Davies, H. Dele; Hart, David A.

doi:10.1139/cjm-46-10-920

Cited by 10 publications

(5 citation statements)

References 26 publications

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“…However, females have increased risk of mortality from SAB, with reports on MRSA and community-acquired SAB showing higher 7- and 30-day mortality rates, respectively, for female versus male patients (23, 70, 71). Consistent with this epidemiological data showing human females are more likely to die from SAB, female mice show reduced survival following intravenous S. aureus infection compared to males (72), and administration of exogenous estrogen to females further increased mortality compared to vehicle-treated controls (73). In contrast, male rabbits were more susceptible than females in a lethal subcutaneous implant infection model using a toxic shock syndrome toxin (TSST-1) producing S. aureus isolate (74).…”

Section: Discussionsupporting

confidence: 68%

Innate Sex Bias of Staphylococcus aureus Skin Infection Is Driven by α-Hemolysin

Castleman

Pokhrel

Triplett

et al. 2018

The Journal of Immunology

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Numerous studies have reported sex bias in infectious diseases, with bias direction dependent on pathogen and site of infection. is the most common cause of skin and soft tissue infections (SSTIs), yet sex bias in susceptibility to SSTI has not been described. A search of electronic health records revealed an odds ratio of 2.4 for SSTI in males versus females. To investigate the physiological basis of this bias, we compared outcomes between male and female mice in a model of dermonecrosis. Consistent with the epidemiological data, female mice were better protected against SSTI, with reduced dermonecrosis followed later by increased bacterial clearance. Protection in females was disrupted by ovariectomy and restored by short-term estrogen administration. Importantly, this sex bias was mediated by a sex-specific response to the secreted virulence factor α-hemolysin (Hla). Infection with wild-type suppressed inflammatory cytokine production in the skin of female, but not male, mice when compared with infection with an isogenic deletion mutant. This differential response was conserved following injection with Hla alone, demonstrating a direct response to Hla independent of bacterial burden. Additionally, neutrophils, essential for clearing, demonstrated sex-specific bactericidal capacity ex vivo. This work suggests that sex-specific skin innate responsiveness to Hla and neutrophil bactericidal capacity play important roles in limiting SSTI in females. Understanding the molecular mechanisms controlling this sex bias may reveal novel targets to promote host innate defense against skin infection.

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Section: Discussionsupporting

confidence: 68%

Innate Sex Bias of Staphylococcus aureus Skin Infection Is Driven by α-Hemolysin

Castleman

Pokhrel

Triplett

et al. 2018

The Journal of Immunology

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“…In our mouse S . aureus bacteremia model, the temporal distribution of the organ bacterial burden followed what has been previously documented (S4 Fig) [40, 70, 71]. Among all the examined organs, the kidney was the only niche that developed a chronic infection over time.…”

Section: Discussionsupporting

confidence: 61%

Urease is an essential component of the acid response network of Staphylococcus aureus and is required for a persistent murine kidney infection

et al. 2019

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Staphylococcus aureus causes acute and chronic infections resulting in significant morbidity. Urease, an enzyme that generates NH3 and CO2 from urea, is key to pH homeostasis in bacterial pathogens under acidic stress and nitrogen limitation. However, the function of urease in S. aureus niche colonization and nitrogen metabolism has not been extensively studied. We discovered that urease is essential for pH homeostasis and viability in urea-rich environments under weak acid stress. The regulation of urease transcription by CcpA, Agr, and CodY was identified in this study, implying a complex network that controls urease expression in response to changes in metabolic flux. In addition, it was determined that the endogenous urea derived from arginine is not a significant contributor to the intracellular nitrogen pool in non-acidic conditions. Furthermore, we found that during a murine chronic renal infection, urease facilitates S. aureus persistence by promoting bacterial fitness in the low-pH, urea-rich kidney. Overall, our study establishes that urease in S. aureus is not only a primary component of the acid response network but also an important factor required for persistent murine renal infections.

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“…All mice were housed in specific-pathogen free facilities and 8 to 12-week old age-matched female mice were used for in vitro and in vivo experiments. Because of sex-related differences in susceptibility to S. aureus (Yanke et al, 2000), only female mice were used in this study. This study was performed under strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals.…”

Section: Stars Methodsmentioning

confidence: 99%

O-Acetylation of Peptidoglycan Limits Helper T Cell Priming and Permits Staphylococcus aureus Reinfection

Sanchez

Kolar

Müller

et al. 2017

Cell Host & Microbe

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Summary Humans do not usually develop effective immunity to Staphylococcus aureus reinfection. Using a murine model that mimics human infection, we show that lack of protective immunity to S. aureus systemic reinfection is associated with robust IL-10 production and impaired protective Th17 responses. In dendritic-cell co-culture assays, priming with S. aureus promotes robust T-cell proliferation, but limits Th cells polarization and production of IL1-β and other cytokines important for Th1 and Th17 differentiation. We show that O-acetylation of peptidoglycan, a mechanism utilized by S. aureus to block bacterial cell-wall breakdown, limits the induction of pro-inflammatory signals required for optimal Th17 polarization. IL-10-deficiency in mice restores protective immunity to S. aureus infection, and adjuvancy with a staphylococcal peptidoglycan O-acetyltransferase mutant reduces IL-10, increases IL1-β, and promotes development of IL-17-dependent, Th cell-transferable protective immunity. Overall, our study suggests a mechanism whereby S. aureus modulates cytokines critical for induction of protective Th17 immunity.

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A CD-1 mouse model of infection with <i>Staphylococcus aureus</i>: Influence of gender on infection with MRSA and MSSA isolates

Cited by 10 publications

References 26 publications

Innate Sex Bias of Staphylococcus aureus Skin Infection Is Driven by α-Hemolysin

Innate Sex Bias of Staphylococcus aureus Skin Infection Is Driven by α-Hemolysin

Urease is an essential component of the acid response network of Staphylococcus aureus and is required for a persistent murine kidney infection

O-Acetylation of Peptidoglycan Limits Helper T Cell Priming and Permits Staphylococcus aureus Reinfection

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