Intravaginal cooling provides symptom relief in women with vulvovaginal candidiasis and reduces immunopathology in an accompanying mouse model.

Background: Vulvovaginal candidiasis (VVC), caused primarily by Candida albicans, is currently treated with either prescription or over-the-counter antifungal drugs, often with variable efficacy and relapses. New and improved therapeutic strategies, including drug-free treatment alternatives, are needed. Upon overgrowth or environmental triggers, C.

A fungal metabolic regulator underlies infectious synergism during - aureus intra-abdominal co-infection.

and are two commonly associated pathogens that cause nosocomial infections with high morbidity and mortality. Our prior and current work using a murine model of polymicrobial intra-abdominal infection (IAI) uncovered synergistic lethality that was driven by -induced upregulation of functional ⍺-toxin leading to polymicrobial sepsis and organ damage. In order to determine the candidal effector(s) mediating enhanced virulence, an unbiased screen of transcription factor mutants was undertaken and revealed that Δ/Δ failed to drive augmented ⍺-toxin or lethal synergism during co-infection.

Protection against lethal sepsis following immunization with species varies by isolate and inversely correlates with bone marrow tissue damage.

Protection against lethal ()/ () intra-abdominal infection (IAI)-mediated sepsis can be achieved by a novel form of trained innate immunity (TII) involving Gr-1+ myeloid-derived suppressor cells (MDSCs) that are induced by inoculation (immunization) with low virulence species [i.e., ()] that infiltrate the bone marrow (BM).

-induced granulocytic myeloid-derived suppressor cells are protective against polymicrobial sepsis.

Polymicrobial intra-abdominal infections are serious clinical infections that can lead to life-threatening sepsis, which is difficult to treat in part due to the complex and dynamic inflammatory responses involved. Our prior studies demonstrated that immunization with low-virulence species can provide strong protection against lethal polymicrobial sepsis challenge in mice. This long-lived protection was found to be mediated by trained Gr-1 polymorphonuclear leukocytes with features resembling myeloid-derived suppressor cells (MDSCs).

Effect of MMR Vaccination to Mitigate Severe Sequelae Associated With COVID-19: Challenges and Lessons Learned.

Mortality in COVID-19 cases was strongly associated with progressive lung inflammation and eventual sepsis. There is mounting evidence that live attenuated vaccines commonly administered during childhood, also provide beneficial non-specific immune effects, including reduced mortality and hospitalization due to unrelated infections. It has been proposed that live attenuated vaccine-associated non-specific effects are a result of inducing trained innate immunity to function more effectively against broader infections.

Efficacy of and Fungal β-Glucans in Inducing Trained Innate Immune Protection Against Inducers of Sepsis.

Fungal-bacterial intra-abdominal infections (IAI) can lead to sepsis with significant morbidity and mortality. We have established a murine model of () and () IAI that results in acute lethal sepsis. Prior intraperitoneal or intravenous inoculation with low virulence confers high level protection against lethal IAI and sepsis.

Trained Innate Immunity Induced by Vaccination with Low-Virulence Species Mediates Protection against Several Forms of Fungal Sepsis via Ly6G Gr-1 Leukocytes.

We recently discovered a novel form of trained innate immunity (TII) induced by low-virulence species (i.e., Candida dubliniensis) that protects against lethal fungal/bacterial infection.

A Contemporary Warming/Restraining Device for Efficient Tail Vein Injections in a Murine Fungal Sepsis Model.

In rodent models, tail vein injections are important methods for intravenous administration of experimental agents. Tail vein injections typically involve warming of the animal to promote vasodilation, which aids in both the identification of the blood vessels and positioning of the needle into the vessel lumen while securely restraining the animal. Although tail vein injections are common procedures in many protocols and are not considered highly technical if performed correctly, accurate and consistent injections are crucial to obtain reproducible results and minimize variability.

Analysis of Measles-Mumps-Rubella (MMR) Titers of Recovered COVID-19 Patients.

The measles-mumps-rubella (MMR) vaccine has been theorized to provide protection against coronavirus disease 2019 (COVID-19). Our aim was to determine whether any MMR IgG titers are inversely correlated with severity in recovered COVID-19 patients previously vaccinated with MMR II. We divided 80 subjects into two groups, comparing MMR titers to recent COVID-19 severity levels.

Could an Unrelated Live Attenuated Vaccine Serve as a Preventive Measure To Dampen Septic Inflammation Associated with COVID-19 Infection?

We propose the concept that administration of an unrelated live attenuated vaccine, such as MMR (measles, mumps, rubella), could serve as a preventive measure against the worst sequelae of coronavirus disease 2019 (COVID-19). There is mounting evidence that live attenuated vaccines provide nonspecific protection against lethal infections unrelated to the target pathogen of the vaccine by inducing "trained" nonspecific innate immune cells for improved host responses against subsequent infections. Mortality in COVID-19 cases is strongly associated with progressive lung inflammation and eventual sepsis.

Applying the Host-Microbe Damage Response Framework to Pathogenesis: Current and Prospective Strategies to Reduce Damage.

Disease is a complex outcome that can occur as a result of pathogen-mediated damage, host-mediated damage or both. This has led to the revolutionary concept of the damage response framework (DRF) that defines microbial virulence as a function of host immunity. The DRF outlines six scenarios (classes) of host damage or beneficial outcomes, depending on the microbe and the strength of the immune response.

Candida albicans Impacts Staphylococcus aureus Alpha-Toxin Production via Extracellular Alkalinization.

and are common causes of nosocomial infections with severe morbidity and mortality. Murine polymicrobial intra-abdominal infection (IAI) with and results in acute mortality dependent on the secreted cytolytic effector alpha-toxin. Here, we confirmed that alpha-toxin is elevated during polymicrobial growth compared to monomicrobial growth Therefore, this study sought to unravel the mechanism by which drives enhanced staphylococcal alpha-toxin production.

Special Issue: Fungal-Bacterial Interactions-Current Knowledge and Future Perspectives.

We would like to thank all the contributors to the Special Issue on Fungal-Bacterial Interactions-Current Knowledge and Future Perspectives [...

Candida albicans Augments Staphylococcus aureus Virulence by Engaging the Staphylococcal Quorum Sensing System.

and are among the most prevalent nosocomial pathogens that are responsible for severe morbidity and mortality, even with appropriate treatment. Using a murine model of polymicrobial intra-abdominal infection (IAI), we have previously shown that coinfection with these pathogens results in synergistic lethality that is partially dependent on exacerbated prostaglandin signaling, while monomicrobial infection is nonlethal. Therefore, the objective of this study was to identify staphylococcal virulence determinants that drive lethal synergism during polymicrobial IAI.

Spectrum of Trained Innate Immunity Induced by Low-Virulence Species against Lethal Polymicrobial Intra-abdominal Infection.

Polymicrobial intra-abdominal infections (IAI) are clinically prevalent and cause significant morbidity and mortality, especially those involving fungi. Our laboratory developed a mouse model of polymicrobial IAI and demonstrated that coinfection with and (/) results in 80 to 90% mortality in 48 to 72 h due to robust local and systemic inflammation. Surprisingly, inoculation with and resulted in minimal mortality, and rechallenge of mice with lethal / conferred >90% protection up to 60 days postinoculation.

Polymicrobial Intra-Abdominal Infection: Pathogenesis and Perspectives for a Novel Form of Trained Innate Immunity.

Polymicrobial sepsis is difficult to diagnose and treat and causes significant morbidity and mortality, especially when fungi are involved. In vitro, synergism between and various bacterial species has been described for many years. Our laboratory has developed a murine model of polymicrobial intra-abdominal infection with and , demonstrating that polymicrobial infections cause high levels of mortality, while monoinfections do not.

Candida glabrata Has No Enhancing Role in the Pathogenesis of -Associated Denture Stomatitis in a Rat Model.

Denture stomatitis (DS) is a condition characterized by inflammation of the oral mucosa in direct contact with dentures and affects a significant number of otherwise healthy denture wearers. associated DS is predominantly caused by , a dimorphic fungus that readily colonizes and forms biofilms on denture materials. Previous studies showed a requirement for biofilm formation on both palate and dentures in infection and identified fungal morphogenic transcription factors, Efg1 and Bcr1, as key players in DS pathogenesis.

Current patient perspectives of vulvovaginal candidiasis: incidence, symptoms, management and post-treatment outcomes.

Background: Vulvovaginal candidiasis (VVC) is a common infection affecting women worldwide. Reports of patterns/risk factors/trends for episodic/recurrent VVC (RVVC) are largely outdated. The purpose of this study was to obtain current patient perspectives of several aspects of VVC/RVVC.

Identification of Specific Components of the Eicosanoid Biosynthetic and Signaling Pathway Involved in Pathological Inflammation during Intra-abdominal Infection with Candida albicans and Staphylococcus aureus.

Polymicrobial intra-abdominal infections (IAIs) are a significant cause of morbidity and mortality, particularly when fungal pathogens are involved. Our experimental murine model of IAI involving intraperitoneal inoculation of and results in synergistic lethality (∼80%) due to exacerbated inflammation. Monomicrobial infection results in no mortality, despite a microbial burden and dissemination similar to those in a coinfection.

Immune Protection against Lethal Fungal-Bacterial Intra-Abdominal Infections.

Polymicrobial intra-abdominal infections (IAIs) are clinically prevalent and cause significant morbidity and mortality, especially those involving fungi. Our laboratory developed a mouse model of IAI and demonstrated that intraperitoneal inoculation with or other virulent non- (NAC) species plus resulted in 70 to 80% mortality in 48 to 72 h due to robust local and systemic inflammation (sepsis). Surprisingly, inoculation with or with resulted in minimal mortality, and rechallenge of these mice with lethal / (i.

Prostaglandin E Receptor Antagonist with Antimicrobial Activity against Methicillin-Resistant Staphylococcus aureus.

Polymicrobial intra-abdominal infections (IAI) involving and are associated with severe morbidity and mortality (∼80%). Our laboratory discovered that the immunomodulatory eicosanoid prostaglandin E (PGE) plays a key role in the lethal inflammatory response during polymicrobial IAI using a mouse model of infection. In studies designed to uncover key PGE biosynthesis/signaling components involved in the response, selective eicosanoid enzyme inhibitors and receptor antagonists were selected and prescreened for antimicrobial activity against or Unexpectedly, we found that the EP receptor antagonist L-161,982 had direct growth-inhibitory effects on at the physiological concentration required to block the PGE interaction with EP This antimicrobial activity was observed with methicillin-sensitive and methicillin-resistant (MRSA) strains, with the MIC and minimum bactericidal concentration values for planktonic cells being 50 μg/ml and 100 μg/ml, respectively.

Novel Mechanism behind the Immunopathogenesis of Vulvovaginal Candidiasis: "Neutrophil Anergy".

For over 3 decades, investigators have studied the pathogenesis of vulvovaginal candidiasis (VVC) and recurrent VVC (RVVC) through clinical studies and animal models. While there was considerable consensus that susceptibility was not associated with any apparent deficiencies in adaptive immunity, protective immune mechanisms and the role of innate immunity remained elusive. It was not until an innovative live-challenge design was conducted in women that a fuller understanding of the natural history of infection/disease was achieved.