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Current Research in Microbial Sciences 2024Ibrexafungerp (IBX) is a new antifungal drug that recently entered the antifungal landscape. It disrupts fungal cell wall synthesis by non-competitive inhibition of the... (Review)
Review
Ibrexafungerp (IBX) is a new antifungal drug that recently entered the antifungal landscape. It disrupts fungal cell wall synthesis by non-competitive inhibition of the β-(1,3)-D-glucan (BDG) synthase enzyme. It has demonstrated activity against a range of pathogens including and spp., as well as retaining its activity against azole-resistant and echinocandin-resistant strains. It also exhibits anti-biofilm properties. Pharmacokinetic (PK) studies revealed favorable bioavailability, high protein binding, and extensive tissue distribution with a low potential for CYP-mediated drug interactions. It is characterized by the same mechanism of action of echinocandins with limited cross-resistance with other antifungal agents. Resistance to this drug can arise from mutations in the genes, primarily mutations in . In vivo, IBX was found to be effective in murine models of invasive candidiasis (IC) and invasive pulmonary aspergillosis (IPA). It also showed promising results in preventing and treating infections. Clinical trials showed that IBX was effective and non-inferior to fluconazole in treating vulvovaginal candidiasis (VVC), including complicated cases, as well as in preventing its recurrence. These trials positioned it as a Food and Drug Administration (FDA)-approved option for the treatment and prophylaxis of VVC. Trials showed comparable responses to standard-of-care in IC, with favorable preliminary results in infections in terms of efficacy and tolerability as well as in refractory cases of IC. Mild adverse reactions have been reported including gastrointestinal symptoms. Overall, IBX represents a significant addition to the antifungal armamentarium, with its unique action, spectrum of activity, and encouraging clinical trial results warranting further investigation.
PubMed: 38873590
DOI: 10.1016/j.crmicr.2024.100245 -
Frontiers in Microbiology 2024Vaginitis is a common infection in women, with approximately 75% of women experiencing at least one episode during their lifetime. Although antimicrobial agents are...
BACKGROUND
Vaginitis is a common infection in women, with approximately 75% of women experiencing at least one episode during their lifetime. Although antimicrobial agents are widely used to treat vaginitis, recurrent vaginitis occurs in some patients. Resistance to these agents is the major cause of recurrent vaginitis. Therefore, there is an urgent need to develop novel drugs.
METHODS
We investigated the efficacy of a new biological bacteriostatic agent (BBA), composed of lysozyme, phytoalexin, chitosan oligosaccharide, sinensetin, 18β/20α-glycyrrhizin, and betaine, against vaginitis using and studies. First, we evaluated the antibacterial effects of BBA against 13 microbial strains commonly present in aerobic vaginitis, bacterial vaginosis, vulvovaginal candidiasis, and healthy vaginas. Second, we assessed the safety of various doses of BBA administered orally for 4 weeks in female mice. Third, we examined the anti-proliferative and anti-inflammatory effects of BBA in , -, and -induced vaginitis models. Finally, we evaluated the anti-vaginitis effect of a BBA gel prepared with 0.5% (w/v) ammonium acryloyldimethyltaurate/Vp copolymer.
RESULTS
BBA effectively suppressed the growth of the main causative pathogens of vaginitis . BBA, either undiluted or diluted two-fold, inhibited all microorganisms cultured for 8 h. No obvious organ damage was detected when BBA was administered to mice. Both BBA alone and 70% BBA in a gel formulation effectively inhibited the proliferation of , , and in vaginal lavage samples and alleviated tissue inflammation in mice with vaginitis. The 70% BBA gel performed better than BBA alone at treating vaginitis in mice infected with .
CONCLUSION
BBA alone and a 70% BBA gel inhibited the growth of pathogens and effectively alleviated inflammation caused by , , and .
PubMed: 38860217
DOI: 10.3389/fmicb.2024.1341878 -
Frontiers in Global Women's Health 2024Vaginal colonization (CC) can lead to vulvovaginal candidiasis, the second most prevalent vaginal condition worldwide, and has been associated with adverse birth...
Second trimester vaginal colonization among pregnant women attending antenatal care in Bukavu, Democratic Republic of the Congo: prevalence, clinical correlates, risk factors and pregnancy outcomes.
INTRODUCTION
Vaginal colonization (CC) can lead to vulvovaginal candidiasis, the second most prevalent vaginal condition worldwide, and has been associated with adverse birth outcomes. However, no data on CC in the Democratic Republic of the Congo are available. We investigated the prevalence, species, clinical correlates, risk factors and pregnancy outcomes in women with CC in the second trimester of pregnancy.
MATERIAL AND METHODS
In Bukavu, the Democratic Republic of the Congo, pregnant women were recruited during antenatal care between 16 and 20 weeks of gestation from January 2017 to October 2017 and followed until delivery. Sociodemographics, sexual behavioral, hygienic and clinical characteristics, microbiological data and pregnancy outcomes were collected. detection and speciation was performed with microscopy (Gram-stained smears and wet-mount) and/or quantitative PCR. Multivariate regression models were used to estimate the different associations with CC.
RESULTS
The prevalence of CC by wet mount, microscopy of Gram-stain smears and qPCR was 27.9%, 28.1% and 38.2%, respectively. was the most prevalent species (91.0%). Previous genital infections, an intermediate vaginal microbiota, bacterial vaginosis, and the use of pit toilets were risk factors for CC. Clinically, CC was associated with itching only. Women with CC had twice the odds for preterm birth, if concentration was high, the odds were four times higher.
CONCLUSIONS
In Bukavu, the Democratic Republic of the Congo, the prevalence of CC was high and associated with microbiological and modifiable risk factors. Screening and treatment for CC during antenatal care should be investigated as a possible strategy to reduce preterm birth.
PubMed: 38847001
DOI: 10.3389/fgwh.2024.1339821 -
International Journal of Nanomedicine 2024Due to its prevalence, recurrence, and the emergence of drug-resistance, vaginitis significantly impacts the well-being of women. Although cinnamon essential oil (CEO)...
BACKGROUND
Due to its prevalence, recurrence, and the emergence of drug-resistance, vaginitis significantly impacts the well-being of women. Although cinnamon essential oil (CEO) possesses antifungal activity, its hydrophobic properties limit its clinical application.
PURPOSE
To overcome this challenge, a nanoemulsification technology was employed to prepare cinnamon essential oil-nanoemulsion (CEO@NE), and its therapeutic efficacy and action mechanism for vaginitis was investigated in vivo and in vitro.
MATERIALS AND METHODS
CEO@NE, composed of 4% CEO, 78% distilled water, and 18% Tween 80, was prepared by ultrasonic nanoemulsification. The physical properties, anti- activity, cytotoxicity, immunomodulatory potential and storage stability of CEO@NE were explored. Subsequently, the effect of intravaginal CEO@NE treatment on vaginitis was investigated in mice. To comprehend the possible mechanism of CEO@NE, an analysis was conducted to ascertain the production of intracellular reactive oxygen species (ROS) in .
RESULTS
CEO@NE, with the droplet size less than 100 nm and robust storage stability for up to 8 weeks, exhibited comparable anti- activity with CEO. CEO@NE at the concentration lower than 400 μg/mL had no cytotoxic and immunomodulatory effects on murine splenocytes. Intravaginal treatment of CEO@NE (400 μg/mL, 20 μL/day/mouse for 5 consecutive days) curbed colonization, ameliorated histopathological changes, and suppressed inflammatory cytokine production in mice intravaginally challenged with . Notably, this treatment preserved the density of vaginal lactic acid bacteria (LAB) crucial for vaginal health. Co-culturing with CEO@NE revealed concentration-dependent augmentation of intracellular ROS generation and ensuing cell death. In addition, co-culturing LPS-stimulated murine splenocytes with CEO@NE yielded a decrease in the generation of cytokines.
CONCLUSION
This discovery provides insight into the conceivable antifungal and anti-inflammatory mechanisms of CEO@NE to tackle vaginitis. CEO@NE offers a promising avenue to address the limitations of current treatments, providing novel strategy for treating vaginitis.
Topics: Female; Animals; Oils, Volatile; Candidiasis, Vulvovaginal; Candida albicans; Antifungal Agents; Mice; Administration, Intravaginal; Cinnamomum zeylanicum; Emulsions; Reactive Oxygen Species; Humans; Nanoparticles; Mice, Inbred BALB C
PubMed: 38828194
DOI: 10.2147/IJN.S458593 -
BioRxiv : the Preprint Server For... May 2024Candidalysin is a cytolytic peptide produced by the opportunistic fungal pathogen This peptide is a key virulence factor in mouse models of mucosal and hematogenously...
Candidalysin is a cytolytic peptide produced by the opportunistic fungal pathogen This peptide is a key virulence factor in mouse models of mucosal and hematogenously disseminated candidiasis. Despite intense interest in the role of candidalysin in pathogenicity, its host cell targets have remained elusive. To fill this knowledge gap, we performed a genome-wide loss-of-function CRISPR screen in a human oral epithelial cell line to identify specific host factors required for susceptibility to candidalysin-induced cellular damage. Among the top hits were , and , genes that function in glycosaminoglycan (GAG) biosynthesis. Deletion of these genes led to the absence of GAGs such as heparan sulfate on the epithelial cell surface and increased resistance to damage induced by both candidalysin and live Biophysical analyses including surface plasmon resonance and atomic force and electron microscopy indicated that candidalysin physically binds to sulfated GAGs, facilitating its oligomerization or enrichment on the host cell surface. The addition of exogenous sulfated GAGs or the GAG analogue dextran sulfate protected cells against candidalysin-induced damage. Dextran sulfate, but not non-sulfated dextran, also inhibited epithelial cell endocytosis of and fungal-induced epithelial cell cytokine and chemokine production. In a murine model of vulvovaginal candidiasis, topical dextran sulfate administration reduced host tissue damage and decreased intravaginal IL-1β and neutrophil levels. Collectively, these data indicate that GAGs are epithelial cell targets of candidalysin and can be used therapeutically to protect cells from candidalysin-induced damage.
PubMed: 38826446
DOI: 10.1101/2024.05.23.595417 -
Pharmaceuticals (Basel, Switzerland) May 2024The Pulsatilla decoction is a well-known herbal remedy used in clinical settings for treating vulvovaginal candidiasis (VVC). However, the specific mechanism that makes...
Transcriptomics Reveals Effect of Decoction Butanol Extract in Alleviating Vulvovaginal Candidiasis by Inhibiting Neutrophil Chemotaxis and Activation via TLR4 Signaling.
The Pulsatilla decoction is a well-known herbal remedy used in clinical settings for treating vulvovaginal candidiasis (VVC). However, the specific mechanism that makes it effective is still unclear. Recent studies have shown that in cases of VVC, neutrophils recruited to the vagina, influenced by heparan sulfate (HS), do not successfully engulf (). Instead, they release many inflammatory factors that cause damage to the vaginal mucosa. This study aims to understand the molecular mechanism by which the n-butanol extract of Pulsatilla decoction (BEPD) treats VVC through transcriptomics. High-performance liquid chromatography was used to identify the primary active components of BEPD. A VVC mouse model was induced using an estrogen-dependent method and the mice were treated daily with BEPD (20 mg/kg, 40 mg/kg, and 80 mg/kg) for seven days. The vaginal lavage fluid of the mice was analyzed for various experimental indices, including fungal morphology, fungal burden, degree of neutrophil infiltration, and cytokines. Various assessments were then performed on mouse vaginal tissues, including pathological assessment, immunohistochemistry, immunofluorescence, Western blot (WB), quantitative real-time PCR, and transcriptome assays. Our results showed that BEPD reduced vaginal redness and swelling, decreased white discharge, inhibited hyphae formation, reduced neutrophil infiltration and fungal burden, and attenuated vaginal tissue damage compared with the VVC model group. The high-dose BEPD group even restored the damaged vaginal tissue to normal levels. The medium- and high-dose groups of BEPD also significantly reduced the levels of IL-1β, IL-6, TNF-α, and LDH. Additionally, transcriptomic results showed that BEPD regulated several chemokine (CXCL1, CXCL3, and CXCL5) and S100 alarmin (S100A8 and S100A9) genes, suggesting that BEPD may treat VVC by affecting chemokine- and alarmin-mediated neutrophil chemotaxis. Finally, we verified that BEPD protects the vaginal mucosa of VVC mice by inhibiting neutrophil recruitment and chemotaxis in an animal model of VVC via the TLR4/MyD88/NF-κB pathway. This study provides further evidence to elucidate the mechanism of BEPD treatment of VVC.
PubMed: 38794163
DOI: 10.3390/ph17050594 -
Tropical Medicine and Infectious Disease May 2024Vulvovaginal candidiasis (VVC) is a common condition that can lead to significant discomfort, affecting approximately 70-75% of women at least once in their lives.... (Review)
Review
Vulvovaginal candidiasis (VVC) is a common condition that can lead to significant discomfort, affecting approximately 70-75% of women at least once in their lives. During pregnancy, the prevalence of VVC is estimated to be around 20%, peaking at about 30% in the third trimester, with a number of specific risk factors predisposing to yeast infection being identified and needing elucidation. This review aims to provide updated knowledge on candidiasis during pregnancy, addressing risk factors and maternal and neonatal outcomes, as well as discussing optimal therapeutic strategies to safeguard mothers and newborns. The bibliographic search involved two biomedical databases, PubMed and Embase, without imposing time limits. Among all spp., remains the most frequent causative species. The hyperestrogenic environment of the vaginal mucosa and reduced immune defenses, physiological effects of pregnancy, create conditions favorable for spp. vaginal colonization and hence VVC. Recent evidence shows an association between VVC and adverse obstetric outcomes, including premature membrane rupture (PROM), chorioamnionitis, preterm birth, and puerperal infections. Prompt and effective management of this condition is therefore crucial to prevent adverse obstetric outcomes, maternal-fetal transmission, and neonatal disease. Additional studies are required to confirm the benefits of systemic treatment for maternal candida infection or colonization in preventing premature birth or neonatal systemic candidiasis.
PubMed: 38787047
DOI: 10.3390/tropicalmed9050114 -
Journal of Fungi (Basel, Switzerland) May 2024The United Arab Emirates has very little data on the incidence or prevalence of fungal diseases. Using total and underlying disease risk populations and likely affected...
The United Arab Emirates has very little data on the incidence or prevalence of fungal diseases. Using total and underlying disease risk populations and likely affected proportions, we have modelled the burden of fungal disease for the first time. The most prevalent serious fungal conditions are recurrent vulvovaginitis (~190,000 affected) and fungal asthma (~34,000 affected). Given the UAE's low prevalence of HIV, we estimate an at-risk population of 204 with respect to serious fungal infections with cryptococcal meningitis estimated at 2 cases annually, 15 cases of pneumonia (PCP) annually, and 20 cases of esophageal candidiasis in the HIV population. PCP incidence in non-HIV patients is estimated at 150 cases annually. Likewise, with the same low prevalence of tuberculosis in the country, we estimate a total chronic pulmonary aspergillosis prevalence of 1002 cases. The estimated annual incidence of invasive aspergillosis is 505 patients, based on local data on rates of malignancy, solid organ transplantation, and chronic obstructive pulmonary disease (5.9 per 100,000). Based on the 2022 annual report of the UAE's national surveillance database, candidaemia annual incidence is 1090 (11.8/100,000), of which 49.2% occurs in intensive care. Fungal diseases affect ~228,695 (2.46%) of the population in the UAE.
PubMed: 38786708
DOI: 10.3390/jof10050353 -
Ethiopian Journal of Health Sciences Sep 2023Vulvovaginal candidiasis is one of the most common vaginal infections worldwide. We conducted this systematic review and meta-analysis to determine the effect of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Vulvovaginal candidiasis is one of the most common vaginal infections worldwide. We conducted this systematic review and meta-analysis to determine the effect of probiotics in the treatment of vulvovaginal candidiasis.
METHODS
A comprehensive search of databases including PubMed, Scopus, Cochrane, Scientific Information Database (SID), IranMedex, and Google Scholar search engine was performed. The search was conducted from inception to 1 October 2022, to identify published English or Persian language randomized control trials (RCTs) of women with vulvovaginal candidiasis who received probiotics as medical treatment. The quality of the included studies was assessed using the Oxford Center for Evidence Based Medicine checklist All statistical analyses were performed using Comprehensive Meta-analysis (CMA) version 2.
RESULTS
Six RCTs were included in this review. The results showed that treatment with probiotic was not different from placebo regarding the rate of positive culture (OR: 1.12; 95% CI: 0.390 to 3.26, P=0.825); treatment with probiotic was more effective compared to placebo regarding the rate of recurrence. (OR: 0.14; P= 0.01; 95 % CI: 0.028-0.7).
CONCLUSION
Probiotics have a beneficial effect in the treatment of women with vulvovaginal candidiasis. Our results provide evidence for an alternative treatment modality for vaginal candidiasis using probiotics.
Topics: Candidiasis, Vulvovaginal; Probiotics; Humans; Female; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 38784519
DOI: 10.4314/ejhs.v33i5.18 -
PloS One 2024Candida albicans (C. albicans) can behave as a commensal yeast colonizing the vaginal mucosa, and in this condition is tolerated by the epithelium. When the epithelial...
Candida albicans (C. albicans) can behave as a commensal yeast colonizing the vaginal mucosa, and in this condition is tolerated by the epithelium. When the epithelial tolerance breaks down, due to C. albicans overgrowth and hyphae formation, the generated inflammatory response and cell damage lead to vulvovaginal candidiasis (VVC) symptoms. Here, we focused on the induction of mitochondrial reactive oxygen species (mtROS) in vaginal epithelial cells after C. albicans infection and the involvement of fungal burden, morphogenesis and candidalysin (CL) production in such induction. Bioluminescent (BLI) C. albicans, C. albicans PCA-2 and C. albicans 529L strains were employed in an in vitro infection model including reconstituted vaginal epithelium cells (RVE), produced starting from A-431 cell line. The production of mtROS was kinetically measured by using MitoSOX™ Red probe. The potency of C. albicans to induced cell damage to RVE and C. albicans proliferation have also been evaluated. C. albicans induces a rapid mtROS release from vaginal epithelial cells, in parallel with an increase of the fungal load and hyphal formation. Under the same experimental conditions, the 529L C. albicans strain, known to be defective in CL production, induced a minor mtROS release showing the key role of CL in causing epithelial mithocondrial activation. C. albicans PCA-2, unable to form hyphae, induced comparable but slower mtROS production as compared to BLI C. albicans yeasts. By reducing mtROS through a ROS scavenger, an increased fungal burden was observed during RVE infection but not in fungal cultures grown on abiotic surface. Collectively, we conclude that CL, more than fungal load and hyphae formation, seems to play a key role in the rapid activation of mtROS by epithelial cells and in the induction of cell-damage and that mtROS are key elements in the vaginal epithelial cells response to C. albicans.
Topics: Candida albicans; Female; Humans; Mitochondria; Vagina; Reactive Oxygen Species; Epithelial Cells; Fungal Proteins; Candidiasis, Vulvovaginal; Hyphae; Cell Line
PubMed: 38768097
DOI: 10.1371/journal.pone.0303449