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Frontiers in Cellular and Infection... 2023-mediated vulvovaginal candidiasis (VVC) is a significant challenge in clinical settings, owing to the inefficacy of current antifungals in modulating virulence,... (Review)
Review
-mediated vulvovaginal candidiasis (VVC) is a significant challenge in clinical settings, owing to the inefficacy of current antifungals in modulating virulence, development of resistance, and poor penetration into the biofilm matrix. Various predisposition factors are molecular drivers that lead to the dysbiosis of normal microflora of the vagina, upregulation of central metabolic pathways, morphogenesis, hyphal extension, adhesion, invasion, and biofilm formation leading to chronic infection and recurrence. Hence, it is crucial to understand the molecular mechanism behind the virulence pathways driven by those drivers to decode the drug targets. Finding innovative solutions targeting fungal virulence/biofilm may potentiate the antifungals at low concentrations without affecting the recurrence of resistance. With this background, the present review details the critical molecular drivers and associated network of virulence pathways, possible drug targets, target-specific inhibitors, and probable mode of drug delivery to cross the preclinical phase by appropriate models.
Topics: Female; Humans; Candidiasis, Vulvovaginal; Candida albicans; Antifungal Agents; Vagina; Virulence
PubMed: 37900321
DOI: 10.3389/fcimb.2023.1245808 -
Microbiota Transplant and Gynecological Disorders: The Bridge between Present and Future Treatments.Microorganisms Sep 2023Fecal microbiota transplantation (FMT) is a procedure that involves transferring fecal bacteria from a healthy donor to a patients' intestines to restore gut-immunity... (Review)
Review
Fecal microbiota transplantation (FMT) is a procedure that involves transferring fecal bacteria from a healthy donor to a patients' intestines to restore gut-immunity homeostasis. While FMT was primarily supposed to treat gastrointestinal disorders such as inflammatory bowel disease and irritable bowel syndrome-and especially Clostridium difficile infection (currently the only used as clinical treatment)-recent research has suggested that it may also become a potential treatment for gynecological disorders, including endometriosis and polycystic ovary syndrome (PCOS). On the contrary, vaginal microbiota transplantation (VMT) is a newer and less commonly used procedure than the FMT approach, and its potential applications are still being explored. It involves direct grafting of the entire vaginal microbiota of healthy women into the vaginal tract of patients to easily rebuild the local microbiota environment, restoring vaginal eubiosis and relieving symptoms. Like FMT, VMT is thought to have potential in treating different microbiota-related conditions. In fact, many gynecological disorders, such as bacterial vaginosis and vulvovaginal candidiasis, are thought to be caused by an imbalance in the vaginal microbiota. In this review, we will summarize the development, current challenges, and future perspectives of microbiota transplant, with the aim of exploring new strategies for its employment as a promising avenue for treating a broad range of gynecological diseases.
PubMed: 37894065
DOI: 10.3390/microorganisms11102407 -
Gels (Basel, Switzerland) Sep 2023Fungal infections are caused by opportunistic pathogens that can be life threatening or debilitating. spp. are becoming increasingly resistant to current clinically...
Fungal infections are caused by opportunistic pathogens that can be life threatening or debilitating. spp. are becoming increasingly resistant to current clinically approved antifungal therapeutics. infections afflict not only immunosuppressed but also immunocompetent individuals. Recurrent vulvovaginal candidiasis (RVVC) is a disease that afflicts 5-9% of women. Occidiofungin is a novel cyclic peptide that has a broad spectrum of antifungal activity with a novel fungicidal mechanism of action. A gel formulation containing occidiofungin (OCF001) is being developed for use to treat vulvovaginal candidiasis. The formulated gel for intravaginal application used hydroxyethyl cellulose as the primary gelling agent and hydroxypropyl β-cyclodextrin as a solubilizing agent for occidiofungin. Franz cells and LC-MS/MS were used to determine the rate of drug substance diffusion in the gel formulation. The formulation was tested in an ex vivo mouse skin efficacy study, and the safety was tested following repeat intravaginal administration in rabbits. In this study, the gel formulation was shown to reduce the drug substance rate of diffusion across a skin memetic membrane. The study showed that the formulation extends exposure time to inhibitory concentrations of occidiofungin over a 24-h period and supports a single daily application for the treatment of RVVC.
PubMed: 37888361
DOI: 10.3390/gels9100787 -
Advanced Science (Weinheim,... Dec 2023Candida albicans (C. albicans), a ubiquitous polymorphic fungus in humans, causes different types of candidiasis, including oral candidiasis (OC) and vulvovaginal...
Candida albicans (C. albicans), a ubiquitous polymorphic fungus in humans, causes different types of candidiasis, including oral candidiasis (OC) and vulvovaginal candidiasis (VVC), which are physically and mentally concerning and financially costly. Thus, developing alternative antifungals that prevent drug resistance and induce immunity to eliminate Candida biofilms is crucial. Herein, a novel membrane-targeted aggregation-induced emission (AIE) photosensitizer (PS), TBTCP-QY, is developed for highly efficient photodynamic therapy (PDT) of candidiasis. TBTCP-QY has a high molar absorption coefficient and an excellent ability to generate O and •OH, entering the interior of biofilms due to its high permeability. Furthermore, TBTCP-QY can efficiently inhibit biofilm formation by suppressing the expression of genes related to the adhesion (ALS3, EAP1, and HWP1), invasion (SAP1 and SAP2), and drug resistance (MDR1) of C. albicans, which is also advantageous for eliminating potential fungal resistance to treat clinical infectious diseases. TBTCP-QY-mediated PDT efficiently targets OC and VVC in vivo in a mouse model, induces immune response, relieves inflammation, and accelerates the healing of mucosal defects to combat infections caused by clinically isolated fluconazole-resistant strains. Moreover, TBTCP-QY demonstrates excellent biocompatibility, suggesting its potential applications in the clinical treatment of OC and VVC.
Topics: Mice; Humans; Female; Animals; Photosensitizing Agents; Antifungal Agents; Candidiasis; Candidiasis, Vulvovaginal; Candida albicans; Drug Resistance; Immunity
PubMed: 37875397
DOI: 10.1002/advs.202207736 -
Patient Education and Counseling Jan 2024This systematic review aims to identify what is known about patient and healthcare professional experiences of managing recurrent vulvovaginal thrush by synthesising... (Review)
Review
OBJECTIVE
This systematic review aims to identify what is known about patient and healthcare professional experiences of managing recurrent vulvovaginal thrush by synthesising published findings.
METHODS
Five databases were searched for studies on patient and healthcare professional experiences managing recurrent thrush. Two reviewers independently screened and quality assessed qualitative, quantitative, and mixed-methods studies. Findings from eligible studies were thematically synthesised.
RESULTS
720 papers were identified, and 29 were included. Four descriptive themes were developed to depict the repeated management of recurrent thrush. These themes were: (re)experiencing impacts, (re)identifying recurrent thrush, (re)considering consultations, and (re)trying treatments. An analytic high-order frame of 'interwoven and reoccurring uncertainties' was used to understand these themes.
CONCLUSIONS
Patients and healthcare providers face uncertainties when managing recurrent thrush. The inconsistencies raised across papers suggests an unaddressed gap in knowledge about patient experiences and their informational and support needs; this includes insights about this condition's diagnosis, management, treatment, impacts, and meaning.
PRACTICE IMPLICATIONS
This review has implications for patient education, health promotion, and communication between patients and providers. Our interpretations suggest the need for more research and resources to help support patients and clinicians in managing this condition to promote more understanding, communication, and collaborative care.
Topics: Humans; Health Personnel; Communication; Delivery of Health Care; Qualitative Research
PubMed: 37826917
DOI: 10.1016/j.pec.2023.108004 -
Microbes and Infection 2024Pregnant women with vulvovaginal candidiasis (VVC) may experience adverse pregnancy outcomes such as premature delivery, intrauterine infection, abortion, and neonatal...
Pregnant women with vulvovaginal candidiasis (VVC) may experience adverse pregnancy outcomes such as premature delivery, intrauterine infection, abortion, and neonatal infection. Therefore, finding new treatments for VVC in pregnancy is a public health priority. We aimed to study the adverse consequences of Candida albicans (C. albicans) vaginal infection in pregnant mice and explore the mechanisms by which C. albicans affects macrophages. Our findings contribute to the development of new approaches to treat VVC during pregnancy. We established an animal model of vaginal infection by C. albicans in pregnant mice and observed adverse pregnancy outcomes such as decreased body weight, reduced implantation number, and increased abortion rates. Additionally, we infected mouse macrophage line RAW264.7 cells with C. albicans and established a cell model. We employed RT-qPCR, Western blot, and immunofluorescence staining to verify the changes in the IL-15/STAT5 signaling pathway and the role it played on the M1 polarization of C. albicans-infected macrophages at both the gene and protein levels. Our results indicate that the adverse pregnancy outcomes in VVC may be linked to changes in the IL-15/STAT5 pathway induced by C. albicans, which could impact macrophage M1 polarization.
Topics: Animals; Female; Humans; Mice; Pregnancy; Antifungal Agents; Candida albicans; Candidiasis, Vulvovaginal; Interleukin-15; Macrophages; Placenta; Pregnancy Outcome; Signal Transduction; STAT5 Transcription Factor
PubMed: 37802467
DOI: 10.1016/j.micinf.2023.105232 -
Current Medical Mycology Dec 2022Fungal infection by species of pathogenic with antifungal resistance is currently a serious problem. Treatment with new medications is becoming more challenging to...
BACKGROUND AND PURPOSE
Fungal infection by species of pathogenic with antifungal resistance is currently a serious problem. Treatment with new medications is becoming more challenging to manage this type of infection. The present study aimed to investigate the antifungal effect of essential oils (EOs) against itraconazole-resistant species of pathogenic .
MATERIALS AND METHODS
Seven essential oils were tested on 15 clinical isolates of itraconazole-resistant from patients with vulvovaginal candidiasis. The antifungal action of selected EOs was evaluated using the disc diffusion method with the determination of the minimum inhibitory concentration (MIC) of effective Eos.
RESULTS
Radish EO was the most effective type against all isolates with MICs between 3.125% and 6.25% (v/v) .It also had a stronger effect than itraconazole. Six other EOs showed antifungal effects at varying concentrations and were dependent upon the type of isolate. Low concentrations of these six EOs were more effective against many isolates than their high concentrations. Moreover, camphor and linseed EOs were less effective on isolates.
CONCLUSION
Radish EO has a strong antifungal activity against itraconazole-resistance species of , even more than itraconazole. The antifungal action of some EOs can be increased through the use of low concentrations.
PubMed: 37736607
DOI: 10.32598/CMM.2023.1359 -
Current Medical Mycology Dec 2022Genotyping of pathogenic microorganisms is important for epidemiological studies and the adoption of appropriate strategies to control infectious diseases. In this...
BACKGROUND AND PURPOSE
Genotyping of pathogenic microorganisms is important for epidemiological studies and the adoption of appropriate strategies to control infectious diseases. In this regard, the present study aimed to genotype strains isolated from vulvovaginal candidiasis (VVC) patients using combined ABC type (25SrDNA) and repetitive sequence (RPS) typing systems. using combined typing systems of ABC type (25SrDNA) and repetitive sequence (RPS).
MATERIALS AND METHODS
In total, 140 patients with VVC were investigated. Vaginal discharges were collected on Sabouraud dextrose agar and identified by CHROMagar. After species identification, a polymerase chain reaction system targeting 25S rDNA as well as ALT repeats in the RPS was designed to determine genotypes. The dendrogram was constructed by zero-one matrix data based on the combination of ABC and RPS typing systems. Statistical analysis of data was performed in SPSS software (version 23).
RESULTS
In total, 41 (29.3%) isolates were obtained from 140 VVC patients. The most common species that were identified included (56.1%) and (39%). Genotype A3 with five isolates (31.25%) had the highest frequency, followed by B2/3 with three isolates (18.3%), A3/4, C3/4, and B3/4 with two isolates (12.5%), and C2/3 and C3 with one isolate (6.25%), respectively. No significant association was found between the genotypes and antifungal resistance (<0.05).
CONCLUSION
The results showed that non- species are more prevalent in VVC patients, compared to . The results also indicated that ABC and RPS typings are useful for rapid genotyping and differentiation of isolates in regional and small-scale studies.
PubMed: 37736604
DOI: 10.32598/CMM.2023.1364 -
Microbes and Infection 2024The Candida albicans population displays high genetic diversity illustrated by 18-well differentiated genetic clusters. Cluster 13, also known as Candida africana, is an...
The Candida albicans population displays high genetic diversity illustrated by 18-well differentiated genetic clusters. Cluster 13, also known as Candida africana, is an outlying cluster and includes strains first described as atypical C. albicans isolates of vaginal origin, showing apparent tropism for the female genital tract. In our study, we combined in vitro, and in vivo models to explore the colonization and pathogenic potential of C. africana. We report that C. africana has similar fitness to C. albicans when it comes to colonization of the oral and vaginal mucosa, however it has decreased fitness in gastro-intestinal colonization and systemic infection. Interestingly, despite high population homogeneity, our in vitro data highlighted for the first time a variability in terms of growth rate, biofilm formation and filamentation properties between C. africana strains. Overall, our data lays the foundations for exploring specific features of C. africana that might contribute to its apparent niche restriction.
Topics: Female; Humans; Candidiasis, Vulvovaginal; Antifungal Agents; Candida; Candida albicans
PubMed: 37734535
DOI: 10.1016/j.micinf.2023.105230 -
Biomedica : Revista Del Instituto... Aug 2022Proteases and phospholipases are virulence factors of Candida spp. that play an important role in tissue invasion. Among the factors related to the host some are...
INTRODUCTION
Proteases and phospholipases are virulence factors of Candida spp. that play an important role in tissue invasion. Among the factors related to the host some are associated with environmental characteristics and others with Candida colonization.
OBJECTIVES
To determine phospholipase and protease activities in colonizing and pathogenic strains, isolated from pregnant women in Cartagena de Indias.
MATERIALS AND METHODS
Phospholipase and protease activity was determined in 56 isolates, evaluating substrate degradation and calculating the enzyme activity coefficient. Phospholipase and protease activities were compared between colonizing and pathogenic strains.
RESULTS
“Very high” (<0.69) phospholipase and protease activity was found in 34 and 14 isolates, respectively. There was no significant difference when comparing phospholipase and protease activities between colonizing and pathogenic isolates.
CONCLUSIONS
Phospholipase activity predominated as a virulence factor in the studied strains, but no significant difference found between colonizing and pathogenic strains for phospholipase and protease activities.
Topics: Female; Humans; Candida; Vulvovaginitis
PubMed: 37721921
DOI: 10.7705/biomedica.6759