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MSystems Mar 2024Although vaginitis is closely related to vaginal microecology in females, the precise composition and functional potential of different types of vaginitis remain...
UNLABELLED
Although vaginitis is closely related to vaginal microecology in females, the precise composition and functional potential of different types of vaginitis remain unclear. Here, metagenomic sequencing was applied to analyze the vaginal flora in patients with various forms of vaginitis, including cases with a clue cell proportion ranging from 1% to 20% (Clue1_20), bacterial vaginitis (BV), vulvovaginal candidiasis (VVC), and BV combined with VVC (VVC_BV). Our results identified as an important biomarker between BV and Clue1_20. Moreover, a gradual decrease was observed in the relative abundance of shikimic acid metabolism associated with bacteria producing indole as well as a decline in the abundance of in patients with BV, Clue1_20, and healthy women. Interestingly, the vaginal flora of patients in the VVC_BV group exhibited structural similarities to that of the VVC group, and its potentially functional characteristics resembled those of the BV and VVC groups. Finally, was found in high abundance in healthy samples, greatly contributing to the stability of the vaginal environment. For the further study of , we isolated five strains of from healthy samples and evaluated their capacity to inhibit biofilms and produce lactic acid to select the potential probiotic candidate for improving vaginitis in future clinical studies. Overall, we successfully identified bacterial biomarkers of different vaginitis and characterized the dynamic shifts in vaginal flora between patients with BV and healthy females. This research advances our understanding and holds great promise in enhancing clinical approaches for the treatment of vaginitis.
IMPORTANCE
Vaginitis is one of the most common gynecological diseases, mostly caused by infections of pathogens such as and . In recent years, it has been found that the stability of the vaginal flora plays an important role in vaginitis. Furthermore, the abundant -producing rich lactic acid in the vagina provides a healthy acidic environment such as . The metabolites of can inhibit the colonization of pathogens. Here, we collected the vaginal samples of patients with bacterial vaginitis (BV), vulvovaginal candidiasis (VVC), and BV combined with VVC to discover the differences and relationships among the different kinds of vaginitis by metagenomic sequencing. Furthermore, because of the importance of in promoting vaginal health, we isolated multiple strains from vaginal samples of healthy females and chose the most promising strain with potential probiotic benefits to provide clinical implications for treatment strategies.
Topics: Humans; Female; Vaginosis, Bacterial; Candidiasis, Vulvovaginal; Vagina; Gardnerella vaginalis; Lactobacillus; Lactobacillus crispatus; Lactic Acid
PubMed: 38364107
DOI: 10.1128/msystems.01377-23 -
Clinical Infectious Diseases : An... Aug 2015Biofilms are microbial communities of surface-attached cells embedded in a self-produced extracellular matrix. They are of major medical significance because they... (Review)
Review
Biofilms are microbial communities of surface-attached cells embedded in a self-produced extracellular matrix. They are of major medical significance because they decrease susceptibility to antimicrobial agents and enhance the spread of antimicrobial resistance. Biofilm-associated bacterial and fungal microorganisms have increasingly been recognized to play a role in multiple infectious diseases, particularly in their persistence and recurrence. More recently, biofilms have also been implicated in vaginal infections, notably bacterial vaginosis (BV) and vulvovaginal candidiasis (VVC), particularly in the setting of treatment failure and recurrence. The purpose of this review is to discuss the impact of biofilms on the management and treatment of BV and recurrent VVC and highlight the need for additional research and development of novel therapeutics targeting pathogenic vaginal biofilms.
Topics: Animals; Anti-Infective Agents; Biofilms; Candidiasis, Vulvovaginal; Disease Models, Animal; Female; Humans; Recurrence; Treatment Failure; Vaginosis, Bacterial
PubMed: 25935553
DOI: 10.1093/cid/civ353 -
Antimicrobial Agents and Chemotherapy Jun 2023The emergence of azole-resistant and biofilm-forming Candida spp. contributes to the constantly increasing incidence of vulvovaginal candidiasis. It is imperative to...
Newly Discovered Antimicrobial Peptide Scyampcin from Scylla paramamosain Exhibits a Multitargeted Candidacidal Mechanism and Is Effective in a Murine Model of Vaginal Candidiasis.
The emergence of azole-resistant and biofilm-forming Candida spp. contributes to the constantly increasing incidence of vulvovaginal candidiasis. It is imperative to explore new antifungal drugs or potential substituents, such as antimicrobial peptides, to alleviate the serious crisis caused by resistant fungi. In this study, a novel antimicrobial peptide named Scyampcin was identified in the mud crab Scylla paramamosain. Scyampcin exhibited broad-spectrum antimicrobial activity against bacteria and fungi, was particularly effective against planktonic and biofilm cells of Candida albicans, and exhibited no cytotoxicity to mammalian cells (HaCaT and RAW264.7) or mouse erythrocytes. Transcriptomic analysis revealed four potential candidacidal modes of Scyampcin, including promotion of apoptosis and autophagy and inhibition of ergosterol biosynthesis and the cell cycle. Further study showed that Scyampcin caused damage to the plasma membrane and induced apoptosis and cell cycle arrest at G/M in C. albicans. Scanning and transmission electron microscopy demonstrated that Scyampcin-treated C. albicans cells were deformed with vacuolar expansion and destruction of organelles. In addition, C. albicans cells pretreated with the autophagy inhibitor 3-methyladenine significantly delayed the candidacidal effect of Scyampcin, suggesting that Scyampcin might contribute to autophagic cell death. In a murine model of vulvovaginal candidiasis, the fungal burden of vaginal lavage was significantly decreased after treatment with Scyampcin.
Topics: Humans; Female; Mice; Animals; Candidiasis, Vulvovaginal; Antimicrobial Peptides; Disease Models, Animal; Brachyura; Candida albicans; Antifungal Agents; Mammals
PubMed: 37162345
DOI: 10.1128/aac.00022-23 -
Infection and Immunity Mar 2018For over 3 decades, investigators have studied the pathogenesis of vulvovaginal candidiasis (VVC) and recurrent VVC (RVVC) through clinical studies and animal models.... (Review)
Review
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. These studies revealed that symptomatic infection is associated with recruitment of polymorphonuclear neutrophils (PMNs) into the vaginal lumen. Subsequent studies in the established mouse model demonstrated that infiltrating PMNs were incapable of reducing the fungal burden, which supported the hypothesis that VVC/RVVC was an immunopathology, whereby and the host response drive symptomatic disease. Further studies in mice revealed the requirement for hyphae and identified pattern recognition receptors (PRRs) and proinflammatory mediators responsible for the PMN response, all of which are critical pieces of the immunopathogenesis. However, a mechanism explaining PMN dysfunction at the vaginal mucosa remained an enigma. Ultimately, by employing mouse strains resistant or susceptible to chronic VVC, it was determined that heparan sulfate (HS) in the vaginal environment of susceptible mice serves as a competitive ligand for Mac-1 on PMNs, which effectively renders the PMNs incapable of binding to to initiate killing. Hence, the outcome of symptomatic VVC/RVVC is postulated to be dependent on a PMN-mediated immunopathogenic response involving HS that effectively places the neutrophils in a state of functional anergy.
Topics: Animals; Candida albicans; Candidiasis, Vulvovaginal; Female; Humans; Neutrophil Infiltration; Neutrophils; Vagina
PubMed: 29203543
DOI: 10.1128/IAI.00684-17 -
Cleveland Clinic Journal of Medicine Mar 2017Vulvar and vaginal disorders are among the most common problems seen in ambulatory care. The cause is usually infectious, but noninfectious causes should also be... (Review)
Review
Vulvar and vaginal disorders are among the most common problems seen in ambulatory care. The cause is usually infectious, but noninfectious causes should also be considered, and differentiating them can be challenging. Accurate diagnosis based on patient history, physical examination, and laboratory testing is necessary so that effective therapy can be chosen.
Topics: Candidiasis, Vulvovaginal; Diagnosis, Differential; Female; Herpes Genitalis; Humans; Lichen Planus; Symptom Assessment; Trichomonas Vaginitis; Vaginosis, Bacterial; Vulvovaginitis
PubMed: 28322677
DOI: 10.3949/ccjm.84a.15163 -
Mycoses May 2016Vulvovaginal candidosis (VVC) is a common gynaecological disorder that is delineated by the inflammation of vaginal wall and it is caused by the opportunistic fungal... (Review)
Review
Vulvovaginal candidosis (VVC) is a common gynaecological disorder that is delineated by the inflammation of vaginal wall and it is caused by the opportunistic fungal pathogen Candida species. In fact, three out of every four women will experience at least one occasion of VVC during some point in their lives. Although uncomplicated VVC is relatively harmless, the complicated VVC such as recurrent attack often creates restlessness and depression in the patients, thus greatly affects their quality of life. Managements of VVC are usually associated with the use of antimycotic suppositories, topical cream or oral agents. These antimycotic agents are either available over-the-counter or prescribed by the clinicians. In recent decades, the rise of clinical challenges such as the increased prevalence of resistant Candida strains, recurrent VVC infection and adverse effects of multidrug interactions have necessitated the development of novel therapeutic or prophylactic options to combat the complicated VVC in the future. In this review, we discuss the current antimycotic treatments available for Candida vaginitis and the problems that exist in these seemingly effective treatments. Besides, we attempt to contemplate some of the future and prospective strategies surrounding the development of alternative therapeutic and prophylactic options in treating and preventing complicated VVC respectively.
Topics: Administration, Oral; Administration, Topical; Antifungal Agents; Candida; Candidiasis, Vulvovaginal; Drug Interactions; Drug Resistance, Fungal; Female; Humans; Nonprescription Drugs; Pregnancy; Pregnancy Complications, Infectious; Recurrence
PubMed: 26765516
DOI: 10.1111/myc.12455 -
Antimicrobial Agents and Chemotherapy Nov 2019Recurrent vulvovaginal candidiasis (RVVC) is a widespread chronic infection that has a substantial negative impact on work and quality of life. The development of...
Recurrent vulvovaginal candidiasis (RVVC) is a widespread chronic infection that has a substantial negative impact on work and quality of life. The development of antimicrobial resistance and biofilm formation are speculated to contribute to pathogenicity and treatment ineffectiveness. Designed antimicrobial peptides (dAMPs) are chemically modified from endogenous antimicrobial peptides that provide the first line of defense against pathogens. The goal here is to identify a dAMP for the topical treatment of RVVC. The dAMP MICs were determined for 46 fluconazole-susceptible and fluconazole-resistant spp. clinical isolates. The possibility of inducing dAMP drug resistance and comparison of dAMP and fluconazole activity against preformed biofilm and biofilm formation were evaluated. Assessment of mammalian cell viability was determined using bioluminescent human keratinocytes. The dAMP effect on fungus was probed via scanning electron microscopy, and topically applied dAMP activity was evaluated in a rodent vulvovaginal candidiasis (VVC) infection model. dAMPs demonstrated broad-spectrum antimicrobial activity against common causative clinical isolates, reduced preformed biofilm, and inhibited biofilm formation. An evaluated dAMP did not induce resistance after repeated exposure of The dAMPs were selective for cells with limited mammalian cytotoxicity with substantial activity in a rodent VVC model. dAMPs are described as having potent antifungal and antibiofilm activity, likely direct membrane action with selectivity for cells, with limited resistance development. Combined with activity in a rodent VVC model, the data support clinical evaluation of dAMPs for topical treatment of VCC and recurrent VVC infections.
Topics: Animals; Antifungal Agents; Antimicrobial Cationic Peptides; Biofilms; Candida; Candidiasis, Vulvovaginal; Cell Survival; Drug Resistance, Fungal; Female; Fluconazole; Humans; Keratinocytes; Microbial Sensitivity Tests; Peptides; Rats; Rats, Wistar
PubMed: 31451496
DOI: 10.1128/AAC.02690-18 -
Journal of Investigative Medicine High... 2022Recurrent vulvovaginal candidiasis is a common disorder which causes significant morbidity among women worldwide, and treatment options are limited. Ibrexafungerp is a...
Recurrent vulvovaginal candidiasis is a common disorder which causes significant morbidity among women worldwide, and treatment options are limited. Ibrexafungerp is a novel antifungal agent which was approved in 2021 for treatment of vulvovaginal candidiasis. We present a case of recurrent vulvovaginal candidiasis successfully treated with ibrexafungerp.
Topics: Antifungal Agents; Candidiasis, Vulvovaginal; Drug Resistance, Fungal; Female; Fluconazole; Glycosides; Humans; Triterpenes
PubMed: 36059275
DOI: 10.1177/23247096221123144 -
Antimicrobial Agents and Chemotherapy Jan 2024Vulvovaginal candidiasis (VVC) is a common condition among women. Fluconazole remains the dominant treatment option for VVC. Oteseconazole is a highly selective... (Randomized Controlled Trial)
Randomized Controlled Trial
Vulvovaginal candidiasis (VVC) is a common condition among women. Fluconazole remains the dominant treatment option for VVC. Oteseconazole is a highly selective inhibitor of fungal CYP51. This randomized, double-blinded, phase 3 trial was conducted to evaluate the efficacy and safety of oteseconazole compared with fluconazole in treating severe VVC. Female subjects presenting with vulvovaginal signs and symptoms score of ≥7 and positive infection determined by potassium hydroxide test or Gram staining were randomly assigned to receive oteseconazole (600 mg on D1 and 450 mg on D2) or fluconazole (150 mg on D1 and D4) in a 1:1 ratio. The primary endpoint was the proportion of subjects achieving therapeutic cure [defined as achieving both clinical cure (absence of signs and symptoms of VVC) and mycological cure (negative culture of species)] at D28. A total of 322 subjects were randomized and 321 subjects were treated. At D28, a statistically significantly higher proportion of subjects achieved therapeutic cure in the oteseconazole group than in the fluconazole group (66.88% vs 45.91%; = 0.0002). Oteseconazole treatment resulted in an increased proportion of subjects achieving mycological cure (82.50% vs 59.12%; < 0.0001) and clinical cure (71.25% vs 55.97%; = 0.0046) compared with fluconazole. The incidence of treatment-emergent adverse events was similar between the two groups. No subjects discontinued study treatment or withdrew study due to adverse events. Oteseconazole showed statistically significant and clinically meaningful superiority over fluconazole for the treatment of severe VVC and was generally tolerated.
Topics: Female; Humans; Fluconazole; Candidiasis, Vulvovaginal; Antifungal Agents; Candida; Administration, Oral; Candida albicans
PubMed: 38095426
DOI: 10.1128/aac.00778-23 -
BMC Infectious Diseases Apr 2020Accurate identification Candida is important for successful therapy and epidemiology study. The aim of research is to study API 20C yeast identification system...
BACKGROUND
Accurate identification Candida is important for successful therapy and epidemiology study. The aim of research is to study API 20C yeast identification system identification rate by using molecular identification as gold standard and tested the antifungal susceptibility of Candida from patients with vulvovaginal candidiasis (VVC).
METHODS
In total, 3574 yeast isolates were obtained from patients with VVC. API 20C yeast identification, molecular identification and in vitro antifungal susceptibility were performed.
RESULTS
C. albicans was the predominant Candida species [2748 isolates, 76.9%] in VVC. The isolates from vaginal samples represented 22 species based on molecular identification. The API 20C system identifies only 11 of the species encountered during the study period. Based on the API 20C system, 3273 (91.78%) isolates were correctly identified to the species level. The correct identification rate of the API 20C system for rare yeast was 15.29% (26/170 isolates). Antifungal susceptibility was tested in a total of 1844 isolates of Candida from patients with VVC. C. albicans was susceptible to most of the tested antifungals. The MICs of azoles for C. glabrata were higher than those for C. albicans. The MICs of echinocandins for C. parapsilosis were higher than those for C. albicans.
CONCLUSIONS
The API 20C yeast identification system can be used to reliably identify the most common Candida species while molecular methods are necessary for the identification of closely related, emerging, and rare yeast species. The results from this study suggest that much of the previous studies on the epidemiology of VVC should be re-thought. C. albicans was susceptible to most of the tested antifungals.
Topics: Adult; Antifungal Agents; Candida; Candidiasis, Vulvovaginal; China; Drug Resistance, Multiple, Fungal; Female; Humans; Microbial Sensitivity Tests; Polymerase Chain Reaction; Prevalence; Prospective Studies; Young Adult
PubMed: 32393342
DOI: 10.1186/s12879-020-04985-w