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Antonie Van Leeuwenhoek Feb 2024Vulvovaginal candidiasis is the second most common vaginal infection caused by drug-resistant Candida species that affects about 70-75% of reproductive age group women...
Vulvovaginal candidiasis is the second most common vaginal infection caused by drug-resistant Candida species that affects about 70-75% of reproductive age group women across the globe. As current-day antifungal drugs are ineffective against the biofilms formed by the drug-resistant Candida strains, several natural compounds and antagonistic microbes are being explored as alternative antifungal agents. In the present study, we investigated the anti-biofilm activity of Cell-Free Supernatant (CFS) extracted from the commercially available probiotics VSL-3 against the biofilms of Candida species and also evaluated their efficacy in curbing the yeast-to-hyphal transition. Various methodologies like crystal violet staining and scanning electron microscopy were used to study the effect of CFS against the biofilms formed by the species. The ability of CFS to interfere with yeast to hyphal transition in Candida was studied by colony morphology assay and visually confirmed with phase contrast microscopy. The potential of the CFS of the probiotics was also evaluated using goat buccal tissue, a novel ex-vivo model that mimics the vaginal environment. Moreover, the supernatant extracted from VSL-3 had the ability to down-regulate the expression of virulence genes of Candida from the biofilm formed over the ex-vivo model. These results emphasize the anti-fungal and anti-infective properties of the CFS of VSL-3 against drug-resistant Candida strains causing vulvovaginal candidiasis.
Topics: Female; Humans; Candidiasis, Vulvovaginal; Candida; Saccharomyces cerevisiae; Antifungal Agents; Biofilms; Probiotics; Candida albicans
PubMed: 38367023
DOI: 10.1007/s10482-024-01929-1 -
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 -
Journal of Family Medicine and Primary... Dec 2023Vulvovaginal candidiasis (VVC) is considered a common gynecological problem among females of reproductive age group. 70-75% of women report having had candidal...
Phenotypic characterization and antifungal susceptibility profile of Candida isolates from women with vulvovaginal candidiasis at a community health center linked to a teaching institution in the Sub-Himalayan region of North India.
INTRODUCTION
Vulvovaginal candidiasis (VVC) is considered a common gynecological problem among females of reproductive age group. 70-75% of women report having had candidal vulvovaginitis at some point in their lifetimes and 40-50% suffer recurrent candidal vulvovaginitis.
OBJECTIVES
This study aims to identify the Candida species involved in VVC and to determine their antifungal susceptibility pattern.
MATERIALS AND METHODS
The present study was a cross-sectional study conducted on 257 females (18-55 yr) with complaints of abnormal vaginal discharge. For detection of Candida, the swab samples were subjected to Gram stain, 10% KOH mount, and culture on Sabouraud dextrose agar (SDA). species identification was done by subculturing isolates onto CHROMagar, corn meal agar (Himedia), and further confirmation was done by MALDI-TOF MS. Antifungal testing was done using the disk diffusion method.
RESULTS
A total of 257 females with complaints of abnormal discharge were enrolled in this study. Out of 257, 37 (58.7%) and 26 (41.3%) isolates were identified as non-albicans . Out of 63 positive cases, a maximum number of study subject belongs to the age group 26-35 years (50.8%). Along with vaginal discharge, itching (65.37%) is the most common complaint. VVC was found to be most predominant in patients with prolonged antibiotic therapy (38.1%), and in pregnant females (15.9%).
CONCLUSION
Understanding the emerging fungal pathogens and their drug susceptibility patterns is essential for the effective management of infections. Drug resistance can lead to treatment failure and highlights the need for alternative treatment options or strategies.
PubMed: 38361850
DOI: 10.4103/jfmpc.jfmpc_1082_23 -
Beneficial Microbes Nov 2023The development of probiotics has now included the areas along the gut-vaginal axis. We thus aimed to investigate the effects of lactobacilli probiotic to modulate and... (Randomized Controlled Trial)
Randomized Controlled Trial
The development of probiotics has now included the areas along the gut-vaginal axis. We thus aimed to investigate the effects of lactobacilli probiotic to modulate and restore vaginal and gut microbiota of pregnant women with vaginal candidiasis (VC). A randomised, double-blind and placebo-controlled study was performed in 78 pregnant women with VC. Patients were randomised to either the probiotic (SynForU-HerCare) or placebo which were administered at baseline and continued for 8-weeks (two capsules/day of 9.5 log cfu/capsule). Microbiota profiles were assessed at time points of weeks-0, 4 and 8 for high vaginal swab and faecal samples. Shannon diversity index showed that after 8-weeks amid VC, a shift in microbial community compositional changes occurred in the high vaginal region at both genus (P=0.025) and species (P=0.044) levels, where the administration of probiotic prevented such a shift. These changes were mainly attributed to a decreased in abundance of Lactobacillus (P=0.042) accompanied by increased abundance of Prevotella (P=0.002) and Atopobium (P=0.002) in the placebo group while the probiotic group remained unchanged over time. The administration of probiotics also prevented a reduced abundance of faecal phylum Firmicutes after 8-weeks as seen in the placebo group (P<0.0001), which also showed reduction at subsequent taxonomic levels of class, family, genera and species. VC has not only altered the microbiota of vagina regions but also gut microbiota profiles, causing lessening of gut microbiota that are crucial for gut nutrient availability, protection and immunity. The administration of lactobacilli probiotics has prevented such a shift, leading to better modulated gut and vaginal microenvironment amid VC. The study was registered at ClinicalTrials.gov: identifier number NCT03940612.
Topics: Female; Humans; Pregnancy; Candidiasis, Vulvovaginal; Gastrointestinal Microbiome; Lactobacillus; Pregnant Women; Probiotics; Vagina; Vaginosis, Bacterial; Double-Blind Method
PubMed: 38350486
DOI: 10.1163/18762891-20220103 -
Archives of Microbiology Feb 2024Candida albicans is a commensal fungus that infects the humans and becomes an opportunistic pathogen particularly in immuno-compromised patients. Among the Candida... (Review)
Review
Candida albicans is a commensal fungus that infects the humans and becomes an opportunistic pathogen particularly in immuno-compromised patients. Among the Candida genus, yeast C. albicans is the most frequently incriminated species and is responsible for nearly 50-90% of human candidiasis, with vulvovaginal candidiasis alone, affecting about 75% of the women worldwide. One of the significant virulence traits in C. albicans is its tendency to alternate between the yeast and hyphae morphotypes, accounting for the development of multi-drug resistance in them. Thus, a thorough comprehension of the decision points and genes controlling this transition is necessary, to understand the pathogenicity of this, naturally occurring, pernicious fungus. Additionally, the formation of C. albicans biofilm is yet another pathogenesis trait and a paramount cause of invasive candidiasis. Since 1980 and in 90 s, wide spread use of immune-suppressing therapies and over prescription of fluconazole, a drug used to treat chronic fungal infections, triggered the emergence of novel anti-fungal drug development. Thus, this review thoroughly elucidates the diseases associated with C. albicans infection as well as the anti-fungal resistance mechanism associated with them and identifies the emerging therapeutic agents, along with a rigorous discussion regarding the future strategies that can possibly be adopted for the cure of this deleterious pathogen.
Topics: Humans; Female; Candida albicans; Antifungal Agents; Candidiasis; Candida; Drug Resistance, Fungal; Persistent Infection
PubMed: 38349529
DOI: 10.1007/s00203-023-03824-1 -
MBio Mar 2024can cause mucosal infections in humans. This includes oropharyngeal candidiasis, which is commonly observed in human immunodeficiency virus infected patients, and...
can cause mucosal infections in humans. This includes oropharyngeal candidiasis, which is commonly observed in human immunodeficiency virus infected patients, and vulvovaginal candidiasis (VVC), which is the most frequent manifestation of candidiasis. Epithelial cell invasion by hyphae is accompanied by the secretion of candidalysin, a peptide toxin that causes epithelial cell cytotoxicity. During vaginal infections, candidalysin-driven tissue damage triggers epithelial signaling pathways, leading to hyperinflammatory responses and immunopathology, a hallmark of VVC. Therefore, we proposed blocking candidalysin activity using nanobodies to reduce epithelial damage and inflammation as a therapeutic strategy for VVC. Anti-candidalysin nanobodies were confirmed to localize around epithelial-invading hyphae, even within the invasion pocket where candidalysin is secreted. The nanobodies reduced candidalysin-induced damage to epithelial cells and downstream proinflammatory responses. Accordingly, the nanobodies also decreased neutrophil activation and recruitment. mathematical modeling enabled the quantification of epithelial damage caused by candidalysin under various nanobody dosing strategies. Thus, nanobody-mediated neutralization of candidalysin offers a novel therapeutic approach to block immunopathogenic events during VVC and alleviate symptoms.IMPORTANCEWorldwide, vaginal infections caused by (VVC) annually affect millions of women, with symptoms significantly impacting quality of life. Current treatments are based on anti-fungals and probiotics that target the fungus. However, in some cases, infections are recurrent, called recurrent VVC, which often fails to respond to treatment. Vaginal mucosal tissue damage caused by the peptide toxin candidalysin is a key driver in the induction of hyperinflammatory responses that fail to clear the infection and contribute to immunopathology and disease severity. In this pre-clinical evaluation, we show that nanobody-mediated candidalysin neutralization reduces tissue damage and thereby limits inflammation. Implementation of candidalysin-neutralizing nanobodies may prove an attractive strategy to alleviate symptoms in complicated VVC cases.
Topics: Humans; Female; Candidiasis, Vulvovaginal; Quality of Life; Single-Domain Antibodies; Candida albicans; Candidiasis; Inflammation; Fungal Proteins
PubMed: 38349176
DOI: 10.1128/mbio.03409-23 -
BMC Microbiology Feb 2024Candida albicans is the most common fungus that causes vaginal candidiasis in immunocompetent women and catastrophic infections in immunocompromised patients. The...
BACKGROUND
Candida albicans is the most common fungus that causes vaginal candidiasis in immunocompetent women and catastrophic infections in immunocompromised patients. The treatment of such infections is hindered due to the increasing emergence of resistance to azoles in C. albicans. New treatment approaches are needed to combat candidiasis especially in the dwindled supply of new effective and safe antifungals. The resistance to azoles is mainly attributed to export of azoles outside the cells by means of the efflux pump that confers cross resistance to all azoles including fluconazole (FLC).
OBJECTIVES
This study aimed to investigate the possible efflux pump inhibiting activity of fusidic acid (FA) in C. albicans resistant isolates and the potential use of Fusidic acid in combination with fluconazole to potentiate the antifungal activity of fluconazole to restore its activity in the resistant C. albicans isolates.
METHODS
The resistance of C. albicans isolates was assessed by determination of minimum inhibitory concentration. The effect of Fusidic acid at sub-inhibitory concentration on efflux activity was assayed by rhodamine 6G efflux assay and intracellular accumulation. Mice model studies were conducted to evaluate the anti-efflux activity of Fusidic acid and its synergistic effects in combination with fluconazole. Impact of Fusidic acid on ergosterol biosynthesis was quantified. The synergy of fluconazole when combined with Fusidic acid was investigated by determination of minimum inhibitory concentration. The cytotoxicity of Fusidic acid was tested against erythrocytes. The effect of Fusidic acid on efflux pumps was tested at the molecular level by real-time PCR and in silico study. In vivo vulvovaginitis mice model was used to confirm the activity of the combination in treating vulvovaginal candidiasis.
RESULTS
Fusidic acid showed efflux inhibiting activity as it increased the accumulation of rhodamine 6G, a substrate for ABC-efflux transporter, and decreased its efflux in C. albicans cells. The antifungal activity of fluconazole was synergized when combined with Fusidic acid. Fusidic acid exerted only minimal cytotoxicity on human erythrocytes indicating its safety. The FA efflux inhibitory activity could be owed to its ability to interfere with efflux protein transporters as revealed by docking studies and downregulation of the efflux-encoding genes of both ABC transporters and MFS superfamily. Moreover, in vivo mice model showed that using fluconazole-fusidic acid combination by vaginal route enhanced fluconazole antifungal activity as shown by lowered fungal burden and a negligible histopathological change in vaginal tissue.
CONCLUSION
The current findings highlight FA's potential as a potential adjuvant to FLC in the treatment of vulvovaginal candidiasis.
Topics: Humans; Female; Animals; Mice; Fluconazole; Antifungal Agents; Candidiasis, Vulvovaginal; Fusidic Acid; Fungal Proteins; Drug Resistance, Fungal; Candida albicans; Candidiasis; ATP-Binding Cassette Transporters; Azoles; Microbial Sensitivity Tests
PubMed: 38341568
DOI: 10.1186/s12866-024-03181-z -
Medicine Feb 2024This study aims to investigate the relationship between the human papillomavirus (HPV) infection and the altered vaginal microecological environment of patients....
This study aims to investigate the relationship between the human papillomavirus (HPV) infection and the altered vaginal microecological environment of patients. Initially, HPV genotyping and microecological detection were performed in 1281 subjects in the Department of Obstetrics and Gynecology of The First Hospital of Qinhuangdao (Qinhuangdao, China). The relationship between the enzymes of vaginal microecology, that is, proline aminopeptidase and acetylglucosaminidase, and vaginal inflammatory diseases, as well as the prognosis of HPV infection, was analyzed. The experimental findings indicated a close relationship between the expression of positive prolyl aminopeptidase and trichomonas vaginitis, as well as bacterial vaginitis. In addition, the expression of acetylglucosaminidase is closely associated with trichomonas vaginitis and vulvovaginal candidiasis. Furthermore, the observations indicated that positive prolyl aminopeptidase and acetylglucosaminidase could increase the risk of various subtypes of HPV infection in patients. The receiver operating characteristic curve analysis presented that the expression of prolyl aminopeptidase and acetylglucosaminidase could offer exceptional diagnostic efficacy, indicating their association with persistent HPV infection. In summary, our results highlighted that the expression of positive prolyl aminopeptidase and acetylglucosaminidase in the vaginal microecology could be substantially correlated to the occurrence and the development of vaginal inflammatory diseases, as well as the outcome and the risk of persistent HPV infection.
Topics: Female; Pregnancy; Humans; Trichomonas Vaginitis; Papillomavirus Infections; Acetylglucosaminidase; Vagina; Human Papillomavirus Viruses
PubMed: 38335425
DOI: 10.1097/MD.0000000000037068 -
The Medical Clinics of North America Mar 2024Recurrent infectious vaginitis can lead to significant morbidity, patient frustration, and health care costs. The most common causes are bacterial vaginosis (BV) and... (Review)
Review
Recurrent infectious vaginitis can lead to significant morbidity, patient frustration, and health care costs. The most common causes are bacterial vaginosis (BV) and vulvovaginal candidiasis (VVC); however, other infectious and noninfectious etiologies should be considered in patients with recurrent symptoms. A detailed history and physical examination with appropriate testing at the time of symptoms is critical to establishing a correct diagnosis. Management options for recurrent BV and VVC are limited. Complex cases including those with atypical symptoms, negative testing for common causes, refractory symptoms despite appropriate therapy or recurrences during suppressive therapy will require referral to specialist care.
Topics: Female; Humans; Vaginosis, Bacterial; Candidiasis, Vulvovaginal; Primary Health Care
PubMed: 38331486
DOI: 10.1016/j.mcna.2023.08.017 -
PloS One 2024Helicobacter pylori infections are generally acquired during childhood and affect half of the global population, but its transmission route remains unclear. It is...
BACKGROUND
Helicobacter pylori infections are generally acquired during childhood and affect half of the global population, but its transmission route remains unclear. It is reported that H. pylori can be internalized into Candida, but more evidence is needed for the internalization of H. pylori in human gastrointestinal Candida and vaginal Candida.
METHODS
Candida was isolated from vaginal discharge and gastric mucosa biopsies. We PCR-amplified and sequenced H. pylori-specific genes from Candida genomic DNA. Using optical and immunofluorescence microscopy, we identified and observed bacteria-like bodies (BLBs) in Candida isolates and subcultures. Intracellular H. pylori antigen were detected by immunofluorescence using Fluorescein isothiocyanate (FITC)-labeled anti-H. pylori IgG antibodies. Urease activity in H. pylori internalized by Candida was detected by inoculating with urea-based Sabouraud dextrose agar, which changed the agar color from yellow to pink, indicating urease activity.
RESULTS
A total of 59 vaginal Candida and two gastric Candida strains were isolated from vaginal discharge and gastric mucosa. Twenty-three isolates were positive for H. pylori 16S rDNA, 12 were positive for cagA and 21 were positive for ureA. The BLBs could be observed in Candida cells, which were positive for H. pylori 16S rDNA, and were viable determined by the LIVE/DEAD BacLight Bacterial Viability kit. Fluorescein isothiocyanate (FITC)-conjugated antibodies could be reacted specifically with H. pylori antigen inside Candida cells by immunofluorescence. Finally, H. pylori-positive Candida remained positive for H. pylori 16S rDNA even after ten subcultures. Urease activity of H. pylori internalized by Candida was positive.
CONCLUSION
In the form of BLBs, H. pylori can internalize into gastric Candida and even vaginal Candida, which might have great significance in its transmission and pathogenicity.
Topics: Female; Humans; Helicobacter pylori; Urease; Helicobacter Infections; Fluorescein-5-isothiocyanate; Agar; Antigens, Bacterial; Gastric Mucosa; Candida; Biopsy; Candidiasis, Vulvovaginal; DNA, Ribosomal; Vaginal Discharge; Urea; Bacterial Proteins
PubMed: 38329956
DOI: 10.1371/journal.pone.0298442