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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 -
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 -
Infection and Immunity Mar 2024Vulvovaginal candidiasis (VVC), caused by is characterized by aberrant inflammation by polymorphonuclear neutrophils (PMNs) in the vaginal lumen. Data from the...
Vulvovaginal candidiasis (VVC), caused by is characterized by aberrant inflammation by polymorphonuclear neutrophils (PMNs) in the vaginal lumen. Data from the established murine model shows that despite potent antifungal properties, PMNs fail to clear due to local heparan sulfate that inhibits the interaction between PMNs and , resulting in chronic vaginal immunopathology. To understand the role of neutrophil extracellular traps (NETs) in defense against at the vaginal mucosa, we investigated the NET-forming capacity of PMNs in chronic VVC-susceptible (CVVC-S/C3H) and -resistant (CVVC-R/CD-1) mouse strains. Immunofluorescence revealed the formation of NETs (release of DNA with PMN-derived antimicrobial proteins) in PMN cocultures using vaginal conditioned medium (VCM) generated from CVVC-R/CD-1 mice, similar to NET-inducing positive controls. Under these NETotic conditions, PMNs released high levels of double-stranded DNA bound with NET-associated proteins, concomitant with substantial killing activity. In contrast, PMN cocultures in VCM from CVVC-S/C3H mice lacked NET formation together with reduced antifungal activity. Similar results were observed : active NET interaction followed by fungal clearance in inoculated CVVC-R/CD-1 mice, and sustained high vaginal fungal burden and no evidence of NETs in inoculated CVVC-S/C3H mice. Furthermore, the level of Ki67 expression, a putative NETotic PMN marker, was significantly reduced in vaginal lavage fluid from CVVC-S/C3H mice compared to CVVC-R/CD-1 mice. Finally, scanning electron microscopy revealed that PMNs in CVVC-R, but not CVVC-S, conditions exhibited NETs in direct contact with hyphae and . These results suggest that VVC-associated immunopathology includes impaired NET-mediated antifungal activity.
Topics: Female; Humans; Animals; Mice; Candidiasis, Vulvovaginal; Extracellular Traps; Antifungal Agents; Disease Models, Animal; Mice, Inbred C3H; Candida albicans
PubMed: 38289125
DOI: 10.1128/iai.00350-23 -
Journal of Natural Products Feb 2024The rise of multidrug resistant fungal infections highlights the need to identify and develop novel antifungal agents. Occidiofungin is a nonribosomally synthesized...
The rise of multidrug resistant fungal infections highlights the need to identify and develop novel antifungal agents. Occidiofungin is a nonribosomally synthesized glycolipopeptide that has a unique mechanism of action, disrupting actin-mediated functions and inducing cellular apoptosis. Antifungal activity has been observed in vitro against various fungal species, including multidrug resistant , and in vivo efficacy has been demonstrated in a murine vulvovaginal candidiasis model. Occidiofungin, a cyclic glycolipopeptide, is composed of eight amino acids and in previous studies, an asparagine residue was assigned at position 7 (ASN7). In this study, new structural variants of occidiofungin have been characterized which have aspartic acid (ASP7), glutamine (GLN7), or glutamic acid (GLU7) at position 7. The side chain of the ASP7 variant contains the only terminal carboxylic acid in the peptide and provides a useful site for selective chemical modifications. Analogues were synthesized at the ASP7 position and tested for antifungal activity. These analogues were shown to be more active as compared to the ASP7 variant against a panel of species. The naturally occurring variants of occidiofungin with a side chain containing a carboxylic acid at the seventh amino acid position can be used to develop semisynthetic analogues with enhanced therapeutic properties.
Topics: Mice; Animals; Antifungal Agents; Burkholderia; Carboxylic Acids; Microbial Sensitivity Tests; Glycopeptides; Peptides, Cyclic
PubMed: 38277493
DOI: 10.1021/acs.jnatprod.3c00777 -
Microorganisms Jan 2024Among the infectious causes of vulvovaginal symptoms, bacterial vaginosis (BV) and vulvovaginal candidiasis (VVC) dominate. Apart from infrequent mixed infections, both... (Review)
Review
Among the infectious causes of vulvovaginal symptoms, bacterial vaginosis (BV) and vulvovaginal candidiasis (VVC) dominate. Apart from infrequent mixed infections, both are considered independent and caused by unrelated pathogenic mechanisms. Clinical experience, however, is strongly suggestive that in some populations these infections are linked with recurrent BV (RBV) serving as the dominant etiopathogenic trigger for development of recurrent VVC (RVVC) with profound clinical and therapeutic consequences. The biologic basis for this critical interrelationship is discussed and suggests that as a consequence of BV dysbiosis, and not necessarily because of antibiotics prescribed, immune defenses are compromised, neutralizing vaginal yeast tolerance. The consequent BV-induced vaginal proinflammatory environment predisposes to mixed infection or consecutive episodes of post-treatment VVC. Recurrent BV and repeated antimicrobial drug exposure also predispose to acquired fluconazole resistance in isolates, contributing to refractory vulvovaginal candidiasis.
PubMed: 38257934
DOI: 10.3390/microorganisms12010108 -
Microbiological Research Apr 2024Vaginal infectious diseases caused by viruses and bacteria have been linked to the occurrence of dysbiosis, that is, a reduction in the abundance of the normally... (Review)
Review
A molecular view on the interference established between vaginal Lactobacilli and pathogenic Candida species: Challenges and opportunities for the development of new therapies.
Vaginal infectious diseases caused by viruses and bacteria have been linked to the occurrence of dysbiosis, that is, a reduction in the abundance of the normally dominating vaginal Lactobacillus species. Mucosal infections in the vagina and/or vulva caused by Candida species, usually known as vulvovaginal candidiasis (or VVC), are among the leading causes of diseases in the vaginal tract. The existence of a clear link between the occurrence of dysbiosis and the development of VVC is still unclear, although multiple observations point in that direction. Based on the idea that vaginal health is linked to a microbiota dominated by lactobacilli, several probiotics have been used in management of VVC, either alone or in combination with antifungals, having obtained different degrees of success. In most cases, the undertaken trials resorted to lactobacilli species other than those indigenous to the vaginal tract, although in vitro these vaginal species were shown to reduce growth, viability and virulence of Candida. In this paper we overview the role of lactobacilli and Candida in the vaginal micro- and myco-biomes, while discussing the results obtained in what concerns the establishment of interference mechanisms in vivo and the environmental factors that could determine that. We also overview the molecular mechanisms by which lactobacilli species have been shown to inhibit pathophysiology of Candida, including the description of the genes and pathways determining their ability to thrive in the presence of each other. In a time where concerns are increasing with the emergence of antifungal resistance and the slow pace of discovery of new antifungals, a thorough understanding of the molecular mechanisms underneath the anti-Candida effect prompted by vaginal lactobacilli is of utmost importance to assure a knowledge-based design of what can be a new generation of pharmaceuticals, eventually focusing therapeutic targets other than the usual ones.
Topics: Female; Humans; Candida; Lactobacillus; Antifungal Agents; Dysbiosis; Vagina; Candidiasis, Vulvovaginal; Candida albicans
PubMed: 38246122
DOI: 10.1016/j.micres.2024.127628 -
European Review For Medical and... Jan 2024To investigate the non-inferiority of efficacy and tolerability of Lactobacillus plantarum P 17630 soft vaginal capsules compared to the antifungal therapy with... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
To investigate the non-inferiority of efficacy and tolerability of Lactobacillus plantarum P 17630 soft vaginal capsules compared to the antifungal therapy with miconazole nitrate 400 mg soft vaginal capsules in patients with symptomatic vulvovaginal infection due to Candida.
PATIENTS AND METHODS
Adult women with vulvovaginal candidiasis were randomized to either L. plantarum P17630 100,000,000 CFU soft vaginal capsules by vaginal route each day for 3 or 6 consecutive days or miconazole nitrate 400 mg soft vaginal capsule. Visual Analog Scale (VAS) scores for vaginitis symptoms were used, and vaginal fluid interleukin 6 (IL6) was dosed. The study was registered in EudraCT database (code LPP17630-C-018; number: 2018-003095-12).
RESULTS
200 patients were included in the study. The mean VAS scores for vaginitis symptoms were progressively reduced in both treatment groups at each visit, without significant difference between groups (p>0.05 for each symptom, at each time point). The efficacy of L. plantarum and the reference medicinal product was maintained at follow-up (day 21). The mean concentration of IL-6 decreased from visit 1 to visit 3 in both groups without a significant difference (p>0.05). No adverse events were reported.
CONCLUSIONS
L. plantarum P17630 100,000,000 CFU soft vaginal capsules are effective and safe for treating vaginal candidiasis without the concomitant use of an antifungal product, which rules out the risk of antimicrobic resistance. The long-term effect on vaginal microflora may add the possibility of reducing the risk of recurrences.
Topics: Adult; Female; Humans; Antifungal Agents; Candidiasis, Vulvovaginal; Lactobacillus plantarum; Miconazole; Vagina; Vulvovaginitis
PubMed: 38235890
DOI: 10.26355/eurrev_202401_34927 -
Indian Journal of Sexually Transmitted... 2023Sexually transmitted diseases (STDs) continue to be a major public health problem with significant burden on the society. Some of this can be attributed to our lack of...
INTRODUCTION
Sexually transmitted diseases (STDs) continue to be a major public health problem with significant burden on the society. Some of this can be attributed to our lack of knowledge about the change of disease spectrum from time to time.
AIMS
The aim of the study was to understand the changing pattern of STDs over the past 17 years (2003-2019).
MATERIALS AND METHODS
It was a retrospective study where data of patients who attended our Suraksha Clinic from 2003 to 2019 were collected. All the cases were subjected to detailed history, examination, and investigations done to rule out STDs.
RESULTS
A total of 2436 patients were included in the study. The majority of the patients were in the age group of 18-30 years. The most frequent diagnosis was vulvovaginal candidiasis, followed by herpes genitalis. 3.3% of patients had human immunodeficiency virus. 4.8% of patients were men sex men (MSM). Overall, viral STDs were most common, followed by fungal and bacterial. To understand the changing trends, data were divided into different phases according to the time period. During Phase 1 (2003-2007), viral STDs were most common, followed by bacterial and fungal. However, this trend changed in Phase 4 (2016-2019) and fungal STDs became most common.
CONCLUSIONS
Despite numerous health initiatives, the number of STD cases is rising day by day. The increasing number of MSM over the study period necessitates dedicated efforts to address the health needs of this population. The National AIDS Control Organization should take necessary measures and steps to address the overall increase in STDs considering recent trends showing a drop in bacterial STDs and an increase in fungal and viral STDs.
PubMed: 38223154
DOI: 10.4103/ijstd.ijstd_100_22 -
Taiwanese Journal of Obstetrics &... Jan 2024Probiotics, live microorganisms that confer health benefits to the host when administered in adequate amounts, have gained considerable attention for their potential... (Review)
Review
Probiotics, live microorganisms that confer health benefits to the host when administered in adequate amounts, have gained considerable attention for their potential role in maintaining women's health. This overview summarizes key clinical findings on the beneficial effects of probiotics in various aspects of women's health. Probiotics, particularly Lactobacillus species, contribute to vaginal health by promoting a balanced vaginal microbiome to prevent infections and maintain an acidic environment. In gynecologic conditions, probiotics show potential in preventing and managing bacterial vaginosis, vulvovaginal candidiasis, and sexually transmitted infections. Probiotic supplementation has also been associated with improvements in metabolic parameters and menstrual irregularities in polycystic ovary syndrome patients. During pregnancy, probiotics may be helpful in reducing the risk of gestational diabetes, maternal group B streptococcal colonization, obstetric anemia, and postpartum mastitis. In recent years, the potential role of probiotics in the prevention and management of gynecologic cancer has gained attention. Further research is needed to better understand the specific mechanisms and determine the optimal Lactobacillus strains and dosages regimens for gynecologic cancer prevention and therapy. In conclusion, probiotics offer a non-invasive and cost-effective approach to support women's health and prevent obstetric and gynecologic complications.
Topics: Pregnancy; Female; Humans; Women's Health; Vagina; Vaginosis, Bacterial; Probiotics; Lactobacillus; Polycystic Ovary Syndrome
PubMed: 38216265
DOI: 10.1016/j.tjog.2023.09.018 -
Applied Microbiology and Biotechnology Dec 2024Vulvovaginal candidiasis (VVC) affects approximately 30-50% of women at least once during their lifetime, causing uncomfortable symptoms and limitations in their daily...
Vulvovaginal candidiasis (VVC) affects approximately 30-50% of women at least once during their lifetime, causing uncomfortable symptoms and limitations in their daily quality of life. Antifungal therapy is not very effective, does not prevent recurrencies and usually causes side effects. Therefore, alternative therapies are urgently needed. The goal of this work was to investigate the potential benefits of using mannan oligosaccharides (MOS) extracts together with a Lactobacillus sp. pool, composed by the most significant species present in the vaginal environment, to prevent infections by Candida albicans. Microbial growth of isolated strains of the main vaginal lactobacilli and Candida strains was assessed in the presence of MOS, to screen their impact upon growth. A pool of the lactobacilli was then tested against C. albicans in competition and prophylaxis studies; bacterial and yeast cell numbers were quantified in specific time points, and the above-mentioned studies were assessed in simulated vaginal fluid (SVF). Finally, adhesion to vaginal epithelial cells (HeLa) was also evaluated, once again resorting to simultaneous exposure (competition) or prophylaxis assays, aiming to measure the effect of MOS presence in pathogen adherence. Results demonstrated that MOS extracts have potential to prevent vaginal candidiasis in synergy with vaginal lactobacilli, with improved results than those obtained when using lactobacilli alone. KEY POINTS: Potential benefits of MOS extracts with vaginal lactobacilli to prevent C. albicans infections. MOS impacts on growth of vaginal lactobacilli pool and C. albicans in SVF. MOS extracts in synergy with L. crispatus inhibit C. albicans adhesion in HeLa cells.
Topics: Female; Humans; Candida albicans; Mannans; HeLa Cells; Quality of Life; Candidiasis, Vulvovaginal; Lactobacillus
PubMed: 38194142
DOI: 10.1007/s00253-023-12909-2