Vulvovaginitis Caused by Candida Species Following Antibiotic Exposure

Shukla, Asmita; Sobel, Jack D.

doi:10.1007/s11908-019-0700-y

Cited by 35 publications

(32 citation statements)

References 28 publications

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“…Clinical studies have demonstrated that MV140 significantly prevents RUTIs in 80% to 90% of individuals during the year following vaccination (39)(40)(41)(42)(43). The reported clinical benefits indicate that sublingual administration of MV140 also reduces the overuse of antibiotics, which not only might reduce the increase in antibiotic-resistances (40), but also avoid microbiota disruption (1,7,(9)(10)(11)(12). Due to the high incidence of RVVCs and the difficulties for their treatment, mainly based on antifungals, new approaches to combat these infections are also fully demanded.…”

Section: Discussionmentioning

confidence: 99%

“…The overuse of antibiotics is also associated with dysregulation of normal vagina and gastrointestinal microbiota, which favor pathogen invasion and subsequent bacterial and fungal infection (1,3,7). Due to microbiota alterations, opportunistic pathogens such as Candida albicans colonize the vaginal tract generating vulvovaginal candidiasis (VVCs) (8)(9)(10)(11)(12). More than 70% of women worldwide suffer from VVCs (with maximum incidence between 20 and 40 years old) and around 5% experience recurrent infections (RVVCs), defined as four or more episodes per year (13)(14)(15)(16).…”

Section: Introductionmentioning

confidence: 99%

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A Combination of Polybacterial MV140 and Candida albicans V132 as a Potential Novel Trained Immunity-Based Vaccine for Genitourinary Tract Infections

et al. 2021

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Recurrent urinary tract infections (RUTIs) and recurrent vulvovaginal candidiasis (RVVCs) represent major healthcare problems with high socio-economic impact worldwide. Antibiotic and antifungal prophylaxis remain the gold standard treatments for RUTIs and RVVCs, contributing to the massive rise of antimicrobial resistance, microbiota alterations and co-infections. Therefore, the development of novel vaccine strategies for these infections are sorely needed. The sublingual heat-inactivated polyvalent bacterial vaccine MV140 shows clinical efficacy for the prevention of RUTIs and promotes Th1/Th17 and IL-10 immune responses. V132 is a sublingual preparation of heat-inactivated Candida albicans developed against RVVCs. A vaccine formulation combining both MV140 and V132 might well represent a suitable approach for concomitant genitourinary tract infections (GUTIs), but detailed mechanistic preclinical studies are still needed. Herein, we showed that the combination of MV140 and V132 imprints human dendritic cells (DCs) with the capacity to polarize potent IFN-γ– and IL-17A–producing T cells and FOXP3+ regulatory T (Treg) cells. MV140/V132 activates mitogen-activated protein kinases (MAPK)-, nuclear factor-κB (NF-κB)- and mammalian target of rapamycin (mTOR)-mediated signaling pathways in human DCs. MV140/V132 also promotes metabolic and epigenetic reprogramming in human DCs, which are key molecular mechanisms involved in the induction of innate trained immunity. Splenocytes from mice sublingually immunized with MV140/V132 display enhanced proliferative responses of CD4+ T cells not only upon in vitro stimulation with the related antigens contained in the vaccine formulation but also upon stimulation with phytohaemagglutinin. Additionally, in vivo sublingual immunization with MV140/V132 induces the generation of IgG and IgA antibodies against all the components contained in the vaccine formulation. We uncover immunological mechanisms underlying the potential mode of action of a combination of MV140 and V132 as a novel promising trained immunity-based vaccine (TIbV) for GUTIs.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A Combination of Polybacterial MV140 and Candida albicans V132 as a Potential Novel Trained Immunity-Based Vaccine for Genitourinary Tract Infections

et al. 2021

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“…Numerous genes involved in biofilm formation have been identified in the C. albicans genome, including 50 transcriptional regulatory genes, and 101 transcriptional non-regulatory genes (Shukla and Sobel, 2019). Nobile et al (2012) described the six main transcriptional regulatory genes known as "master" transcriptional regulators, including Efg1 (enhanced filamentous growth), Tec1 (transposon enhancement control), Bcr1 (biofilm and cell wall regulator), Ntd80 (meiosis-specific transcription factor), Brg1 (biofilm regulator), and Rob1 (biofilm regulator).…”

Section: Genomics Of the Biofilmmentioning

confidence: 99%

“…Yeasts that are present in the vagina become pathogenic when the host vagina allows it (Miró et al, 2017). Hostrelated factors involve pregnancy (Brown et al, 2019), hormonal imbalance, ill-treated diabetes, immunosuppression (either through immunosuppressive drugs or infection with the human immunodeficiency virus), which can act as a predisposing factor (Yano et al, 2019), use of broad-spectrum antibiotics (Shukla and Sobel, 2019) and glucocorticoids, and genetic predispositions (Gonçalves et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Pathogenesis and Clinical Relevance of Candida Biofilms in Vulvovaginal Candidiasis

et al. 2020

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The ability of Candida spp. to form biofilms is crucial for its pathogenicity, and thus, it should be considered an important virulence factor in vulvovaginal candidiasis (VVC) and recurrent VVC (RVVC). Its ability to generate biofilms is multifactorial and is generally believed to depend on the site of infection, species and strain involved, and the microenvironment in which the infection develops. Therefore, both cell surface proteins, such as Hwp1, Als1, and Als2, and the cell wall-related protein, Sun41, play a critical role in the adhesion and virulence of the biofilm. Immunological and pharmacological approaches have identified the NLRP3 inflammasome as a crucial molecular factor contributing to host immunopathology. In this context, we have earlier shown that Candida albicans associated with hyphae-secreted aspartyl proteinases (specifically SAP4-6) contribute to the immunopathology of the disease. Transcriptome profiling has revealed that non-coding transcripts regulate protein synthesis post-transcriptionally, which is important for the growth of Candida spp. Other studies have employed RNA sequencing to identify differences in the 1,245 Candida genes involved in surface and invasive cellular metabolism regulation. In vitro systems allow the simultaneous processing of a large number of samples, making them an ideal screening technique for estimating various physicochemical parameters, testing the activity of antimicrobial agents, and analyzing genes involved in biofilm formation and regulation ( in situ ) in specific strains. Murine VVC models are used to study C. albicans infection, especially in trials of novel treatments and to understand the cause(s) for resistance to conventional therapeutics. This review on the clinical relevance of Candida biofilms in VVC focuses on important advances in its genomics, transcriptomics, and proteomics. Moreover, recent experiments on the influence of biofilm formation on VVC or RVVC pathogenesis in laboratory animals have been discussed. A clear elucidation of one of the pathogenesis mechanisms employed by Candida biofilms in vulvovaginal candidiasis and its applications in clinical practice represents the most significant contribution of this manuscript.

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“…This might be due to regular use of TCS among patients, as recent TCS treatment was associated with an increased richness on AD LS. Another possible explanation might be that antibacterial therapy alters the microbiome by reduction of bacteria thereby contributing to proliferation and changed virulence characteristics of the remaining microbes such as fungi, similar to what have previously been described for Candida vaginitis after antibiotic treatment [20].…”

Section: Discussionmentioning

confidence: 77%

Identification of Cutaneous Fungi and Mites in Adult Atopic Dermatitis: Analysis by Targeted 18S rRNA Amplicon Sequencing

Edslev

Andersen

Ingham

et al. 2020

Preprint

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Background: Atopic dermatitis (AD) patients have a changed skin bacterial community, with high abundance of Staphylococcus aureus associated with flairs, highlighting that microbial organisms may be important for disease exacerbation. Despite strong evidence of association between bacterial skin colonization and AD, very limited knowledge regarding the eukaryotic microbial community, including fungi and ectoparasites, in AD exists. In this study, we compared the skin and nasal eukaryotic microbial community between adult AD patients (n=55) and non-AD healthy controls (n=45) using targeted 18S rRNA amplicon sequencing. Analysis was based on the presence or absence of eukaryotic microorganisms. Results: The cutaneous composition of the eukaryotic microbial community and the alpha-diversity differed significantly between AD patients and non-AD individuals, with increased species richness on AD skin. Alpha-diversity and beta-diversity were similar on lesional and non-lesional skin of patients. The ectoparasite Demodex folliculorum and the yeast Geotrichum candidum were significantly more prevalent on the skin of AD patients. The prevalence of D. folliculorum on lesional skin was greater among patients recently treated with topical corticosteroid. Malassezia was one of the most frequently detected genera at all sites, with M. globosa and M. restricta being the most prevalent. M. restricta was overrepresented in the anterior nares of AD patients as compared to the non-AD control population. Conclusion: Significant differences in the eukaryotic microbial communities were found between AD patients and non-AD individuals, with the most striking finding being the significantly overrepresentation of D. folliculorum on AD skin. Whether D. folliculorum can contribute to skin inflammation in AD needs further investigation.

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Vulvovaginitis Caused by Candida Species Following Antibiotic Exposure

Cited by 35 publications

References 28 publications

A Combination of Polybacterial MV140 and Candida albicans V132 as a Potential Novel Trained Immunity-Based Vaccine for Genitourinary Tract Infections

A Combination of Polybacterial MV140 and Candida albicans V132 as a Potential Novel Trained Immunity-Based Vaccine for Genitourinary Tract Infections

Pathogenesis and Clinical Relevance of Candida Biofilms in Vulvovaginal Candidiasis

Identification of Cutaneous Fungi and Mites in Adult Atopic Dermatitis: Analysis by Targeted 18S rRNA Amplicon Sequencing

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