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Focus on Cervicovaginal Health: Microbiome, Sexually Transmitted Infections, and Beneficial Microbes

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A special issue of Pathogens (ISSN 2076-0817). This special issue belongs to the section "Epidemiology of Infectious Diseases".

Deadline for manuscript submissions: closed (15 January 2024) | Viewed by 15563

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Special Issue Editors

Dr. Antonella Marangoni

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Department of Experimental, Diagnostic and Specialty Medicine—DIMES, University of Bologna, Bologna 40138, Italy
Interests: genital microbiota and interactions between health promoting bacteria (as lactobacilli) and pathogens; laboratory diagnosis of sexually transmitted diseases and maternal-foetal infections; epidemiology of the main bacterial sexually transmitted infections; role of Chlamydia pneumoniae infection in inducing a dyslipidemic effect in experimental models
Special Issues, Collections and Topics in MDPI journals

Dr. Claudio Foschi

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Guest Editor

Department of Experimental, Diagnostic and Specialty Medicine—DIMES, University of Bologna, Bologna 40138, Italy
Interests: bacterial sexually transmitted infections; Chlamydia trachomatis; vaginal microbiome; lactobacilli; host-pathogen interactions; metabolomics
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The cervicovaginal ecosystem is made up of diverse microorganisms coexisting in a dynamic balance and establishing complex connections with each other and with the host. In healthy reproductive-aged women, the vaginal microbiome generally shows a predominance of lactobacilli. Lactobacilli promote the maintenance of the vaginal homeostasis and prevent the colonization and growth of adverse microorganisms (e.g., Candida spp., anaerobes associated with bacterial vaginosis), including those responsible for sexually transmitted infections (e.g., Chlamydia trachomatis, Neisseria gonorrhoeae). Such defensive function is exerted through various mechanisms, such as vaginal pH lowering, bioactive compound production, competition for nutrients and adhesion sites, and modulation of the host immune response. However, the composition of the vaginal microbiome can vary throughout a woman’s life in response to endogenous and exogenous factors, such as age, pregnancy, pharmaceutical treatments, and urogenital infections.

Understanding the pathophysiology of the vaginal microbiota is crucial for maintaining the health and functioning of the female genital tract, in terms of novel biomarker discovery and development of new therapeutic approaches.

This Special Issue will cover a wide range of topics focusing on vaginal health: composition and functioning of the cervicovaginal microbiome in normal and pathological conditions, interactions between ‘health-promoting’ microorganisms and urogenital pathogens, discovery of new vaginal biomarkers in healthy status and dysbiosis, epidemiology and risk factors of common genital disorders (bacterial vaginosis, STIs, vulvovaginal candidiasis), animal models on the vaginal microenvironment, and innovative antimicrobial-free treatments for urogenital infections.

This Special issue aims to help to enhance current knowledge on the role and functioning and of the cervicovaginal microbial niche. All types of articles will be considered for publication, including short reports, primary research articles, and reviews.

We look forward to your contribution.

Dr. Antonella Marangoni
Dr. Claudio Foschi
Guest Editors

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pathogens is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

vaginal microbiome
vaginal metabolome
lactobacilli
host–pathogen interactions
sexually transmitted infections
Chlamydia
gonorrhea
vaginal dysbiosis
vulvovaginal candidiasis
animal models

Published Papers (7 papers)

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Research

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16 pages, 717 KiB

Open AccessEditor’s ChoiceArticle

Cervical HPV Infections, Sexually Transmitted Bacterial Pathogens and Cytology Findings—A Molecular Epidemiology Study

by George Valasoulis, Abraham Pouliakis, Georgios Michail, Ioulia Magaliou, Christos Parthenis, Niki Margari, Christine Kottaridi, Aris Spathis, Danai Leventakou, Argyro-Ioanna Ieronimaki, Georgios Androutsopoulos, Periklis Panagopoulos, Alexandros Daponte, Sotirios Tsiodras and Ioannis G. Panayiotides

Pathogens 2023, 12(11), 1347; https://doi.org/10.3390/pathogens12111347 - 14 Nov 2023

Cited by 1 | Viewed by 1157

Abstract

Prevalent cervical HPV infection and high-risk HPV persistence consequences have been extensively investigated in the literature; nevertheless, any causative interrelations of other sexually transmitted bacterial infections (STIs) with cervical HPV infection have not yet been fully elucidated. This study aimed to investigate the possible association of STIs with cervical cytology aberrations and HPV genotyping results in a representative sample of predominantly young Greek women. Liquid-based cytology and molecular detection for bacterial STIs and HPV as well as extended HPV genotyping were simultaneously assessed in cervical samples from 2256 individuals visiting several urban outpatient Gynecology Departments for well-woman visits or cervical screening throughout a 20-month period. All specimens were centrally processed with validated molecular assays. The mean age of the studied women was 37.0 ± 11.7 years; 722 women (33.30%) tested positive for STI (mean age 34.23 ± 10.87 years). A higher mean age (38.34 ± 11.83 years (p < 0.05)) was associated with negative STI testing. Chlamydia trachomatis was detected in 59 individuals (8.2%), Mycoplasma hominis in 156 (21.6%), Mycoplasma genitalium in 14 (1.9%), and Ureaplasma spp. in 555 (76.9%); infections with two bacterial pathogens were identified in 73 samples (10.1%). Cervical HPV was detected in 357 out of 1385 samples with a valid HPV typing result (25.8%). The mean age of HPV-positive women was 32.0 ± 8.4 years; individuals testing HPV-negative were slightly older (N = 1028): 34.4 ± 9.2 (p < 0.05). Among the 1371 individuals with valid results both for bacterial STIs and cervical HPV detection, women with an HPV-positive sample were more likely to harbor an STI (OR: 2.69, 95% CI 2.10–3.46, p < 0.05). Interestingly, bacterial STI positivity illustrated significant heterogeneity between NILM and LSIL cases, with 28.88% of NILM and 46.33% of LSIL cases harboring an STI, respectively (p < 0.05). In brief, in a population with a high prevalence for STIs, especially Ureaplasma spp., an association was documented between bacterial pathogen detection and cervical HPV infection, as well as abnormal cytology; these findings merit further investigation. Full article

(This article belongs to the Special Issue Focus on Cervicovaginal Health: Microbiome, Sexually Transmitted Infections, and Beneficial Microbes)

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17 pages, 16314 KiB

Open AccessArticle

In Vitro Analysis of Matched Isolates from Localized and Disseminated Gonococcal Infections Suggests That Opa Expression Impacts Clinical Outcome

by Cheng-Tai Wu, Po-Wei Huang, Chia-Hsuan Lin, Daniel C. Stein, Wenxia Song, Sung-Pin Tseng and Liang-Chun Wang

Pathogens 2022, 11(2), 217; https://doi.org/10.3390/pathogens11020217 - 7 Feb 2022

Cited by 3 | Viewed by 1858

Abstract

Gonorrhea is the second most common sexually transmitted infection, which is primarily localized but can be disseminated systemically. The mechanisms by which a localized infection becomes a disseminated infection are unknown. We used five pairs of Neisseria gonorrhoeae isolates from the cervix/urethra (localized) and the blood (disseminated) of patients with disseminated gonococcal infection to examine the mechanisms that confine gonococci to the genital tract or enable them to disseminate to the blood. Multilocus sequence analysis found that the local and disseminated isolates from the same patients were isogenic. When culturing in vitro, disseminated isolates aggregated significantly less and transmigrated across a polarized epithelial monolayer more efficiently than localized isolates. While localized cervical isolates transmigrated across epithelial monolayers inefficiently, those transmigrated bacteria self-aggregated less and transmigrated more than cervical isolates but comparably to disseminating isolates. The local cervical isolates recruited the host receptors of gonococcal Opa proteins carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) on epithelial cells. However, the transmigrated cervical isolate and the disseminated blood isolates recruit CEACAMs significantly less often. Our results collectively suggest that switching off the expression of CEACAM-binding Opa(s), which reduces self-aggregation, promotes gonococcal dissemination. Full article

(This article belongs to the Special Issue Focus on Cervicovaginal Health: Microbiome, Sexually Transmitted Infections, and Beneficial Microbes)

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14 pages, 1305 KiB

Open AccessArticle

Monitoring Sexually Transmitted Infections in Cervicovaginal Exfoliative Samples in Mexican Women

by Fabiola Hernández-Rosas, Manuel Rey-Barrera, Ulises Conejo-Saucedo, Erika Orozco-Hernández, Liliana Maza-Sánchez, Enrique Navarro-Vidal, Yasmín López-Vera, María del Carmen Ascencio-Gordillo and Mercedes Piedad de León-Bautista

Pathogens 2021, 10(12), 1618; https://doi.org/10.3390/pathogens10121618 - 13 Dec 2021

Cited by 2 | Viewed by 2209

Abstract

Background. Globally, Sexually Transmitted Infections (STIs) are a major cause of morbidity in sexually active individuals, having complications in reproduction health and quality of life. In concordance with the Sustainable Development Goals (SDG), the study aimed to investigate the prevalence of Candida spp., Ureaplasma spp., Trichomonas vaginalis, Neisseria gonorrhoeae, Chlamydia trachomatis, HSV, and Mycoplasma spp. from cervicovaginal samples and to correlate them with the gynecological history of the patients. Methods. Our analytical, prospective, and cross-sectional study included 377 women who participated in a reproductive health campaign during 2015–2016. Anthropometric and gynecological variables were obtained. Cervicovaginal specimens were collected and analyzed with a multiplex in-house PCR to detect Candida spp., Ureaplasma spp., Trichomonas vaginalis, Neisseria gonorrhoeae, HSV, Mycoplasma spp., and Chlamydia trachomatis. Results. The positive cases were 175/377 (46.4%) to at least one of the microorganisms. The most frequent pathogen detected in this population was Ureaplasma spp. (n = 111, 29.4%), followed by Mycoplasma spp. (n = 56, 14.9%) and Candida spp. (n = 47, 12.5%); 33.7% of the positive cases were single infections, whereas 12.7% had coinfection. The multiplex PCR assay was designed targeting nucleotide sequences. Conclusions. Our data demonstrated that monitoring STIs among asymptomatic patients will encourage target programs to be more precisely and effectively implemented, as well as make these programs more affordable, to benefit society by decreasing the prevalence of STIs. Full article

(This article belongs to the Special Issue Focus on Cervicovaginal Health: Microbiome, Sexually Transmitted Infections, and Beneficial Microbes)

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15 pages, 2064 KiB

Open AccessArticle

Antimicrobial Activity of a Vaginal Gel Formulation: Considerations Related to Vaginal Infection and Dysbiosis

by Francesco De Seta and Bryan Larsen

Pathogens 2021, 10(12), 1576; https://doi.org/10.3390/pathogens10121576 - 3 Dec 2021

Cited by 2 | Viewed by 3050

Abstract

Many non-prescription preparations intended to treat or alleviate symptoms of vaginal infection are available in American and European markets, but many have scant preclinical or clinical research underpinning. Respecta^®Balance Gel (RBG) is marketed as an adjunct to probiotic treatment and its relevant antimicrobial properties were studied. Key findings with the manufacturer-supplied gel showed reduced turbidity in broth-dilution tests by 50% against Candida albicans and Candida glabrata at RBG concentrations 0.2–0.4% of neat product, respectively. A 50% reduction in turbidity of Escherichia coli, Streptococcus agalactiae, Enterococcus faecalis ranged from 1.6–2.2% and Gardnerella vaginalis was shown by flow cytometry counts to undergo a 50% reduction at 0.3% RBG. Propidium iodide staining indicated a rapid reduction of cell integrity of G. vaginalis almost immediately while after 4 h 45% of E. coli cells were stained. The lactic acid in BHI inhibited bacteria and yeast at concentrations ranging from 0.2–1.8% but inhibition was not solely due to pH since a 1:4 dilution of RBG resulted in a pH near neutral (6.75). Other findings showed biofilm accumulation assessed after 10-days exposure of Candida spp. to RBG and was reduced by an average of one-third (community strains) to one-half (drug-resistant strains). One excipient of the RBG, disodium EDTA, inhibited the growth of bacteria and yeast at concentrations below those present in RBG and may accentuate the activity of the host defense factor, lactoferrin. We conclude that RBG is a potent inhibitor of vaginal microorganisms relevant to vaginitis or intrapartum infections and contains excipients that may contribute to its antimicrobial activity. Full article

(This article belongs to the Special Issue Focus on Cervicovaginal Health: Microbiome, Sexually Transmitted Infections, and Beneficial Microbes)

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14 pages, 1930 KiB

Open AccessArticle

Distribution of ermB, ermF, tet(W), and tet(M) Resistance Genes in the Vaginal Ecosystem of Women during Pregnancy and Puerperium

by Marco Severgnini, Tania Camboni, Camilla Ceccarani, Sara Morselli, Alessia Cantiani, Sara Zagonari, Giulia Patuelli, Maria Federica Pedna, Vittorio Sambri, Claudio Foschi, Clarissa Consolandi and Antonella Marangoni

Pathogens 2021, 10(12), 1546; https://doi.org/10.3390/pathogens10121546 - 26 Nov 2021

Cited by 9 | Viewed by 2032

Abstract

The inhabitants of the vaginal ecosystem can harbor genetic determinants conferring antimicrobial resistance. However, detailed data about the distribution of resistance genes in the vaginal microbiome of pregnant women are still lacking. Therefore, we assessed the presence of macrolide (i.e., erm genes) and tetracycline (i.e., tet genes) resistance markers in the vaginal environment of Caucasian women at different gestational ages. Furthermore, the detection of resistance genes was related to the composition of the vaginal microbiota. A total of 228 vaginal samples, collected at different trimesters of pregnancy or during the puerperium, were tested for the presence of ermB, ermF, tet(W), and tet(M) by in-house end-point PCR assays. The composition of the vaginal microbiota was assessed through a microscopic evaluation (i.e., Nugent score) and by means of sequencing V3–V4 hypervariable regions of the bacterial 16 rRNA gene. Overall, the most detected resistance gene was tet(M) (76.7%), followed by ermB (55.2%). In 17% of women, mainly with a ‘normal’ vaginal microbiota, no resistance genes were found. Except for tet(W), a significant correlation between the positivity of resistance genes and a dysbiotic vaginal status (i.e., bacterial vaginosis (BV)) was noticed. Indeed, samples positive for at least one resistance determinant were characterized by a decrease in Lactobacillus spp. and an increase of BV-related genera (Prevotella, Gardnerella, Atopobium, Sneathia). A high predominance of vaginal Lactobacillus spp. (>85%) was associated with a lower risk of tet(W) gene detection, whereas the presence of Megasphaera (>1%) increased the risk of positivity for all analyzed genes. Different types of vaginal microbiota are associated with peculiar resistance profiles, being a lactobacilli-dominated ecosystem poor in or free of resistance genes. These data could open new perspectives for promoting maternal and neonatal health. Full article

(This article belongs to the Special Issue Focus on Cervicovaginal Health: Microbiome, Sexually Transmitted Infections, and Beneficial Microbes)

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15 pages, 2786 KiB

Open AccessArticle

Vaginal and Anal Microbiome during Chlamydia trachomatis Infections

by Stefano Raimondi, Francesco Candeliere, Alberto Amaretti, Claudio Foschi, Sara Morselli, Valeria Gaspari, Maddalena Rossi and Antonella Marangoni

Pathogens 2021, 10(10), 1347; https://doi.org/10.3390/pathogens10101347 - 19 Oct 2021

Cited by 11 | Viewed by 2744

Abstract

Background.Chlamydia trachomatis (CT) is the agent of the most common bacterial sexually transmitted infection worldwide, with a significant impact on women’s health. Despite the increasing number of studies about the vaginal microbiome in women with CT infections, information about the composition of the anal microbiome is still lacking. Here, we assessed the bacterial community profiles of vaginal and anal ecosystems associated or not with CT infection in a cohort of Caucasian young women. Methods. A total of 26 women, including 10 with a contemporary vaginal and ano-rectal CT infection, were enrolled. Composition of vaginal and anal microbiome was studied by 16S rRNA gene profiling. Co-occurrence networks of bacterial communities and metagenome metabolic functions were determined. Results. In case of CT infection, both vaginal and anal environments were characterized by a degree of dysbiosis. Indeed, the vaginal microbiome of CT-positive women were depleted in lactobacilli, with a significant increase in dysbiosis-associated bacteria (e.g., Sneathia, Parvimonas, Megasphaera), whereas the anal microbiota of CT-infected women was characterized by higher levels of Parvimonas and Pseudomonas and lower levels of Escherichia. Interestingly, the microbiome of anus and vagina had numerous bacterial taxa in common, reflecting a significant microbial ‘sharing’ between the two sites. In the vaginal environment, CT positively correlated with Ezakiella spp. while Gardnerella vaginalis co-occurred with several dysbiosis-related microbes, regardless of CT vaginal infection. The vaginal microbiome of CT-positive females exhibited a higher involvement of chorismate and aromatic amino acid biosynthesis, as well as an increase in mixed acid fermentation. Conclusions. These data could be useful to set up new diagnostic/prognostic tools, offering new perspectives for the control of chlamydial infections. Full article

(This article belongs to the Special Issue Focus on Cervicovaginal Health: Microbiome, Sexually Transmitted Infections, and Beneficial Microbes)

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10 pages, 569 KiB

Open AccessBrief Report

HTLV-1 Proviral Load in Vaginal Fluid Correlates with Levels in Peripheral Blood Mononuclear Cells

by Alisson de Aquino Firmino, Paulo Roberto Tavares Gomes Filho, Adenilda Lima Lopes Martins, Thessika Hialla Araújo, Luana Leandro Gois, Everton da Silva Batista, Jean Paulo Lacerda Araújo, Bernardo Galvão-Castro and Maria Fernanda Rios Grassi

Pathogens 2023, 12(5), 682; https://doi.org/10.3390/pathogens12050682 - 5 May 2023

Cited by 1 | Viewed by 1488

Abstract

Background: The prevalence of human T-lymphotropic virus type-1 (HTLV-1) infection is higher in women, and sexual intercourse has been described as an important route of male-to-female transmission. The present study aimed to quantify HTLV-1 proviral load (PVL) in vaginal fluid, and to investigate correlations with PVL in peripheral blood mononuclear cells (PBMCs). In addition, cytopathological alterations and vaginal microbiota were evaluated. Methods: HTLV-1-infected women were consecutively recruited at a multidisciplinary center for HTLV patients in Salvador, Brazil. All women underwent gynecological examinations to obtain cervicovaginal fluid and venipuncture for blood collection. PVL, as measured by real-time quantitative polymerase chain reaction (RT–qPCR), was expressed as the number of copies of HTLV-1/10⁶ cells in blood and vaginal fluid samples. Light microscopy was used to assess cervicovaginal cytopathology and vaginal microbiota. Results: In the 56 included women (43 asymptomatic carriers and 13 diagnosed with HTLV-1-associated myelopathy/tropical spastic paraparesis—HAM/TSP), mean age was 35.9 (SD ± 7.2) years. PVL was higher in PBMCs (median: 23,264 copies/10⁶ cells; IQR: 6776–60,036) than in vaginal fluid (451.9 copies/10⁶ cells; IQR: 0–2490) (p < 0.0001). PVL in PBMCs was observed to correlate directly with PVL in vaginal fluid (R = 0.37, p = 0.006). PVL was detected in the vaginal fluid of 24 of 43 (55.8%) asymptomatic women compared to 12 of 13 (92.3%) HAM/TSP patients, p = 0.02. Cytopathologic analyses revealed no differences between women with detectable or undetectable PVL. Conclusion: HTLV-1 proviral load is detectable in vaginal fluid and correlates directly with proviral load in peripheral blood. This finding suggests that sexual transmission of HTLV-1 from females to males may occur, as well as vertical transmission, particularly in the context of vaginal delivery. Full article

(This article belongs to the Special Issue Focus on Cervicovaginal Health: Microbiome, Sexually Transmitted Infections, and Beneficial Microbes)

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