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1.
PLoS One ; 16(1): e0245937, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33481958

RESUMO

OBJECTIVE: To determine the association between microbial invasion of the amniotic cavity (MIAC) and/or intra-amniotic inflammation (IAI) and the cervical prevalence of Gardnerella vaginalis DNA in pregnancies with preterm prelabor rupture of membrane (PPROM). METHOD: In total, 405 women with singleton pregnancies complicated with PPROM were included. Cervical fluid and amniotic fluid samples were collected at the time of admission. Bacterial and G. vaginalis DNA were assessed in the cervical fluid samples using quantitative PCR technique. Concentrations of interleukin-6 and MIAC were evaluated in the amniotic fluid samples. Loads of G. vaginalis DNA ≥ 1% of the total cervical bacterial DNA were used to define the cervical prevalence of G. vaginalis as abundant. Based on the MIAC and IAI, women were categorized into four groups: with intra-amniotic infection (both MIAC and IAI), with sterile IAI (IAI without MIAC), with MIAC without IAI, and without either MIAC or IAI. RESULTS: The presence of the abundant cervical G. vaginalis was related to MIAC (with: 65% vs. without: 44%; p = 0.0004) but not IAI (with: 52% vs. without: 48%; p = 0.70). Women with MIAC without IAI had the highest load of the cervical G. vaginalis DNA (median 2.0 × 104 copies DNA/mL) and the highest presence of abundant cervical G. vaginalis (73%). CONCLUSIONS: In women with PPROM, the presence of cervical G. vaginalis was associated with MIAC, mainly without the concurrent presence of IAI.


Assuntos
Líquido Amniótico/microbiologia , Colo do Útero/microbiologia , Ruptura Prematura de Membranas Fetais/microbiologia , Gardnerella vaginalis/isolamento & purificação , Adulto , Líquido Amniótico/química , Corioamnionite/microbiologia , Feminino , Humanos , Interleucina-6/análise , Gravidez , Estudos Prospectivos
2.
Trop Anim Health Prod ; 53(1): 132, 2021 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-33469798

RESUMO

Vaginal and cervical adhesions are severe long-standing reproductive disorder in dromedaries and consequently result in a high culling rate. This study was designed to compare the microbial communities of the vaginae, cervices, and uteri of normal (n = 10) camels versus camels suffering from cervico-vaginal adhesion (n = 23). Vaginal, cervical, and uterine swab samples were collected from control and affected animals. Furthermore, serum samples were obtained for serological testing of Chlamydiosis and Coxiellosis. For bacteriological and fungal examination, swab samples were plated on Columbia and Saboraud's dextrose agar, respectively. Polymerase chain reaction (PCR) assay was applied to samples expressed seropositive for Chlamydiosis. Vaginal swab bacterial cultures showed that the affected animals were significantly infected with Staphylococcus aureus (P = 0.0322, CI: 0.25-0.95) than the control, while mycological cultures showed that both control and affected animals were infected with Cryptococcus and Candida albicans. Corynebacterium spp. (22.7%), Pseudomonas spp. (4.5%), Klebsiella spp. (9.1%), T. pyogenes (18.2%), and anaerobic bacteria (Fusobacterium necrophorum and Clostridium spp.; 34.78%) were also identified in affected animals. Cervical samples from affected animals were distinguished by the existence of S. aureus (27.8%), Klebsiella spp. (5.6%), Corynebacterium spp. (22.2%), Cryptococcus (16.7%), Proteus spp. (11.1% (, T. pyogenes (11.1%), Pseudomonas spp. (5.6%), and Fusobacterium necrophorum (17.4%). Uterine samples from affected animals were characterized by the presence of S. aureus (22.2%), Streptococcus (22.2%), Corynebacterium spp. (11.1%), E. coli (11.1%), and Pseudomonas spp. (11.1%). Anaerobic bacteria were not isolated from control nor affected animals. Enzyme immunoassays revealed that 50% and 34.8% of the control and affected animals were positive for Coxiella burnetii, respectively, Chlamydia was detected in 43.5% of samples from affected animals, only 60% of which were confirmed positive. These results show that microbial communities linked with cervico-vaginal adhesion in dromedary camels are likely to be polymicrobial. The findings of this study are helpful in designing antimicrobial therapies toward reducing the incidence for cervico-vaginal adhesion.


Assuntos
Camelus/microbiologia , Colo do Útero/microbiologia , Aderências Teciduais/veterinária , Útero/microbiologia , Vagina/microbiologia , Animais , Bactérias/classificação , Feminino , Aderências Teciduais/microbiologia
3.
Nat Commun ; 11(1): 4126, 2020 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-32807804

RESUMO

Neisseria gonorrhoeae is an urgent public health threat due to rapidly increasing incidence and antibiotic resistance. In contrast with the trend of increasing resistance, clinical isolates that have reverted to susceptibility regularly appear, prompting questions about which pressures compete with antibiotics to shape gonococcal evolution. Here, we used genome-wide association to identify loss-of-function (LOF) mutations in the efflux pump mtrCDE operon as a mechanism of increased antibiotic susceptibility and demonstrate that these mutations are overrepresented in cervical relative to urethral isolates. This enrichment holds true for LOF mutations in another efflux pump, farAB, and in urogenitally-adapted versus typical N. meningitidis, providing evidence for a model in which expression of these pumps in the female urogenital tract incurs a fitness cost for pathogenic Neisseria. Overall, our findings highlight the impact of integrating microbial population genomics with host metadata and demonstrate how host environmental pressures can lead to increased antibiotic susceptibility.


Assuntos
Proteínas de Bactérias/metabolismo , Colo do Útero/microbiologia , Neisseria gonorrhoeae/efeitos dos fármacos , Neisseria gonorrhoeae/genética , Animais , Proteínas de Bactérias/genética , Resistência Microbiana a Medicamentos/genética , Feminino , Regulação Bacteriana da Expressão Gênica , Estudo de Associação Genômica Ampla , Humanos , Testes de Sensibilidade Microbiana , Mutação/genética , Neisseria gonorrhoeae/metabolismo , Óperon/genética , Regiões Promotoras Genéticas/genética
4.
PLoS One ; 15(6): e0234730, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32569308

RESUMO

The pathogenicity of Escherichia coli strains that cause cervico-vaginal infections (CVI) is due to the presence of several virulence genes. The objective of this study was to define the variability regarding the genotype of antibiotic resistance, the transcription profiles of virulence genes after in vitro infection of the vaginal cell line A431 and the phylogroup composition of a group of cervico-vaginal E. coli strains (CVEC). A total of 200 E. coli strains isolated from Mexican women with CVI from two medical units of the Mexican Institute of Social Security were analysed. E. coli strains and antibiotic resistance genes were identified using conventional polymerase chain reaction (PCR), and phylogroups were identified using multiplex PCR. Virulence gene transcription was measured through reverse-transcriptase real-time PCR after infection of the vaginal cell line A431. The most common antibiotic resistance genes among the CVEC strains were aac(3)II, TEM, dfrA1, sul1, and qnrA. The predominant phylogroup was B2. The genes most frequently transcribed in these strains were fimH, papC, irp2, iroN, kpsMTII, cnf1, and ompT, mainly in CVEC strains isolated from chronic and occasional vaginal infections. The strains showed a large diversity of transcription of the virulence genes phenotype and antibiotic resistance genotype, especially in the strains of phylogroups, B2, A, and D. The strains formed 2 large clusters, which contained several subclusters. The genetic diversity of CVEC strains was high. These strains have a large number of transcription patterns of virulence genes, and one-third of them carry three to seven antibiotic resistance genes.


Assuntos
Colo do Útero/microbiologia , Resistência Microbiana a Medicamentos , Escherichia coli/genética , Escherichia coli/patogenicidade , Filogenia , Transcrição Genética/efeitos dos fármacos , Vagina/microbiologia , Escherichia coli/efeitos dos fármacos , Feminino , Humanos , México , Virulência/genética
5.
BMC Infect Dis ; 20(1): 375, 2020 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-32460721

RESUMO

BACKGROUND: Sexually transmitted infections (STIs) cause a major public health problem that affect both men and women in developing and developed countries. The aim of the study was to estimate the prevalence of 11 STIs among women who voluntarily participated in the study, while seeking gynecological checkup. The existence of an association between the presence of pathogens and symptoms and various sociodemographic risk factors was assessed. METHODS: A total of 505 vaginal and cervical specimens were collected from women above 18 years of age, with or without symptoms related to gynecological infections. Nucleic acid was extracted and samples were tested by real-time PCR for the following pathogens: Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma genitalium, Ureaplasma urealyticum, Urealplasma parvum, Trichomonas vaginalis, Mycoplasma hominis, Mycoplasma girerdii, Gardnerella vaginalis, Candida albicans and Human Papillomavirus (HPV). Positive HPV samples underwent genotyping using a microarray system. RESULTS: Of the 505 samples, 312 (62%) were screened positive for at least one pathogen. Of these, 36% were positive for Gardnerella vaginalis, 35% for Ureaplasma parvum, 8% for Candida albicans, 6.7% for HPV, 4.6% for Ureaplasma urealyticum, 3.6% for Mycoplasma hominis, 2% for Trichomonas vaginalis, 0.8% for Chlamydia trachomatis, 0.4% for Mycoplasma girerdii, 0.2% for Mycoplasma genitalium and 0.2% for Neisseria gonorrhoeae. Lack of symptoms was reported in 187 women (37%), among whom 61% were infected. Thirty-four samples were HPV positive, with 17 high risk HPV genotypes (HR-HPV); the highest rates being recorded for types 16 (38%), 18 (21%) and 51 (18%). Out of the 34 HPV positives, 29 participants had HR-HPV. Association with various risk factors were reported. CONCLUSIONS: This is the first study that presents data about the presence of STIs among women in Lebanon and the MENA region by simultaneous detection of 11 pathogens. In the absence of systematic STI surveillance in Lebanon, concurrent screening for HPV and PAP smear is warranted.


Assuntos
Doenças Sexualmente Transmissíveis/epidemiologia , Adulto , Colo do Útero/microbiologia , Colo do Útero/parasitologia , Colo do Útero/virologia , Chlamydia trachomatis/genética , Chlamydia trachomatis/isolamento & purificação , Estudos Transversais , Feminino , Gardnerella vaginalis/genética , Gardnerella vaginalis/isolamento & purificação , Humanos , Líbano/epidemiologia , Masculino , Epidemiologia Molecular , Infecções por Mycoplasma/epidemiologia , Mycoplasma genitalium/genética , Mycoplasma genitalium/isolamento & purificação , Mycoplasma hominis/genética , Mycoplasma hominis/isolamento & purificação , Neisseria gonorrhoeae/genética , Neisseria gonorrhoeae/isolamento & purificação , Papillomaviridae/genética , Papillomaviridae/isolamento & purificação , Fatores de Risco , Doenças Sexualmente Transmissíveis/microbiologia , Doenças Sexualmente Transmissíveis/parasitologia , Doenças Sexualmente Transmissíveis/virologia , Trichomonas vaginalis/genética , Trichomonas vaginalis/isolamento & purificação , Ureaplasma/genética , Ureaplasma/isolamento & purificação , Vagina/microbiologia , Vagina/parasitologia , Vagina/virologia , Esfregaço Vaginal , Adulto Jovem
6.
Sci Rep ; 10(1): 8514, 2020 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-32444843

RESUMO

The immunology and microbiota of the female genital tract (FGT) are key determinants of HIV susceptibility. Cervical cytobrush sampling is a relatively non-invasive method permitting the longitudinal assessment of endocervical immune cells, but effects on FGT immunology are unknown. Blood, cervico-vaginal secretions and cervical cytobrushes were collected from sexually transmitted infection (STI)-free women at baseline and after either 6 hours or 48 hours. Endocervical immune cell subsets were assessed by flow cytometry, and pro-inflammatory cytokines by multiplex ELISA. The density of Lactobacillus species and key bacterial vaginosis-associated bacterial taxa were determined by qPCR. Paired changes were assessed before and after cytobrush sampling. After 6 hours there were significant increases in CD4 + T cell, antigen presenting cell (APC) and neutrophil numbers; APC elevations persisted at 48 hours, while neutrophil and CD4 + T cell numbers returned to baseline. In addition, pro-inflammatory cytokine levels were increased at 6 hours and returned to baseline by 48 hours. No significant changes were observed in the absolute abundance of Lactobacillus species or BV-associated bacteria at either time point. Overall, cytobrush sampling altered genital immune parameters at 6 hours, but only APC number increases persisted at 48 hours. This should be considered in longitudinal analyses of FGT immunology.


Assuntos
Colo do Útero/imunologia , Infecções por HIV/epidemiologia , HIV/isolamento & purificação , Microbiota/imunologia , Manejo de Espécimes/métodos , Vagina/imunologia , Vaginose Bacteriana/imunologia , Adolescente , Adulto , Canadá/epidemiologia , Colo do Útero/microbiologia , Colo do Útero/virologia , Citocinas/análise , Citocinas/imunologia , Feminino , Infecções por HIV/diagnóstico , Infecções por HIV/etiologia , Humanos , Estudos Prospectivos , Vagina/microbiologia , Vagina/virologia , Vaginose Bacteriana/microbiologia , Vaginose Bacteriana/virologia , Carga Viral , Adulto Jovem
7.
Adv Exp Med Biol ; 1219: 77-91, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32130694

RESUMO

Several aspects of the human physiology are controlled by the microbiota that plays a key role in health and disease. In fact, microbial dysbiosis is associated with numerous diseases, including several types of cancer such as colon, gastric, esophageal, pancreatic, laryngeal, breast and gallbladder carcinomas.Metabolic symbiosis between non-malignant cells and the resident microbita is crucial for the host homeostasis. However, cancer cells are able to repurpose the pre-existing metabolic symbiosis, being able to recycle those relations and also create novel metabolic symbiosis, leading to profound alterations on the local microenvironment.In here we will explore some of these symbiotic metabolic interactions between bacteria and non-malignant cells in two different contexts: colon and uterine cervix. The way malignant cells are able to recycle these normal interactions and also create novel types of symbiotic metabolic relations will also be discussed.The knowledge of these complex interactions and recycling mechanisms is of extreme importance for cancer treatment, as new therapeutic targets could be developed.


Assuntos
Bactérias/metabolismo , Células Epiteliais/metabolismo , Neoplasias/metabolismo , Neoplasias/microbiologia , Simbiose , Colo do Útero/citologia , Colo do Útero/metabolismo , Colo do Útero/microbiologia , Colo/citologia , Colo/metabolismo , Colo/microbiologia , Feminino , Humanos , Microbiota/fisiologia
8.
PLoS Pathog ; 16(3): e1008376, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32214382

RESUMO

BACKGROUND: Human papillomavirus (HPV) infection is one of the most common sexually transmitted infections. However, only a small percentage of high-risk (HR) HPV infections progress to cervical precancer and cancer. In this study, we investigated the role of the cervicovaginal microbiome (CVM) in the natural history of HR-HPV. METHODS: This study was nested within the placebo arm of the Costa Rica HPV Vaccine Trial that included women aged 18-25 years of age. Cervical samples from two visits of women with an incident HR-HPV infection (n = 273 women) were used to evaluate the prospective role of the CVM on the natural history of HR-HPV. We focus specifically on infection clearance, persistence, and progression to cervical intraepithelial neoplasia grade 2 and 3 (CIN2+). The CVM was characterized by amplification and sequencing the bacterial 16S V4 rRNA gene region and the fungal ITS1 region using an Illumina MiSeq platform. OTU clustering was performed using QIIME2. Functional groups were imputed using PICRUSt and statistical analyses were performed using R. RESULTS: At Visit 1 (V1) abundance of Lactobacillus iners was associated with clearance of incident HR-HPV infections (Linear Discriminant Analysis (LDA)>4.0), whereas V1 Gardnerella was the dominant biomarker for HR-HPV progression (LDA>4.0). At visit 2 (V2), increased microbial Shannon diversity was significantly associated with progression to CIN2+ (p = 0.027). Multivariate mediation analysis revealed that the positive association of V1 Gardnerella with CIN2+ progression was due to the increased cervicovaginal diversity at V2 (p = 0.040). A full multivariate model of key components of the CVM showed significant protective effects via V1 genus Lactobacillus, OR = 0.41 (0.22-0.79), V1 fungal diversity, OR = 0.90 (0.82-1.00) and V1 functional Cell Motility pathway, OR = 0.75 (0.62-0.92), whereas V2 bacterial diversity, OR = 1.19 (1.03-1.38) was shown to be predictive of progression to CIN2+. CONCLUSION: This study demonstrates that features of the cervicovaginal microbiome are associated with HR-HPV progression in a prospective longitudinal cohort. The analyses indicated that the association of Gardnerella and progression to CIN2+ may actually be mediated by subsequent elevation of microbial diversity. Identified features of the microbiome associated with HR-HPV progression may be targets for therapeutic manipulation to prevent CIN2+. TRIAL REGISTRATION: ClinicalTrials.gov NCT00128661.


Assuntos
Neoplasia Intraepitelial Cervical , Colo do Útero , Gardnerella , Lactobacillus , Microbiota , Papillomaviridae/metabolismo , Infecções por Papillomavirus , Neoplasias do Colo do Útero , Vagina , Adolescente , Adulto , Neoplasia Intraepitelial Cervical/metabolismo , Neoplasia Intraepitelial Cervical/microbiologia , Neoplasia Intraepitelial Cervical/patologia , Neoplasia Intraepitelial Cervical/virologia , Colo do Útero/metabolismo , Colo do Útero/microbiologia , Colo do Útero/patologia , Colo do Útero/virologia , Feminino , Gardnerella/classificação , Gardnerella/genética , Gardnerella/metabolismo , Humanos , Lactobacillus/classificação , Lactobacillus/genética , Lactobacillus/metabolismo , Estudos Longitudinais , Infecções por Papillomavirus/metabolismo , Infecções por Papillomavirus/microbiologia , Infecções por Papillomavirus/patologia , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/microbiologia , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia , Vagina/metabolismo , Vagina/microbiologia , Vagina/patologia , Vagina/virologia
9.
Nat Rev Urol ; 17(4): 232-250, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32071434

RESUMO

The female reproductive tract (FRT), similar to other mucosal sites, harbours a site-specific microbiome, which has an essential role in maintaining health and homeostasis. In the majority of women of reproductive age, the microbiota of the lower FRT (vagina and cervix) microenvironment is dominated by Lactobacillus species, which benefit the host through symbiotic relationships. By contrast, the upper FRT (uterus, Fallopian tubes and ovaries) might be sterile in healthy individuals or contain a low-biomass microbiome with a diverse mixture of microorganisms. When dysbiosis occurs, altered immune and metabolic signalling can affect hallmarks of cancer, including chronic inflammation, epithelial barrier breach, changes in cellular proliferation and apoptosis, genome instability, angiogenesis and metabolic dysregulation. These pathophysiological changes might lead to gynaecological cancer. Emerging evidence shows that genital dysbiosis and/or specific bacteria might have an active role in the development and/or progression and metastasis of gynaecological malignancies, such as cervical, endometrial and ovarian cancers, through direct and indirect mechanisms, including modulation of oestrogen metabolism. Cancer therapies might also alter microbiota at sites throughout the body. Reciprocally, microbiota composition can influence the efficacy and toxic effects of cancer therapies, as well as quality of life following cancer treatment. Modulation of the microbiome via probiotics or microbiota transplant might prove useful in improving responsiveness to cancer treatment and quality of life. Elucidating these complex host-microbiome interactions, including the crosstalk between distal and local sites, will translate into interventions for prevention, therapeutic efficacy and toxic effects to enhance health outcomes for women with gynaecological cancers.


Assuntos
Carcinogênese , Disbiose/microbiologia , Neoplasias dos Genitais Femininos/microbiologia , Genitália Feminina/microbiologia , Microbiota/fisiologia , Anti-Infecciosos/uso terapêutico , Bactérias Anaeróbias , Colo do Útero/microbiologia , Disbiose/metabolismo , Estrogênios/metabolismo , Tubas Uterinas/microbiologia , Feminino , Microbioma Gastrointestinal , Neoplasias dos Genitais Femininos/metabolismo , Neoplasias dos Genitais Femininos/prevenção & controle , Neoplasias dos Genitais Femininos/terapia , Genitália Feminina/metabolismo , Humanos , Lactobacillus , Ovário/microbiologia , Probióticos/uso terapêutico , Útero/microbiologia , Vagina/microbiologia
10.
Nat Commun ; 11(1): 199, 2020 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-31924800

RESUMO

Around 40% of preterm births are attributed to ascending intrauterine infection, and Ureaplasma parvum (UP) is commonly isolated in these cases. Here we present a mouse model of ascending UP infection that resembles human disease, using vaginal inoculation combined with mild cervical injury induced by a common spermicide (Nonoxynol-9, as a surrogate for any mechanism of cervical epithelial damage). We measure bacterial load in a non-invasive manner using a luciferase-expressing UP strain, and post-mortem by qPCR and bacterial titration. Cervical exposure to Nonoxynol-9, 24 h pre-inoculation, facilitates intrauterine UP infection, upregulates pro-inflammatory cytokines, and increases preterm birth rates from 13 to 28%. Our results highlight the crucial role of the cervical epithelium as a barrier against ascending infection. In addition, we expect the mouse model will facilitate further research on the potential links between UP infection and preterm birth.


Assuntos
Colo do Útero/lesões , Inflamação/metabolismo , Complicações Infecciosas na Gravidez , Ureaplasma/metabolismo , Animais , Proliferação de Células , Colo do Útero/microbiologia , Colo do Útero/patologia , Citocinas , Modelos Animais de Doenças , Feminino , Humanos , Recém-Nascido , Camundongos , Camundongos Endogâmicos C57BL , Nonoxinol , Gravidez
11.
PLoS One ; 15(1): e0224359, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31914129

RESUMO

Sexually transmitted infections (STIs) and vaginal dysbiosis (disturbed resident microbiota presenting with abnormal Nugent score or candidiasis) have been associated with mucosal inflammation and risk of HIV-1 infection, cancer and poor reproductive outcomes. To date, the temporal relationships between aberrant cervical innate immunity and the clinical onset of microbial disturbance have not been studied in a large population of reproductive age women. We examined data from a longitudinal cohort of 934 Ugandan and Zimbabwean women contributing 3,274 HIV-negative visits who had complete laboratory, clinical and demographic data. Among those, 207 women later acquired HIV, and 584 women were intermittently diagnosed with C. trachomatis (CT), N. gonorrhoeae (NG), genital herpes (HSV-2), T. vaginalis (TV), candidiasis, and abnormal intermediate (4-6) or high (7-10) Nugent score, i.e. bacterial vaginosis (BV). Immune biomarker concentrations in cervical swabs were analyzed by generalized linear and mixed effect models adjusting for site, age, hormonal contraceptive use (HC), pregnancy, breastfeeding, genital practices, unprotected sex and overlapping infections. High likelihood ratios (1.5-4.9) denoted the values of cervical immune biomarkers to predict onset of abnormal Nugent score and candidiasis at the next visits. When controlling for covariates, higher levels of ß-defensin-2 were antecedent to BV, CT and HSV-2, lower anti-inflammatory ratio IL-1RA:IL-1ß-to intermediate Nugent scores and candida, lower levels of the serine protease inhibitor SLPI-to candida, lower levels of the adhesion molecule ICAM-1 -to TV, and lower levels of the oxidative stress mitigator and endothelial activation marker VEGF-to NG. Changes in innate immunity following onset of dysbiosis and infections were dependent on HC use when controlling for all other covariates. In conclusion, imminent female genital tract dysbiosis or infection can be predicted by distinct patterns of innate immunity. Future research should characterize biotic and abiotic determinants of this pre-existing innate immunity state.


Assuntos
Disbiose/imunologia , Imunidade Inata/genética , Doenças Sexualmente Transmissíveis/imunologia , Vaginose Bacteriana/imunologia , Adolescente , Adulto , Biomarcadores/metabolismo , Colo do Útero/imunologia , Colo do Útero/microbiologia , Colo do Útero/patologia , Disbiose/epidemiologia , Disbiose/microbiologia , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/imunologia , Infecções por HIV/virologia , Humanos , Molécula 1 de Adesão Intercelular/imunologia , Molécula 1 de Adesão Intercelular/metabolismo , Proteína Antagonista do Receptor de Interleucina 1/imunologia , Proteína Antagonista do Receptor de Interleucina 1/metabolismo , Interleucina-1beta/imunologia , Interleucina-1beta/metabolismo , Estresse Oxidativo/imunologia , Gravidez , Infecções do Sistema Genital/epidemiologia , Infecções do Sistema Genital/imunologia , Inibidor Secretado de Peptidases Leucocitárias/imunologia , Inibidor Secretado de Peptidases Leucocitárias/metabolismo , Doenças Sexualmente Transmissíveis/epidemiologia , Doenças Sexualmente Transmissíveis/microbiologia , Uganda/epidemiologia , Vagina/imunologia , Vagina/microbiologia , Vaginose Bacteriana/epidemiologia , Vaginose Bacteriana/microbiologia , Fator A de Crescimento do Endotélio Vascular/imunologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Zimbábue/epidemiologia
12.
PLoS Pathog ; 16(1): e1008236, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31971984

RESUMO

Bacterial vaginosis (BV), a condition in which the vaginal microbiota consists of community of obligate and facultative anaerobes rather than dominated by a single species of Lactobacillus, affects ~30% of women in the US. Women with BV are at 60% increased risk for HIV acquisition and are 3-times more likely to transmit HIV to an uninfected partner. As cervicovaginal mucus (CVM) is the first line of defense against mucosal pathogens and the home of the resident vaginal microbiota, we hypothesized the barrier function of CVM to HIV may be diminished in BV. Here, we characterized CVM properties including pH, lactic acid content, and Nugent score to correlate with the microbiota community composition, which was confirmed by 16S rDNA sequencing on a subset of samples. We then quantified the mobility of fluorescently-labeled HIV virions and nanoparticles to characterize the structural and adhesive barrier properties of CVM. Our analyses included women with Nugent scores categorized as intermediate (4-6) and BV (7-10), women that were either symptomatic or asymptomatic, and a small group of women before and after antibiotic treatment for symptomatic BV. Overall, we found that HIV virions had significantly increased mobility in CVM from women with BV compared to CVM from women with Lactobacillus crispatus-dominant microbiota, regardless of whether symptoms were present. We confirmed using nanoparticles and scanning electron microscopy that the impaired barrier function was due to reduced adhesive barrier properties without an obvious degradation of the physical CVM pore structure. We further confirmed a similar increase in HIV mobility in CVM from women with Lactobacillus iners-dominant microbiota, the species most associated with transitions to BV and that persists after antibiotic treatment for BV. Our findings advance the understanding of the protective role of mucus and highlight the interplay between vaginal microbiota and the innate barrier function mucus.


Assuntos
Colo do Útero/microbiologia , Colo do Útero/virologia , Infecções por HIV/virologia , Vagina/microbiologia , Vagina/virologia , Vaginose Bacteriana/microbiologia , Adulto , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Coinfecção/microbiologia , Coinfecção/virologia , Feminino , HIV-1/fisiologia , Humanos , Microbiota , Pessoa de Meia-Idade , Muco/microbiologia , Muco/virologia , Adulto Jovem
13.
Am J Obstet Gynecol ; 222(5): 491.e1-491.e8, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31816307

RESUMO

BACKGROUND: The cervix functions as a barrier to ascending pathogens in pregnancy. Short cervical length and lack of cervicovaginal Lactobacillus species are risk factors for spontaneous preterm birth; however, whether they interact to increase risk remains unknown. OBJECTIVE: We sought to examine the relationship between cervicovaginal microbiota and short cervix as well as their combined impact on spontaneous preterm birth risk. STUDY DESIGN: This was a secondary analysis of a prospective nested, case-control pregnancy study. Cervical swabs were collected between 16 and 20 weeks of gestation. Cervical length was measured per standard clinical care during a clinically indicated ultrasound at approximately 20 weeks of gestation. Cervicovaginal microbiota were analyzed with 16S ribosomal RNA gene sequencing and classified into community state types among 67 cases of spontaneous preterm birth, 47 cases of medically indicated preterm birth, and 358 cases of term births. Logistic regression was used to model associations of community state type IV, a community characterized by a paucity of Lactobacillus species and a wide array of anaerobic bacteria, and short cervix (<25 mm) as well as to model the association of a combination of short cervix and community state type IV with the odds of spontaneous preterm birth. RESULTS: Among the 472 women in the data set, there were 38 with short cervix (8.1%) and 177 with community state type IV (37.5%). Short cervix was associated with spontaneous preterm birth (adjusted odds ratio, 15.59; 95% confidence interval, 6.77-35.92). Women with community state type IV had higher odds of short cervix (adjusted odds ratio, 2.17; 95% confidence interval, 1.04-4.53) as well as spontaneous preterm birth (adjusted odds ratio, 1.97; 95% confidence interval, 1.06-3.65). While the interaction of community state type IV and short cervix was not significant (P = .771), women with both short cervix and community state type IV (n = 20) had higher odds of spontaneous preterm birth compared with women with both normal cervical length and community state types I, II, III, or V (n = 277) (adjusted odds ratio, 21.8; 95% confidence interval, 6.78-70.2). CONCLUSION: Community state type IV, characterized by a diverse set of strict and facultative anaerobes and a paucity of Lactobacillus species, is associated with increased odds of short cervix. Women with both community state type IV and short cervix have higher odds of spontaneous preterm birth than women with either factor alone. Determining the cascade of events leading to premature cervical shortening, including dysbiosis, may be critical in preventing spontaneous preterm birth.


Assuntos
Colo do Útero/diagnóstico por imagem , Colo do Útero/microbiologia , Lactobacillus/isolamento & purificação , Segundo Trimestre da Gravidez , Vagina/microbiologia , Adulto , Estudos de Casos e Controles , Medida do Comprimento Cervical , Feminino , Humanos , Microbiota , Gravidez , Ultrassonografia Pré-Natal , Vagina/diagnóstico por imagem , Adulto Jovem
14.
PLoS Pathog ; 15(12): e1008136, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31790511

RESUMO

Sexually transmitted infections are a critical public health issue. However, the mechanisms underlying sexually transmitted infections in women and the link between the infection mechanism and the wide range of clinical outcomes remain elusive due to a lack of research models mimicking human infection in vivo. We established a human cervical tissue explant model to mimic local Neisseria gonorrhoeae (GC) infections. We found that GC preferentially colonize the ectocervix by activating integrin-ß1, which inhibits epithelial shedding. GC selectively penetrate into the squamocolumnar junction (TZ) and endocervical epithelia by inducing ß-catenin phosphorylation, which leads to E-cadherin junction disassembly. Epithelial cells in various cervical regions differentially express carcinoembryonic antigen-related cell adhesion molecules (CEACAMs), the host receptor for GC opacity-associated proteins (OpaCEA). Relatively high levels were detected on the luminal membrane of ecto/endocervical epithelial cells but very low levels intracellularly in TZ epithelial cells. CEACAM-OpaCEA interaction increased ecto/endocervical colonization and reduced endocervical penetration by increasing integrin-ß1 activation and inhibiting ß-catenin phosphorylation respectively, through CEACAM downstream signaling. Thus, the intrinsic properties of cervical epithelial cells and phase-variation of bacterial surface molecules both play a role in controlling GC infection mechanisms and infectivity, preferential colonization or penetration, potentially leading to asymptomatic or symptomatic infection.


Assuntos
Aderência Bacteriana/fisiologia , Colo do Útero/microbiologia , Gonorreia/microbiologia , Membrana Mucosa/microbiologia , Neisseria gonorrhoeae/patogenicidade , Colo do Útero/metabolismo , Feminino , Humanos , Membrana Mucosa/metabolismo , Técnicas de Cultura de Órgãos
16.
Asian Pac J Cancer Prev ; 20(12): 3843-3847, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31870131

RESUMO

OBJECTIVE: High-risk human papillomavirus (HR HPV) was associated with the development of cervical cancer. Asymptomatic Chlamydia trachomatis (C. trachomatis) infection is the most common bacterial, sexually-transmitted infection. This study aimed to investigate the association of C. trachomatis in positive HR HPV and the cytological results from liquid-based cytology (LBC). METHODS: 150 residual LBC specimens were collected; all of which had undergone cytology and HPV testing by Cobas. The samples were established as C. trachomatis using real-time PCR (RT-PCR) with Cryptic F/Cryptic R primers. RESULTS: Of 150 positive HPV findings, the most common (72.7%, 109/150) were the 12 other HR HPVs (viz., 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68). The cervical cytology of those positive HR HPVs were mostly negative (70.0%, 105/150).  The C. trachomatis infections in positive HR HPV were 16% (24/150) HPV. The analysis of the abnormal cytology revealed that 41.6% had C. trachomatis co-infection (C. trachomatis and HPV infection) viz., LSIL (20.8%), HSIL (12.5%), and ASC-US (8.3%). A comparison with positive HPV without C. trachomatis co-infection revealed that the highest prevalence was for LSIL, ASC-US, and HSIL (11.1%, 10.3%, and 6.4%, respectively). There was no difference between the abnormalities and negative cervical cytology with negative and positive C. trachomatis co-infection in HR HPV positive (p = 0.174). CONCLUSION: C. trachomatis infection was not significantly associated HR-HPV and abnormal cytology. This study confirms the increasing rate of C. trachomatis infection in asymptomatic women so routine screening for these infections has been suggested to (a) prevent complications such as the chronic pelvic pain associated with prolong infection and (b) reduce sexual transmission of the infection.


Assuntos
Colo do Útero/microbiologia , Colo do Útero/virologia , Infecções por Chlamydia/microbiologia , Coinfecção/complicações , Programas de Rastreamento/métodos , Infecções por Papillomavirus/virologia , Neoplasias do Colo do Útero/diagnóstico , Células Escamosas Atípicas do Colo do Útero/microbiologia , Células Escamosas Atípicas do Colo do Útero/virologia , Neoplasia Intraepitelial Cervical/diagnóstico , Neoplasia Intraepitelial Cervical/epidemiologia , Neoplasia Intraepitelial Cervical/microbiologia , Neoplasia Intraepitelial Cervical/virologia , Infecções por Chlamydia/complicações , Chlamydia trachomatis/isolamento & purificação , Coinfecção/microbiologia , Coinfecção/virologia , Feminino , Seguimentos , Humanos , Incidência , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/complicações , Prognóstico , Fatores de Risco , Lesões Intraepiteliais Escamosas/diagnóstico , Lesões Intraepiteliais Escamosas/epidemiologia , Lesões Intraepiteliais Escamosas/microbiologia , Lesões Intraepiteliais Escamosas/virologia , Tailândia/epidemiologia , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/microbiologia , Neoplasias do Colo do Útero/virologia , Esfregaço Vaginal/métodos
17.
Sci Rep ; 9(1): 19337, 2019 12 18.
Artigo em Inglês | MEDLINE | ID: mdl-31852945

RESUMO

Human papillomavirus (HPV) is a major pathogen that causes cervical cancer and many other related diseases. HPV infection related cervical microbiome could be an induce factor of cervical cancer. However, it is uncommon to find a single test on the market that can simultaneously provide information on both HPV and the microbiome. Herein, a novel method was developed in this study to simultaneously detect HPV infection and microbiota composition promptly and accurately. It provides a new and simple way to detect vaginal pathogen situation and also provide valuable information for clinical diagnose. This approach combined multiplex PCR, which targeted both HPV16 E6E7 and full-length 16S rRNA, and Nanopore sequencing to generate enough information to understand the vagina condition of patients. One HPV positive liquid-based cytology (LBC) sample was sequenced and analyzed. After comparing with Illumina sequencing, the results from Nanopore showed a similar microbiome composition. An instant sequencing evaluation showed that 15 min sequencing is enough to identify the top 10 most abundant bacteria. Moreover, two HPV integration sites were identified and verified by Sanger sequencing. This approach has many potential applications in pathogen detection and can potentially aid in providing a more rapid clinical diagnosis.


Assuntos
Colo do Útero/microbiologia , Colo do Útero/virologia , Citodiagnóstico/métodos , Microbiota , Sequenciamento por Nanoporos , Papillomaviridae/genética , Papillomaviridae/isolamento & purificação , Sequência de Bases , Bases de Dados Genéticas , Feminino , Humanos , Microbiota/genética , Anotação de Sequência Molecular , Infecções por Papillomavirus/virologia , RNA Ribossômico 16S/genética , Reprodutibilidade dos Testes , Integração Viral
18.
Integr Cancer Ther ; 18: 1534735419893063, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31833799

RESUMO

Human papillomavirus (HPV) infection is associated with the vast majority of cervical cancer cases as well as with other anogenital cancers. PepCan is an investigational HPV therapeutic vaccine for treating cervical high-grade squamous intraepithelial lesions. The present study was performed to test whether the cervical microbiome influences vaccine responses and to explore host factors as determinants of the cervical microbiome composition in women with biopsy-proven high-grade squamous intraepithelial lesions. In a recently completed Phase I clinical trial of PepCan, histological response rate of 45% (14 of 31 patients), a significant increase in circulating T-helper type 1 cells, and a significant decrease in HPV 16 viral load were reported. DNA, extracted from liquid cytology specimens collected before and after vaccinations, were amplified and then hybridized to a G4 PhyloChip assay to characterize the microbiome. We describe trends that certain bacterial taxa in the cervix may be enriched in non-responders in comparison to responders (Padj = .052 for phylum Caldithrix and Padj = .059 for phylum Nitrospirae). There was no difference in bacterial diversity between the 2 groups. A permutational analysis of variance performed for various demographic and immune parameters showed significant clustering with microbiome beta diversity for race, HPV 16 status, peripheral T-helper type 1 cells, and HLA-B40 (P = .001, .014, .037, and .024, respectively). Further analyses showed significant differences at the empirical Operational Taxonomic Unit level for race and HPV 16 status. As these results are from a small Phase I study, further studies are needed to examine the role of cervical microbiome in response to HPV therapeutic vaccines.


Assuntos
Colo do Útero/microbiologia , Microbiota/imunologia , Infecções por Papillomavirus/imunologia , Vacinas contra Papillomavirus/imunologia , Lesões Intraepiteliais Escamosas/imunologia , Neoplasias do Colo do Útero/imunologia , Adulto , Colo do Útero/imunologia , Feminino , Papillomavirus Humano 16/imunologia , Humanos , Pessoa de Meia-Idade , Infecções por Papillomavirus/microbiologia , Lesões Intraepiteliais Escamosas/microbiologia , Neoplasias do Colo do Útero/microbiologia , Carga Viral/imunologia , Adulto Jovem
19.
Enferm. infecc. microbiol. clín. (Ed. impr.) ; 37(10): 661-667, dic. 2019. tab
Artigo em Espanhol | IBECS | ID: ibc-189594

RESUMO

La cervicitis es un cuadro de inflamación del cuello uterino. Suele ser causada por un agente infeccioso, generalmente de transmisión sexual. Frecuentemente es asintomática, y la infección silente puede originar complicaciones del tracto genital superior. Los síntomas suelen ser inespecíficos, y los más significativos son aumento del flujo vaginal y/o sangrado intermenstrual. Para su diagnóstico existen sistemas comerciales basados en técnicas moleculares que incluyen la casi totalidad de los patógenos conocidos asociados a cervicitis, aunque los cultivos no deben abandonarse por la necesidad de realizar estudios de sensibilidad a los antibióticos. Se recomienda iniciar un tratamiento empírico que incluya C.trachomatis y N. gonorrhoeae en el caso de mujeres con elevado riesgo de infección por dichos patógenos, sobre todo si el seguimiento no está asegurado o no se dispone de pruebas diagnósticas adecuadas. En mujeres con bajo riesgo el tratamiento deberá ajustarse a los resultados de las pruebas microbiológicas


Cervicitis is the inflammation of the cervix. It is usually caused by an infectious agent, usually sexually transmitted. Cervicitis is frequently asymptomatic and silent infection can cause complications of the upper genital tract. The symptoms are usually nonspecific, the most significant being an increase in vaginal discharge and/or intermenstrual bleeding. For its diagnosis, there are commercial systems based on molecular techniques that include almost all of the known pathogens associated with cervicitis, although cultures should not be abandoned due to the need to conduct studies of susceptibility to antibiotics. It is recommended to initiate an empirical antibiotic therapy that covers C.trachomatis and N. gonorrhoeae in the case of women at high risk of infection by these pathogens, especially if the follow-up is not assured or adequate diagnostic tests are not available. In women with low risk of sexually transmitted infection, antibiotic therapy should be adjusted to the results of the microbiological results


Assuntos
Humanos , Feminino , Cervicite Uterina/etiologia , Cervicite Uterina/diagnóstico , Doenças Sexualmente Transmissíveis/epidemiologia , Cervicite Uterina/terapia , Técnicas Microbiológicas/métodos , Colo do Útero/anatomia & histologia , Colo do Útero/microbiologia , Mycoplasma genitalium/isolamento & purificação , Herpes Simples/microbiologia
20.
PLoS One ; 14(11): e0224658, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31738795

RESUMO

The cervical microbiota constitutes an important protective barrier against the invasion of pathogenic microorganisms. A disruption of microbiota within the cervical milieu has been suggested to be a driving factor of sexually transmitted infections. These include Chlamydia trachomatis which frequently causes serious reproductive sequelae such as infertility in women. In this study, we profiled the cervical microbial composition of a population of 70 reproductive-age Malaysian women; among which 40 (57.1%) were diagnosed with genital C. trachomatis infection, and 30 (42.8%) without C. trachomatis infection. Our findings showed a distinct compositional difference between the cervical microbiota of C. trachomatis-infected subjects and subjects without C. trachomatis infection. Specifically, significant elevations of mostly strict and facultative anaerobes such as Streptococcus, Megasphaera, Prevotella, and Veillonella in the cervical microbiota of C. trachomatis-positive women were detected. The results from the current study highlights an interaction of C. trachomatis with the environmental microbiome in the endocervical region.


Assuntos
Colo do Útero/microbiologia , Infecções por Chlamydia/microbiologia , Chlamydia trachomatis/isolamento & purificação , Infertilidade/microbiologia , Microbiota/imunologia , Centros Médicos Acadêmicos , Adulto , Bactérias Anaeróbias/imunologia , Bactérias Anaeróbias/isolamento & purificação , Infecções por Chlamydia/complicações , Infecções por Chlamydia/imunologia , Chlamydia trachomatis/patogenicidade , Estudos de Coortes , DNA Bacteriano/genética , DNA Bacteriano/isolamento & purificação , Feminino , Interações Hospedeiro-Patógeno/imunologia , Humanos , Infertilidade/imunologia , Malásia , Metagenômica , Microbiota/genética , Ambulatório Hospitalar , RNA Ribossômico 16S/genética , Adulto Jovem
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