Search Results (548)

Host genetic susceptibility to urogenital Chlamydia trachomatis (Ct) reinfection remains poorly understood. Coding variants identified in prior genome-wide association studies (GWAS) explained only a small fraction of the risk of reinfection. Our goal in this study was to characterize whether more risk would be captured by sequence variation that traditional GWAS insufficiently captures. Specifically, we evaluated the risk attributable to SNPs present in regulatory, non-coding regions; post-transcriptional regulation by microRNAs (miRNAs) that may depend on sequence variation in either the miRNA or the target mRNA; and copy number variants (CNVs). We analyzed GWAS data from African American women with or without documented urogenital Ct reinfection. Fine mapping and independent association analyses identified 30 unique index single-nucleotide polymorphisms (iSNPs), which were expanded to variants in linkage disequilibrium. Regulatory annotation was performed using HaploReg, RegulomeDB, FORGEdb, rSNPBase, and GTEx. We examined whether genes identified in the Ct reinfection GWAS are targeted by known Ct infection–associated microRNAs using curated databases. Genome-wide CNV calling was conducted using SNP intensity data, followed by stringent quality control and gene-level association testing. Functional annotation prioritized 7 SNPs with strong regulatory evidence, with stringent criteria for regulatory relevance, using HaploReg, RegulomeDB, FORGEdb, and rSNPBase. The strongest signals were observed at the CHIT1 locus, where multiple intronic variants (including rs2486963 and rs2244385) overlapped regulatory chromatin, altered transcription factor binding motifs, and acted as cis-expression quantitative trait loci for CHIT1 in whole blood. Additional regulatory variants were identified near TDRP, ERICH1, and DLGAP1, showing tissue-specific regulatory effects. MicroRNA analysis revealed extensive post-transcriptional targeting of SOCS6 and SULF1, while CHIT1 showed no curated Ct-associated miRNA interactions. CNV analysis identified 5775 high-confidence events, with nominal gene-level associations observed for ATAD3A, CARD14, TMEM240, and ZNF140. These results indicate that a greater fraction of the susceptibility to urogenital Ct reinfection may be driven by genetic variation affecting immune and epithelial pathways rather than protein-coding changes. Full article

The treatment of intracellular bacterial infections such as Chlamydia remains a significant clinical challenge due to rising antibiotic resistance and persistent, immunopathology-driven tissue damage. Macrophages are essential for host defense; they can originate from both tissue-resident precursors and circulating monocytes. During infection, macrophages at infected sites are largely derived from monocytes that migrate and differentiate there, where they phagocytose pathogens and orchestrate immune responses. The chemokine receptor CCR2 is a key regulator of this process, yet its role beyond monocyte trafficking is not fully understood. Previous studies have shown that CCR2 deficiency impairs monocyte mobilization and exacerbates disease during Chlamydia infection, shifting immune responses away from protective Th1 immunity toward pathological Th2 and Th17 polarization. Here, we investigate how CCR2 regulates macrophage function to balance protective Th1 versus pathological Th2/Th17 immunity during Chlamydia respiratory infection. Our results show that CCR2 deficiency reduces pulmonary infiltration of Ly6C^hi and Ly6C^low monocytes and shifts macrophage differentiation away from an M1-like toward an M2-like phenotype. Mechanistically, CCR2 deficiency compromises macrophage endocytosis and survival, elevates ROS production, and activates the NLRP3 inflammasome, leading to Caspase-3/GSDME-mediated pyroptosis with increased IL-1β and IL-18, while suppressing the Caspase-1/GSDMD pathway. These findings were recapitulated in vitro using C. muridarum-stimulated Ccr2-deficient bone marrow-derived macrophages (BMDMs), which also showed impaired migration, reduced M1-like polarization, diminished endocytosis, and enhanced ROS/NLRP3/pyroptosis. Furthermore, co-culture of these BMDMs with CD4⁺ T cells revealed that Th1 differentiation was inhibited, whereas Th2 and Th17 responses were promoted. Collectively, CCR2 orchestrates monocyte–macrophage function by driving M1-like polarization and inhibiting NLRP3/Caspase-3/GSDME pyroptosis to rebalance Th1/Th2/Th17 immunity, thereby enhancing bacterial clearance while mitigating immunopathological tissue damage during Chlamydia infection. Full article

Background/Objectives: Chlamydia trachomatis (CT) is a prevalent sexually transmitted pathogen associated with pelvic inflammatory disease, infertility, and has been proposed as a potential contributor to carcinogenesis through chronic inflammation and tissue remodeling. The molecular mechanisms triggered by CT infection in fallopian tube cellular contexts and their relevance to ovarian cancer transcriptomes remain incompletely understood. Methods: We analyzed GSE109428, profiling primary human fallopian tube mesenchymal cells infected with CT, to identify differentially expressed genes and characterize affected pathways using g:Profiler and STRING protein–protein association networks (confidence ≥ 0.7). To provide translational context, we computed ssGSEA scores in TCGA-OV for four signatures capturing IFN/ISG, TNF/NF-κB, NOD/innate immunity, and ECM programs, and evaluated inter-signature correlations and exploratory associations with overall survival (OS) and progression-free interval (PFI). Results: CT infection induced sustained inflammatory and interferon-associated transcriptional programs, with STRING networks highlighting cytokine hubs and a densely connected ISG module. Genes downregulated at 48 h post-infection (48-hpi) showed coherent enrichment for ECM organization and adhesion pathways. In TCGA-OV (n = 307), inflammatory and innate immune signatures co-occurred across tumors, with moderate correlations between TNF/NF-κB and NOD/innate (ρ = 0.591) and IFN/ISG and NOD/innate (ρ = 0.534). Exploratory survival analyses showed no significant associations with OS or PFI in Kaplan–Meier analyses or multivariable Cox models, including clinically adjusted and tumor microenvironment-adjusted specifications. Conclusions: CT infection induces sustained inflammatory and interferon-linked programs and coordinated repression of ECM networks in fallopian tube mesenchymal cells. Analogous immune transcriptional states co-occur in ovarian tumors, though the signatures evaluated did not yield robust prognostic signals in TCGA-OV. As this is an entirely in silico study without experimental validation, these findings should be treated as hypothesis-generating; thus, further mechanistic and experimental studies are warranted to clarify how CT infection-associated pathways may intersect with female tumorigenesis. Full article

Background: Acanthamoeba is a free-living protozoan widely distributed in the environment and causes Acanthamoeba keratitis, skin, and brain disease. Acanthamoeba can exchange genes, potentially increasing antimicrobial resistance and virulence. Therefore, this systematic review aimed to summarize published studies on horizontal gene transfer (HGT) between Acanthamoeba and its intracellular microorganisms and to evaluate the impact of HGTs on the pathogenicity of Acanthamoeba. Methods: This systematic review was conducted following the recommended reporting guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) statement guideline. The electronic databases PubMed, Embase, and Web of Science were used to search for relevant published research articles. Results: Nineteen studies that fulfilled the inclusion criteria were included in this systematic review. A total of 14 (73.6%) studies reported evidence of HGT involving Acanthamoeba, and five studies of the nineteen (26.3%) analysed the presence of intracellular microorganisms on the pathological effects of the host Acanthamoeba. Horizontally transferred genes were predominantly reported from Pseudomonas species, Legionella pneumophila, and Chlamydia species. Conclusions: HGT can occur among intracellular microorganisms and their host Acanthamoeba. Acanthamoeba harbouring intracellular microbes showed enhanced pathogenic effects on human corneal epithelial cells and in a mouse model. However, heterogeneity among the included studies precluded meta-analysis. Studies using clinical and environmental samples are needed to characterize the horizontal transfer of virulence and antimicrobial resistance genes. Full article

Background and Objectives: Classical cardiovascular risk factors account for only a fraction of acute coronary syndromes (ACSs), and chronic Chlamydia pneumoniae infection has been proposed as a contributor to atherogenesis through persistent inflammation and endothelial dysfunction. We tested whether C. pneumoniae infection is independently associated with ACS by quantifying seroprevalence, inflammatory markers, and their relationship with conventional cardiovascular risk factors. Materials and Methods: In a prospective case–control design, we enrolled 47 patients with ACSs (29 with acute myocardial infarction and 18 with unstable angina) and 53 age- and locality-matched controls at Alexandria University Hospital. The clinical evaluation comprised electrocardiography, echocardiography, lipid profile, and high-sensitivity C-reactive protein (CRP). C. pneumoniae-specific IgG and IgM were measured by ELISA, with positive samples confirmed by microimmunofluorescence. Logistic regression models were adjusted for age, sex, hypertension, diabetes, dyslipidemia, and smoking. Results: IgM was undetectable in all 100 participants, excluding acute infection. IgG seropositivity was higher in cases than in controls (83.0% vs. 60.4%; OR: 3.20; 95% CI: 1.23–8.30; p = 0.017) and remained suggestive after multivariable adjustment (adjusted OR: 4.59; 95% CI: 1.33–18.28; p = 0.021), although the estimate is imprecise and does not meet our prespecified multivariate threshold of p < 0.01. Within the ACS cohort, IgG seropositivity was not significantly associated with CRP elevation (Fisher’s exact p = 1.000). CRP elevation was near-universal in cases (93.6%) and absent in controls (0%; p < 0.001). Conclusions: Chronic C. pneumoniae infection was associated with ACS in unadjusted analysis, with a suggestive but underpowered signal after multivariable adjustment, although the observational design precludes causal inference, and reverse causality cannot be excluded. Prospective studies using direct pathogen detection are required to determine whether the association reflects a contributory mechanism or shared susceptibility. Full article

Sexually transmitted infections (STIs) caused by C. trachomatis and HPV are the most prevalent worldwide. College students are characterized by being young women of reproductive age who may have risky sexual behavior. To describe the prevalence and factors associated with endocervical infection by C. trachomatis and HPV in college women in the Brazilian Amazon. Endocervical secretions were collected. The ompA gene of C. trachomatis and the L1 gene of HPV were detected. The Chi-square test, Fisher’s exact test, G test, Odds Ratio, and Multiple Logistic Regression were used with 95% confidence interval and p ≤ 0.05. The overall prevalence of endocervical infection by C. trachomatis was 8.3% (25/302) and by HPV was 28.9% (87/302). Low income was associated with sexually transmitted infection by C. trachomatis (14.8%, p = 0.0336). Those under 25 years old had twice the chance of HPV infection [39.3%, (OR: 2.6989), 95% CI: 1.6054–4.5371, p = 0.0002], as did women without children [31.8%, (OR: 2.333), CI: 1.1235–4.8461, p = 0.0307]. Women who did not study in a public school had 63% reduced risk of acquiring HPV infection [45.8% (OR: 0.3713), CI: 0.1951–0.7064, p = 0.0035]. C. trachomatis and HPV infections were present in low-income, childless young women who attended public schools, requiring the intensification of STI prevention policies in the Amazon region. Full article

Bacterial sexually transmitted and sexually associated infections remain a major global health concern, increasingly complicated by antimicrobial resistance and the limited effectiveness of existing therapies. In this context, bacteriophage-based and phage-derived approaches have re-emerged as potential alternative antibacterial strategies. This narrative review examines their applicability across key bacterial pathogens associated with sexually transmitted infections, including Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma genitalium, Treponema pallidum and biofilm-associated bacterial vaginosis, with a particular focus on pathogen-specific biological barriers. Available evidence indicates that the success of phage-based interventions is strongly dependent on factors such as intracellular localisation, structural characteristics of the bacterial envelope and the presence of polymicrobial biofilms. While phage-derived platforms, including endolysins, depolymerases and engineered phages, demonstrate antibacterial activity in experimental settings, their effectiveness is uneven across different pathogens. Biofilm-associated infections appear more accessible to these approaches, whereas intracellular and structurally atypical bacteria are currently considered more challenging targets based on available mechanistic and experimental evidence. These observations highlight the need for pathogen-specific engineering strategies and delivery systems. Overall, phage-based therapeutics in this field should be considered within a framework that integrates biological constraints with targeted antimicrobial design. Full article

Sexually transmitted diseases (STDs) continue to represent a substantial burden on public health and society worldwide. With significant implications for social, economic, and public health, STDsare a major global health concern. Despite advances in treatment, the global control of STDs is increasingly threatened by high prevalence of asymptomatic infections, delayed diagnosis and the rapid emergence of antimicrobial resistance (AMR). This emergence includes the value of asymptomatic screeningand the ensuing collateral damage resulting from the overuse of our declining potent antimicrobial resources. This review article critically examines current trends in the epidemiology, clinical significance, and laboratory diagnosis of major sexually transmitted pathogens, including Treponema pallidum, Chlamydia trachomatis, Trichomonas vaginalis, human papillomavirus, herpes simplex virus, and emerging sexually transmissible infections. Major emphasis is focused on contemporary diagnostic technologies and strategies, with a major focus on nucleic acid-based and point-of-care testing and their applicability in routine testing. The review also highlights evolving AMR patterns, resistance-guided therapy, and the role of global and national surveillance systems in informing treatment guidelines, with the integration of diagnostic strategies with resistance-guided therapy and surveillance systems. Strengthening diagnostic capacity, antimicrobial stewardship, and integrated surveillance is essential to mitigate resistance, improve patient outcomes, and advance effective STD management in venereology practice. Full article

Brucellosis, a zoonotic disease caused by Brucella, requires rapid, accurate, and sensitive diagnostic methods for effective prevention and control. This study presents the development of a fluorescence microsphere immunochromatographic assay (QDMs-ICA) for detecting anti-Brucella antibodies in bovine serum and milk. Lipopolysaccharide (LPS) from the Brucella abortus strain A19 was immobilized on the nitrocellulose membrane (NC membrane) as the test line (T-line), while rabbit anti-SPG polyclonal antibody was applied as the control line (C-line). Recombinant streptococcal protein G conjugated with quantum dot microspheres (QDMs-SPG) served as the detection conjugate. After optimizing the preparation parameters of QDMs-ICA, the method demonstrated sensitivities of approximately 0.98 IU/mL for bovine serum and 1.56 IU/mL for milk. No cross-reactions were observed with antibody-positive sera from Coxiella burnetii, Mycobacterium avium paratuberculosis, Mycobacterium tuberculosis, Chlamydia abortus, Bacillus anthracis, Escherichia coli O157:H7, Vibrio cholerae or Salmonella, indicating excellent specificity. In intra- and inter-batch repeatability tests, the coefficient of variation (CV) remained below 15%, confirming good reproducibility. The detection limit remained stable after storage at 37 °C for 7 days. Parallel testing of 150 bovine serum samples and 80 milk samples showed a high degree of concordance with the ID-VET commercial kit, with coincidence rates of 97.3% and 96.3%, respectively. These results demonstrate that QDMs-ICA offers high specificity, sensitivity, repeatability, and reliability, making it an effective tool for the rapid detection and epidemiological monitoring of brucellosis. Full article

Background and Objectives: The microbiome plays a pivotal role in male infertility, with distinct microbial species exerting both beneficial and deleterious effects on reproductive function. Sexually transmitted bacteria and several viruses, including human papillomavirus (HPV), have been identified in semen. This cross-sectional study aimed to examine the prevalence of single and co-infections of sexually transmitted bacteria (STB)—such as Chlamydia trachomatis, Mycoplasma spp., and Ureaplasma spp.—with various HPV subtypes in Greek male partners of infertile couples and to evaluate their potential impact on sperm parameters. In addition, the possible effect of cryopreservation on the maintenance of these pathogens was assessed. Materials and Methods: Eighty-two semen samples were initially collected from 82 individuals undergoing routine sperm analysis. In total, 80/82 (97.6%) participants proceeded to further analysis, as 2/82 (2.4%) were excluded due to poor DNA quality. Results: A total of 18/80 (22.5%) sperm samples tested positive for STB, with Ureaplasma spp. representing the most frequently detected pathogen. Co-infection of Ureaplasma spp. and Mycoplasma hominis was observed in 4/80 (5%) samples. Twelve samples (12/80, 15%) were positive for HPV, including low-risk (LR) and high-risk (HR) types, and HPV 16 was the predominant HR genotype. Notably, a co-infection of STB and HPV was not found in our specimens. STB-positive samples demonstrated significantly higher sperm concentration and improved progressive motility compared with STB-negative samples. HPV-positive samples exhibited lower sperm volume and concentration and increased non-progressive motility compared with HPV-negative samples. Following three months of cryopreservation, LR HPV and STB were no longer detectable, whereas HR HPV types remained detectable. Conclusions: These preliminary findings are interesting, as they could be useful for routine screening of HPV and STB in sperm samples preserved in sperm banks and highlight the need for future research. Full article

Ovarian cancer (OC) remains the most lethal gynecologic malignancy worldwide, largely due to late-stage diagnosis and the absence of effective screening strategies. As a result, primary prevention is a critical approach to reducing disease burden. This narrative review summarizes current evidence on modifiable lifestyle, reproductive, and environmental factors associated with OC risk, based on a comprehensive PubMed, MEDLINE, Scopus, and Web of Science search conducted through April 2026. Consistent protective associations have been reported for reproductive factors, including parity, breastfeeding, oral contraceptive use, salpingectomy, and tubal ligation. Among lifestyle factors, excess body weight is modestly associated with increased OC risk, while evidence regarding physical activity remains inconclusive. Diets rich in fiber and aligned with a Mediterranean pattern appear protective, potentially through hormonal modulation and anti-inflammatory effects. In contrast, pro-inflammatory diets high in trans fats and refined carbohydrates may increase risk, whereas omega-3 fatty acids show potential protective benefits. Chronic pelvic inflammation, particularly related to Chlamydia trachomatis infection, has been linked to elevated epithelial OC risk. Smoking demonstrates a dose–response association with mucinous tumors. Environmental exposures, including genital talc use and endocrine-disrupting chemicals such as phthalates and bisphenols, have linked to a possible, albeit modest, increase in risk, although the causal mechanisms remain uncertain. Although individual associations are generally modest, their cumulative population impact may be substantial. Integrating lifestyle-based prevention strategies into gynecologic practice and public health initiatives could represent a cost-effective approach to reducing OC incidence and improving women’s health outcomes. Full article

Chlamydia trachomatis has evolved sophisticated mechanisms to manipulate key host cell signaling pathways to facilitate its intracellular reproduction. N6-methyladenosine (m6A) in RNA is known to regulate various physiological and disease processes, and is also involved in the regulation of pathogenic and developmental processes in many pathogens. However, the specific impact of m6A modification on the intracellular growth of C. trachomatis remains poorly understood. In this study, our analysis of the m6A methylation profiles of host cell mRNAs following C. trachomatis infection revealed significant alterations in the distribution of m6A modifications, methylation motifs, and m6A-modified host target genes. We further demonstrate that chlamydial intracellular reproduction is mediated by the host methyltransferase-like (METTL) enzyme METTL14. Silencing METTL14 significantly reduced the reproduction efficiency of C. trachomatis. Mechanistically, C. trachomatis activates the Mitogen-Activated Protein Kinase (MAPK) and Phosphatidylinositol 3-kinase/Protein Kinase B (PI3K/AKT) signaling pathways through METTL14, thereby inhibiting host cell apoptosis and promoting intracellular bacterial reproduction. Collectively, these findings identify METTL14 as a key host factor for chlamydial intracellular reproduction, providing new mechanistic insights and potential targets for therapeutic intervention. Full article

Background: Molecular diagnostics may detect several respiratory pathogens simultaneously with rapid turnaround times. The aim of this study was to determine the frequency and distribution of respiratory pathogens among symptomatic outpatients. Methods: All outpatients presented for testing due to suspected acute respiratory infection between 1 January and 31 December 2024 to the Teaching Institute for Public Health of Split-Dalmatia County, Croatia, and multiplex real-time PCRs for 13 respiratory pathogens were included. Results: Out of 15,437 analyzed panels, 8878 (57.5%) were positive. Single-pathogen infections dominated (82.6%), while co-infections were recorded in 17.4% of panels; therefore, a total of 10,546 individual pathogens were detected, which were mostly viruses (87.0%). The following distribution of pathogens was observed: rhinovirus/enterovirus in 38.9% of positive results, influenza A virus in 14.5%, SARS-CoV-2 in 9.5%, parainfluenza virus in 7.9%, respiratory syncytial virus in 7.3%, Mycoplasma pneumoniae in 4.9%, Bordetella pertussis in 4.6%, human metapneumovirus in 4.2%, adenovirus in 3.4%, Chlamydia pneumoniae in 3.4%, influenza B virus in 1.3%, Bordetella parapertussis in 0.1% and Legionella pneumophila had one positive result. The first trimester of the year had the highest number of positive test panels (47.0%). Conclusions: Our study demonstrates a predominance of viral pathogens across all age groups and seasons, further supporting guideline-based practice and highlighting the importance of confirming bacterial infection before initiating antibiotic therapy. This insight into the post-pandemic circulation of respiratory pathogens may help inform public health strategies, including improved surveillance, anticipation of seasonal outbreaks, and targeted interventions, thereby supporting future pandemic preparedness and mitigation efforts. Full article

Background/Objectives: Mycoplasma genitalium is an emerging cause of sexually transmitted infections (STIs) and is increasingly recognized for its association with cervicitis and pelvic inflammatory disease. However, prevalence data in specific Japanese subpopulations, particularly comparing pregnant and non-pregnant women, remains limited. This study aimed to determine the prevalence of M. genitalium and its co-infection rates with Chlamydia trachomatis and Neisseria gonorrhoeae among Japanese women. Methods: A cross-sectional study was conducted using vaginal swab specimens collected between April 2021 and November 2022 from patients visiting two clinics in Gifu, Japan. The study population comprised 2138 non-pregnant women presenting with urogenital symptoms or sexual contact history, and 236 pregnant women undergoing routine antenatal screening. Detection was performed using real-time polymerase chain reaction assays on the cobas^® 8800 system (Roche Diagnostics). Results: Among non-pregnant women, the overall prevalence was 3.8% (82/2138) for M. genitalium, 3.4% (72/2138) for C. trachomatis, and 0.4% (9/2138) for N. gonorrhoeae. Co-infection rates were low; M. genitalium and C. trachomatis co-infection was observed in 0.2% of cases. Among pregnant women, the prevalence was 3.8% (9/236) for both M. genitalium and C. trachomatis, and 0.4% (1/236) for N. gonorrhoeae. No statistically significant differences in prevalence were observed between pregnant and non-pregnant women for any pathogen. Conclusions: The prevalence of M. genitalium in this Japanese cohort was comparable to that of C. trachomatis in both pregnant and non-pregnant women, highlighting its significance as a major STI pathogen. These findings underscore the importance of including M. genitalium in routine STI screening panels for symptomatic women and antenatal care to prevent reproductive health complications. Given the high rates of antimicrobial resistance documented in Japanese M. genitalium strains, specific diagnostic testing is essential to enable targeted, resistance-guided therapy. Full article

SARS-CoV-2 is a zoonotic virus with a proven ability to infect various animal species, including domestic cats. In the post-pandemic period of COVID 19, limited data still exist on the clinical course, shedding of infectious virus and diagnostic features in cats. The aim of this study was to investigate the spread of SARS-CoV-2 in cats in 2023, the clinical manifestations of the infection, the diagnostic algorithm, including molecular detection of viral components, the differential diagnosis of co-infection with FHV, FCV, Mycoplasma spp. and Chlamydia felis, serology, and the isolation of infectious SARS-CoV-2. The immunomodulatory therapy in animals with a standalone SARS-CoV-2 infection was applied. The study included oropharyngeal, conjunctival and nasal swab samples from 102 domestic cats with clinical signs. Of them, 20.6% (21/102) were positive for SARS-CoV-2, with 16.67% (17/102) of the cats showing various variants of co-infection with FHV, FCV, Mycoplasma spp. and Chlamydia felis. Four of the cats had a standalone SARS-CoV-2 with mild clinical manifestations that included serous discharges from the eyes, without change in the general condition. The virus was isolated from these samples. These four cats and their owners were positive for antibodies to the virus, and the owners were PCR-negative. The treatment of SARS-CoV-2 infection included the preparations Viusid, RX immunosuport, Vetomun and Lisymun. This is one of the first post-pandemic studies covering FHV, FCV, Mycoplasma spp. and Chlamydia felis in domestic cats with SARS-CoV-2 infection and further expands on the essential main idea including the specified pathogens of interest. Full article