Mycoplasma genitalium Provokes Seminal Inflammation among Infertile Males.

The impact of sexually transmitted infections (STI) on male fertility is controversial. Aims: To investigate the prevalence of urethritis-associated STIs (chlamydia, gonorrhoeae, Mycoplasma genitalium, trichomoniasis) among infertile males; to analyze the effect of STIs on semen parameters and blood PSA. Case-control study. Study group (n = 2000): males with fertility problems or desire for fertility check. Control group (n = 248): male partners of pregnant women. Analyses: polymerase chain reaction for STI, seminal interleukin 6 (IL-6), semen and fractionated urine, blood analyses (PSA, reproductive hormones). The prevalence of M. genitalium and chlamydia in the study group was 1.1% and 1.2%, respectively. The prevalence of chlamydia in the control group was 1.6%, while there were no M. genitalium cases. No cases with gonorrhoeae or trichomoniasis or combined infections were observed in neither group. There was a higher seminal concentration of neutrophils and IL-6 among M. genitalium positives compared with STI negatives. There was a trend toward a lower total count of spermatozoa and progressive motility among STI positives. No impact of STIs on PSA was found. The prevalence of STIs among infertile males is low. M. genitalium is associated with seminal inflammation. The impact of STIs on semen parameters deserves further investigations.

Mycoplasma genitalium and M. pneumoniae Regulate a Distinct Set of Protein-Coding Genes in Epithelial Cells.

Mycoplasma genitalium and M. pneumoniae are two significant mycoplasmas that infect the urogenital and respiratory tracts of humans. Despite distinct tissue tropisms, they both have similar pathogenic mechanisms and infect/invade epithelial cells in the respective regions and persist within these cells. However, the pathogenic mechanisms of these species in terms of bacterium-host interactions are poorly understood. To gain insights on this, we infected HeLa cells independently with M. genitalium and M. pneumoniae and assessed gene expression by whole transcriptome sequencing (RNA-seq) approach. The results revealed that HeLa cells respond to M. genitalium and M. pneumoniae differently by regulating various protein-coding genes. Though there is a significant overlap between the genes regulated by these species, many of the differentially expressed genes were specific to each species. KEGG pathway and signaling network analyses revealed that the genes specific to M. genitalium are more related to cellular processes. In contrast, the genes specific to M. pneumoniae infection are correlated with immune response and inflammation, possibly suggesting that M. pneumoniae has some inherent ability to modulate host immune pathways.

Serologic markers of Chlamydia trachomatis and other sexually transmitted infections and subsequent ovarian cancer risk: Results from the EPIC cohort.

A substantial proportion of epithelial ovarian cancer (EOC) arises in the fallopian tube and other epithelia of the upper genital tract; these epithelia may incur damage and neoplastic transformation after sexually transmitted infections (STI) and pelvic inflammatory disease. We investigated the hypothesis that past STI infection, particularly Chlamydia trachomatis, is associated with higher EOC risk in a nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort including 791 cases and 1669 matched controls. Serum antibodies against C. trachomatis, Mycoplasma genitalium, herpes simplex virus type 2 (HSV-2) and human papillomavirus (HPV) 16, 18 and 45 were assessed using multiplex fluorescent bead-based serology. Conditional logistic regression was used to estimate relative risks (RR) and 95% confidence intervals (CI) comparing women with positive vs. negative serology. A total of 40% of the study population was seropositive to at least one STI. Positive serology to C. trachomatis Pgp3 antibodies was not associated with EOC risk overall, but with higher risk of the mucinous histotype (RR = 2.30 [95% CI = 1.22-4.32]). Positive serology for chlamydia heat shock protein 60 (cHSP60-1) was associated with higher risk of EOC overall (1.36 [1.13-1.64]) and with the serous subtype (1.44 [1.12-1.85]). None of the other evaluated STIs were associated with EOC risk overall; however, HSV-2 was associated with higher risk of endometrioid EOC (2.35 [1.24-4.43]). The findings of our study suggest a potential role of C. trachomatis in the carcinogenesis of serous and mucinous EOC, while HSV-2 might promote the development of endometrioid disease.

High rates of treatment failure for Mycoplasma genitalium among men and women attending a sexual health clinic.

BACKGROUND: Mycoplasma genitalium (Mgen) causes non-gonococcal urethritis (NGU) and is believed to cause pelvic inflammatory disease (PID). High rates of macrolide resistance are well documented globally for Mgen. In Brighton, patients with NGU and PID are tested for Mgen and test of cure (TOC) offered post-treatment. METHODS: Demographic, clinical and treatment history data were collected over a 12-month period for all Mgen-positive patients in a Brighton-based genitourinary clinic. RESULTS: There were 114 patients with Mgen. 18% (61/339) of men with NGU and 9% (15/160) of women with PID had Mgen. 62/114 (54%) returned for first test TOC 4 weeks after treatment. 27/62 (44%) had a positive TOC; 25/27 (92.6%) had received azithromycin first line (500 mg stat then 250 mg OD for 4 days), 1/27 (3.7%) had received moxifloxacin first line (400 mg OD for 14 days) and 1/27 (3.7%) had received doxycycline first line (100 mg BD for 7 days). 20/27 (74%) returned for a second TOC 4 weeks later. 5/20 (25%) patients were positive on second TOC; 3/5 (60%) had received azithromycin second line and 2/5 (40%) had received moxifloxacin second line. Patients were more likely to have a positive TOC if they were at risk of reinfection (9/27 positive TOC vs 3/35 negative TOC; p=0.02). Patients given moxifloxacin were more likely to have a negative TOC (1/27 positive TOC vs 9/35 negative TOC; p=0.03) than those who received other antibiotic regimens. CONCLUSIONS: Treatment failure rates for Mgen following azithromycin use are substantial, raising concerns regarding resistance. However, reinfection risk may contribute, suggesting a requirement for improved public awareness and clinician knowledge.

Sexually transmitted infections and risk of epithelial ovarian cancer: results from the Nurses' Health Studies.

BACKGROUND: Sexually transmitted infections (STIs) are associated with pelvic inflammatory disease and tubal pathologies. Given the tubal origin of a proportion of ovarian cancers, STIs may be relevant in their aetiology. METHODS: Antibodies indicating past infection with Chlamydia trachomatis, Mycoplasma genitalium, herpes simplex virus type 2, and against human papillomavirus oncogenes (L1 and E6+E7 oncoproteins of types 16, 18, 45) were measured in prediagnosis plasma samples in a nested case-control study in the Nurses' Health Studies (n = 337 cases 1:1 matched to controls). Logistic regression was used to estimate multivariable-adjusted relative risks (RRs) and 95% confidence intervals [CIs] comparing women seropositive vs. seronegative among all cases (invasive and borderline), invasive (n = 257), and invasive serous ovarian cancers; n = 170), and borderline ovarian tumours (n = 80). RESULTS: C. trachomatis seropositivity was associated with higher risk of ovarian cancer overall (RR = 2.07 [1.25-3.43]); results were similar for invasive, invasive serous, and borderline tumours. We observed no associations for the other STIs. Relative to women seronegative to all infections, strongest associations were observed for seropositivity to C. trachomatis plus another STI (2.74 [1.20-6.27]; C. trachomatis alone, 1.88 [1.03-3.42]; all cases); however, the RRs were not significantly different. CONCLUSIONS: C. trachomatis infection may increase ovarian cancer risk; additional studies are required.

Mycoplasma genitalium can modulate the local immune response in patients with endometriosis.

OBJECTIVE: To detect Mollicutes in women with endometriosis and healthy peritoneal tissues and evaluate the participation of these bacteria in the immune response during endometriosis. DESIGN: Cross-sectional study. SETTING: University hospitals. PATIENT (S): Women with endometriosis (n = 73) and without endometriosis (n = 31). INTERVENTION(S): Endocervical swabs, peritoneal fluid, and biopsied lesions of endometriosis of women with endometriosis (study group) and healthy peritoneal tissues (control group) were collected during surgery. Clinical characteristics were registered before surgery. MAIN OUTCOME MEASURE(S): We determined the infectious agents with the use of quantitative polymerase chain reaction (PCR). The cytokine secretion profile was determined with the use of Luminex. The expression of immune response related genes was determined with the use of a PCR array kit. RESULT(S): All target microorganisms were detected at least once in the swab samples analyzed. It was possible to observe higher diversity of microorganisms in the samples of swab and peritoneal fluid in the study group compared with the control. Ureaplasma parvum was associated with the severity of the symptom dyspareunia. Mycoplasma genitalium was associated with higher production of interferon-γ and interleukin-1ß. Genes of inflammatory response activation and antigen presentation were up-regulated in biopsied tissue of women with endometriosis. In women with endometriosis, peritoneal fluid cells showed a down-regulation of genes associated with the inflammatory response. This down-regulation profile was higher in presence of M. genitalium. CONCLUSION(S): Mycoplasma genitalium may play a key role in the immune tolerance process and, especially, the aggravation of this profile. More studies are needed to understand this immune tolerance profile of bacterial infections.

The Immunopathogenesis of Mycoplasma genitalium Infections in Women: A Narrative Review.

Mycoplasma genitalium is a common, predominately asymptomatic, and often undiagnosed sexually transmitted infection that is associated with inflammatory urogenital and reproductive tract disease syndromes of men and women. Without programmatic screening in the United States, and with increasing resistance to antibiotics used in empiric sexually transmitted infection management, undiagnosed M. genitalium infections put many women at risk for cervicitis and pelvic inflammatory disease. Chronic infection may also lead to tubal-factor infertility, adverse pregnancy outcomes in expectant mothers, and is a risk factor for acquisition and transmission of human immunodeficiency virus. This review details the dynamics of M. genitalium infection, and then examines the potentially deleterious role of host immunity in reproductive tract disease pathogenesis and enhanced human immunodeficiency virus acquisition/transmission.

Sexually transmitted diseases treatment guidelines, 2015.

These guidelines for the treatment of persons who have or are at risk for sexually transmitted diseases (STDs) were updated by CDC after consultation with a group of professionals knowledgeable in the field of STDs who met in Atlanta on April 30-May 2, 2013. The information in this report updates the Sexually Transmitted Diseases Treatment Guidelines, 2010 (MMWR Recomm Rep 2010;59 [No. RR-12]). These updated guidelines discuss 1) alternative treatment regimens for Neisseria gonorrhoeae; 2) the use of nucleic acid amplification tests for the diagnosis of trichomoniasis; 3) alternative treatment options for genital warts; 4) the role of Mycoplasma genitalium in urethritis/cervicitis and treatment-related implications; 5) updated HPV vaccine recommendations and counseling messages; 6) the management of persons who are transgender; 7) annual testing for hepatitis C in persons with HIV infection; 8) updated recommendations for diagnostic evaluation of urethritis; and 9) retesting to detect repeat infection. Physicians and other health-care providers can use these guidelines to assist in the prevention and treatment of STDs.

Mycoplasma genitalium and cancer: a brief review.

Approximately, 15-20% of all cancers worldwide are caused by infectious agents. Understanding the role of infectious agents on cancer development might be useful for developing new approaches to its prevention. Mycoplasma genitalium is a clinically important sexually transmitted pathogen that has been associated with several human diseases. There have been a few studies suggestive of probable roles of Mycoplasma genitalium in cancer development, including prostate and ovarian cancers and lymphomas, but the role of this microorganism like other Mycoplasma species in neoplasia is still conjectural. Considering the prevalence of Mycoplasma genitalium infections and also the emergence of resistant strains, Mycoplasma genitalium needs more attention in the infectious agent cancer-causing research area.

A serine/threonine phosphatase encoded by MG_207 of Mycoplasma genitalium is critical for its virulence.

BACKGROUND: Bacterial signal transduction systems like two component system (TCS) and Serine/Threonine kinase (STK) and Serine/Threonine phosphatase (STP) play important roles in the virulence and pathogenesis of bacterial pathogens. Mycoplasma genitalium, a mollicute that causes the urogenital diseases urethritis and cervicitis in men and women, respectively, is a pathogen which lacks TCS but possesses STK/STP. In this study, we investigated the biochemical and virulence properties of an STP protein encoded by the gene MG_207 of this species. RESULTS: We overexpressed MG207 in Escherichia coli overexpression system as a recombinant His10MG207 protein and purified it with affinity chromatography. This recombinant protein readily hydrolyzed the substrate p-nitrophenyl phosphate (pNPP) in a dose-dependent manner. Additional studies using synthetic peptides as substrates revealed that the recombinant protein was able to hydrolyze the threonine phosphate. Further, a transposon insertion mutant strain of M. genitalium (TIM207) that lacks the protein MG207 showed differentially phosphorylated proteins when compared to the wild type G37 strain. Mass spectrometry revealed that some of the key proteins differentially phosphorylated in TIM207 strain were putative cytoskeletal protein encoded by the gene MG_328 and pyruvate dehydrogenase E1 α chain encoded by the gene MG_274. In addition, TIM207 was noticed to be less cytotoxic to HeLa cells and this correlated with the production of less hydrogen peroxide by this strain. This strain was also less efficient in inducing the differentiation of THP-1 cell line as compared to wild type M. genitalium. CONCLUSIONS: The results of the study suggest that MG207 is an important signaling protein of M. genitalium and its presence may be crucial for the virulence of this species.

Urethritis/cervicitis pathogen prevalence and associated risk factors among asymptomatic HIV-infected patients in South Africa.

BACKGROUND: To determine sexually transmitted infection (STI) prevalence, and patient characteristics associated with detection of urethritis/cervicitis pathogens, among HIV-infected individuals offered voluntary STI screening at a South African HIV treatment center. METHODS: Individuals, asymptomatic for genital discharge, were screened for Neisseria gonorrhoeae (NG), Chlamydia trachomatis, Trichomonas vaginalis (TV), Mycoplasma genitalium (MG) infections (real-time polymerase chain reaction assay), for syphilis and herpes simplex type 2 (serologically), and for bacterial vaginosis and Candida (microscopy, women only). Patients' most recent CD4 and viral load results were recorded. Demographic, clinical, and behavioral data were collected by nurse-administered questionnaire. RESULTS: Compared with men (n = 551), women (n = 558) were younger (mean age, 35.0 vs. 37.9 years; P < 0.001), reported more STIs in the past year (65.5% vs. 56.5%; P = 0.002), had more urethritis/cervicitis pathogens detected (21.3% vs.16.4%, P = 0.035), and were less aware of their partner's HIV status (53.1% vs. 62.3%; P = 0.007). The overall prevalence of individual urethritis/cervicitis pathogens was TV (7.6%), MG (6.1%), NG (5.4%), and C. trachomatis (2.1%). Multivariate analysis highlighted 4 significant factors associated with the detection of specific urethritis/cervicitis pathogens, namely female gender (TV, adjusted odds ratio [aOR] 2.53, 95% confidence interval [CI]: 1.47-4.37), having a regular sexual partner in the past 3 months (NG, aOR 2.26, 95% CI: 1.01-5.08), suboptimal condom use with regular partners (TV, aOR 2.07, 95% CI: 1.25-3.42), and a history of genital warts in the past year (NG, 2.25, 95% CI: 1.26-4.03). CONCLUSIONS: Asymptomatic urethritis/cervicitis pathogens were highly prevalent in this population. Few urethritis/cervicitis pathogen-associated patient characteristics were identified, emphasizing the need for affordable STI diagnostics to screen HIV-infected patients.

Methionine sulfoxide reductase A (MsrA) deficient Mycoplasma genitalium shows decreased interactions with host cells.

Mycoplasma genitalium is an important sexually transmitted pathogen that affects both men and women. In genital-mucosal tissues, it initiates colonization of epithelial cells by attaching itself to host cells via several identified bacterial ligands and host cell surface receptors. We have previously shown that a mutant form of M. genitalium lacking methionine sulfoxide reductase A (MsrA), an antioxidant enzyme which converts oxidized methionine (Met(O)) into methionine (Met), shows decreased viability in infected animals. To gain more insights into the mechanisms by which MsrA controls M. genitalium virulence, we compared the wild-type M. genitalium strain (G37) with an msrA mutant (MS5) strain for their ability to interact with target cervical epithelial cell lines (HeLa and C33A) and THP-1 monocytic cells. Infection of epithelial cell lines with both strains revealed that MS5 was less cytotoxic to HeLa and C33A cell lines than the G37 strain. Also, the MS5 strain was more susceptible to phagocytosis by THP-1 cells than wild type strain (G37). Further, MS5 was less able to induce aggregation and differentiation in THP-1 cells than the wild type strain, as determined by carboxyfluorescein diacetate succinimidyl ester (CFSE) labeling of the cells, followed by counting of cells attached to the culture dish using image analysis. Finally, MS5 was observed to induce less proinflammatory cytokine TNF-α by THP-1 cells than wild type G37 strain. These results indicate that MsrA affects the virulence properties of M. genitalium by modulating its interaction with host cells.