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.

Intrauterine device use, sexually transmitted infections, and fertility: a prospective cohort study.

BACKGROUND: In the 1970s, numerous medical reports, media coverage, and litigation around the Dalkon Shield intrauterine device led to a perception that all intrauterine devices cause upper genital tract infection and infertility. OBJECTIVE: This study aimed to assess the association between intrauterine device use and time to conception. STUDY DESIGN: The Fertility After Contraceptive Termination Study is a multicenter, prospective cohort study of women stopping their contraceptive method to attempt conception. We recruited participants between 2011 and 2017. Participants were a convenience sample of women recruited from academic centers in Philadelphia, PA; Los Angeles, CA; St. Louis, MO; Indianapolis, IN; Aurora, CO; and Salt Lake City, UT. Women were eligible if they stopped their contraceptive method within the past 120 days before enrollment, were between 18 and 35 years of age, had no history of infertility or sterilization, and had at least 6 months of follow-up. Baseline data included demographic and reproductive characteristics, past contraceptive use, nucleic acid amplification testing for sexually transmitted infections, and serology for past infection with Chlamydia trachomatis, Trichomonas vaginalis, and Mycoplasma genitalium. The primary exposure was intrauterine device use (ever); the primary outcome was time to conception. All participants were observed longitudinally for up to 24 months. We used piecewise exponential proportional hazards models with multiple imputation to provide hazard ratios and their respective 95% confidence intervals. RESULTS: Of the 461 participants, mean age was 28.2 years, 178 (38.7%) were Black, 157 (34.1%) were considered as low socioeconomic status, and 275 (59.7%) had a history of intrauterine device use. Without adjusting for any covariates, the median time to conception was shorter for participants who had a history of intrauterine device use (5.1 months) than participants who never used an intrauterine device (7.5 months). After controlling for potential confounders, the association of past intrauterine device use with time to conception was not statistically significant (adjusted hazard ratio, 1.25; 95% confidence interval, 0.99-1.58). In our multivariable model, age, nulligravidity, Black race, low socioeconomic status, and past Mycoplasma genitalium infection were associated with longer times to conception (hazard ratio, 0.76; 95% confidence interval, 0.58-0.99). Conception by 12 months was lower in participants with past Mycoplasma genitalium infection (68% vs 80% without past infection; P=.019). CONCLUSION: We found no impairment of fertility with ever use of an intrauterine device. Serologic evidence of past Mycoplasma genitalium infection was associated with longer times to conception and higher rates of infertility. Mycoplasma genitalium infection is a potential modifiable cause of infertility.

Sequence variation and immunogenicity of the Mycoplasma genitalium MgpB and MgpC adherence proteins during persistent infection of men with non-gonococcal urethritis.

Mycoplasma genitalium is a sexually transmitted bacterial pathogen that infects men and women. Antigenic variation of MgpB and MgpC, the immunodominant adherence proteins of M. genitalium, is thought to contribute to immune evasion and chronic infection. We investigated the evolution of mgpB and mgpC sequences in men with non-gonococcal urethritis persistently infected with M. genitalium, including two men with anti-M. genitalium antibodies at enrollment and two that developed antibodies during follow-up. Each of the four patients was persistently infected with a different strain type and each patient produced antibodies targeting MgpB and MgpC. Amino acid sequence evolution in the variable regions of MgpB and MgpC occurred in all four patients with changes observed in single and multiple variable regions over time. Using the available crystal structure of MgpC of the G37 type strain we found that predicted conformational B cell epitopes localize predominantly to the variable region of MgpC, amino acids that changed during patient infection lie in these epitopes, and variant amino acids are in close proximity to the conserved sialic acid binding pocket. These findings support the hypothesis that sequence variation functions to avoid specific antibodies thereby contributing to persistence in the genital tract.

The two-sided role of the vaginal microbiome in Chlamydia trachomatis and Mycoplasma genitalium pathogenesis.

Sexually transmitted infections (STI) can have major consequences for the reproductive health of women. Mycoplasma genitalium is a STI that is not as well studied but causes pelvic inflammatory disease (PID) among other complications. Another well-known STI is Chlamydia trachomatis, notorious for its capability to cause infertility. Both C. trachomatis and M. genitalium share some of the same clinical aspects. Parts of the pathogenesis of C. trachomatis and M. genitalium infections are unclear but potential factors are the microbiome and other STIs. The healthy vaginal microbiome is dominated by Lactobacillus spp; these bacteria protect the host against invading bacteria like C. trachomatis and M. genitalium by producing antibacterial compounds and providing a mechanical barrier. A dysbiosis of the vaginal microbiome is characterized by a non-Lactobacillus spp. dominated microbiome, also known as bacterial vaginosis (BV). BV and BV associated bacteria play a role in the pathogenesis of STIs such as C. trachomatis and M. genitalium. The different species of BV associated bacteria have distinct characteristics that could play a role in C. trachomatis and M. genitalium infections. Host factors should also be considered when analysing the interaction of C. trachomatis and M. genitalium and the microbiome. One important factor is the hormonal homeostasis. Oral hormonal contraception influences the vaginal milieu and could influence the infection process of STIs. Overall, this review attempts to give an overview of the pathogenesisof C. trachomatis and M. genitalium infections and the relationship between M. genitalium, C. trachomatis, and the vaginal microbiome.

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.

Mycoplasma genitalium Nonadherent Phase Variants Arise by Multiple Mechanisms and Escape Antibody-Dependent Growth Inhibition.

Antigenic variation of the immunodominant MgpB and MgpC proteins has been suggested to be a mechanism of immune evasion of the human pathogen Mycoplasma genitalium, a cause of several reproductive tract disease syndromes. Phase variation resulting in the loss of adherence has also been documented, but the molecular mechanisms underlying this process and its role in pathogenesis are still poorly understood. In this study, we isolated and characterized 40 spontaneous, nonadherent phase variants from in vitro-passaged M. genitalium cultures. In all cases, nonadherence was associated with the loss of MgpBC protein expression, attributable to sequence changes in the mgpBC expression site. Phase variants were grouped into seven classes on the basis of the nature of the mutation. Consistent with the established role of RecA in phase variation, 31 (79.5%) variants arose via recombination with MgPa repeat regions that contain mgpBC variable sequences. The remaining mutants arose via nonsense or frameshift mutations. As expected, revertants were obtained for phase variants that were predicted to be reversible but not for those that arose via an irreversible mechanism. Furthermore, phase variants were enriched in M. genitalium cultures exposed to antibodies reacting to the extracellular, conserved C terminus of MgpB but not in cultures exposed to antibodies reacting to an intracellular domain of MgpB or the cytoplasmic HU protein. Genetic characterization of the antibody-selected phase variants confirmed that they arose via reversible and irreversible recombination and point mutations within mgpBC These phase variants resisted antibody-mediated growth inhibition, suggesting that phase variation promotes immune evasion.

The Unique Microbiology and Molecular Pathogenesis of Mycoplasma genitalium.

Mycoplasma genitalium is increasingly appreciated as a common cause of sexually transmitted disease syndromes, including urethritis in men and cervicitis, endometritis, pelvic inflammatory disease, and possibly preterm birth, tubal factor infertility, and ectopic pregnancy in women. Despite these disease associations, which parallel those of Chlamydia trachomatis and Neisseria gonorrhoeae, the mechanisms by which this pathogen elicits inflammation, causes cellular damage, and persists in its only natural host (humans) are unique and are not fully understood. The purpose of this review is to briefly provide a historical background on the discovery, microbiology, and recognition of M. genitalium as a pathogen, and then summarize the recent advances in our understanding of the molecular biology and pathogenesis of this unique urogenital organism. Collectively, the basic scientific discussions herein should provide a framework for understanding the clinical and epidemiological outcomes described in the accompanying articles in this supplemental issue.

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.

Macrolide and quinolone-resistant Mycoplasma genitalium in a man with persistent urethritis: the tip of the British iceberg?

There is growing concern worldwide for macrolide resistance in M. genitalium following liberal use of 1 g azithromycin to treat non-gonococcal urethritis and confirmed C. trachomatis infection. Moxifloxacin is the second-line treatment for M. genitalium and still has excellent efficacy against it. However, recent reports indicating that quinolone resistance is more prevalent than previously thought are worrying. Routine testing of symptomatic men and women for M. genitalium is not currently recommended in BASHH guidelines, and attempts to implement such testing have been hampered by a lack of commercially available assays. We present a case of M. genitalium urethritis which failed to respond to four different antibiotic regimens, resulting in multiple visits to the clinic and anxiety for the patient.

Experimental Infection of Pig-Tailed Macaques (Macaca nemestrina) with Mycoplasma genitalium.

Mycoplasma genitalium is an underappreciated cause of human reproductive tract disease, characterized by persistent, often asymptomatic, infection. Building on our previous experiments using a single female pig-tailed macaque as a model for M. genitalium infection (G. E. Wood, S. L. Iverson-Cabral, D. L. Patton, P. K. Cummings, Y. T. Cosgrove Sweeney, and P. A. Totten, Infect Immun 81:2938-2951, 2013, https://doi.org/10.1128/IAI.01322-12), we cervically inoculated eight additional animals, two of which were simultaneously inoculated in salpingeal tissue autotransplanted into abdominal pockets. Viable M. genitalium persisted in the lower genital tract for 8 weeks in three animals, 4 weeks in two, and 1 week in one; two primates resisted infection. In both animals inoculated in salpingeal pockets, viable M. genitalium was recovered for 2 weeks. Recovery of viable M. genitalium from lower genital tract specimens was improved by diluting the specimen in broth and by Vero cell coculture. Ascension to upper reproductive tract tissues was not detected, even among three persistently infected animals. M. genitalium-specific serum antibodies targeting the immunodominant MgpB and MgpC proteins appeared within 1 week in three animals inoculated both cervically and in salpingeal pockets and in one of three persistently infected animals inoculated only in the cervix. M. genitalium-specific IgG, but not IgA, was detected in cervical secretions of serum antibody-positive animals, predominantly against MgpB and MgpC, but was insufficient to clear M. genitalium lower tract infection. Our findings further support female pig-tailed macaques as a model of M. genitalium infection, persistence, and immune evasion.

Analysis of the Mycoplasma genitalium MgpB Adhesin to Predict Membrane Topology, Investigate Antibody Accessibility, Characterize Amino Acid Diversity, and Identify Functional and Immunogenic Epitopes.

Mycoplasma genitalium is a sexually transmitted pathogen and is associated with reproductive tract disease that can be chronic in nature despite the induction of a strong antibody response. Persistent infection exacerbates the likelihood of transmission, increases the risk of ascension to the upper tract, and suggests that M. genitalium may possess immune evasion mechanism(s). Antibodies from infected patients predominantly target the MgpB adhesin, which is encoded by a gene that recombines with homologous donor sequences, thereby generating sequence variation within and among strains. We have previously characterized mgpB heterogeneity over the course of persistent infection and have correlated the induction of variant-specific antibodies with the loss of that particular variant from the infected host. In the current study, we examined the membrane topology, antibody accessibility, distribution of amino acid diversity, and the location of functional and antigenic epitopes within the MgpB adhesin. Our results indicate that MgpB contains a single transmembrane domain, that the majority of the protein is surface exposed and antibody accessible, and that the attachment domain is located within the extracellular C-terminus. Not unexpectedly, amino acid diversity was concentrated within and around the three previously defined variable regions (B, EF, and G) of MgpB; while nonsynonymous mutations were twice as frequent as synonymous mutations in regions B and G, region EF had equal numbers of nonsynonymous and synonymous mutations. Interestingly, antibodies produced during persistent infection reacted predominantly with the conserved C-terminus and variable region B. In contrast, infection-induced antibodies reacted poorly with the N-terminus, variable regions EF and G, and intervening conserved regions despite the presence of predicted B cell epitopes. Overall, this study provides an important foundation to define how different segments of the MgpB adhesin contribute to functionality, variability, and immunogenicity during persistent M. genitalium infection.

Implementación de una reacción en cadena de la polimerasa cuantitativa para la detección de Mycoplasma genitalium / Implementation of a quantitative-polymerase chain reaction for the detection of Mycoplasma genitalium

El diagnóstico de las infecciones por Mycoplasma genitalium mediante métodos bacteriológicostradicionales resulta laborioso y poco práctico. Es por ello que los métodos moleculares basados en laamplificación del ADN se utilizan con fines diagnósticos de infecciones causadas por este microorganismo.En Cuba no existen informes de la implementación y utilización de los métodos de reacción en cadena dela polimerasa cuantitativa (qPCR) para la detección y cuantificación de este patógeno. En este trabajo seimplementó una qPCR para la detección y cuantificación de M genitalium mediante la amplificación de unfragmento del gen mgpB que codifica para la proteína adhesina celular, mediante la tecnología LightCycler® (Roche), utilizando los métodos de qPCR SYBR Green I y TaqMan. Se evaluó la especificidad y sensibilidad de dicha PCR utilizando ADN de M genitalium y de otros micoplasmas de origen humanos. Se logró la implementación de ambos métodos de qPCR con un límite de detección de 3,6 geq/μL, siendo la plataforma TaqMan la que mostró mejor eficiencia. Ambos métodos mostraron una alta especificidad para la detección de M genitalium y no se detectaron reacciones cruzadas con otros micoplasmas de origen humano. Se implementó por primera vez en Cuba una qPCR para la detección de M genitalium. El método TaqMan mostró mejor desempeño para la futura aplicación de esta metodología en muestras clínicas. El presente trabajo permitirá realizar estudios de caracterización genética y antigénica de las cepas circulantes en Cuba, útiles para conformar un inmunógeno vacunal(AU)

The diagnosis of M genitalium infections by bacteriological culture is not feasible due to slow growth and that is time-consuming. Consequently, molecular methods using DNA amplification are widely used in theinfection diagnosis procedure. There are no reports in Cuba of the implementation and use of quantitativePolymerase Chain Reaction methods for the detection and quantification of this pathogen. The aim of thisstudy was to implement a qPCR method for the detection of M genitalium by the amplification of the mgpBadhesin gene using two LightCycler® (Roche) protocols, SYBR Green I and TaqMan. The specifity andsensitivity were evaluated by using DNA of M. genitalium as well as other mycoplasms of human origin. Inboth qPCR-protocols, a limit of detection of 3.6 genome equivalents per μL template (geq/μL) was reached.The TaqMan protocol showed better efficiency than the SYBR Green assay. Both protocols showed a highspecificity for the detection of M. genitalium, without cross-reactions with other mycoplasmas of humanorigin. For the first time in Cuba, a qPCR for detection of M. genitalium was implemented. The TaqManmethod showed a better performance than the SYBR method and should be used for future applications inclinical samples. The present work will allow performing future studies of genetic and antigenic characterization of the circulating strains in Cuba, useful as vaccine immunogen(AU)

Binding of CD14 to Mycoplasma genitalium-derived lipid-associated membrane proteins upregulates TNF-α.

Lipid-associated membrane proteins (LAMPs) are a mixture of mycoplasmal lipoproteins expressed on the surface, and they are the main structures for interaction with the host cells. The objective of this study was to explore the role of CD14 in immune recognition of Mycoplasma genitalium-derived LAMPs and investigate whether the binding of CD14 to LAMPs affects the inflammatory response. Enzyme-linked immunosorbent assay (ELISA), transient co-transfection, dual-luciferase reporter assay, specific inhibition assay, and competitive inhibition ELISA (CI-ELISA) were used. CD14 was involved in LAMP-stimulated production of tumor necrosis factor (TNF)-α by blocking CD14 antibody in THP-1 cells. Co-transfection experiments in HeLa cells provide evidence that CD14 facilitates LAMP-induced TNF-α release via toll-like receptor 2 (TLR2). In addition, LAMP-induced TNF-α release was increased by soluble CD14 but decreased by soluble TLR2. Lipid moieties of LAMPs pre-treated with lipoprotein lipase were responsible for TNF-α production. The binding of CD14 to LAMPs was supported by binding assay and CI-ELISA. Thus, we provide evidences that CD14 is not only able to recognize LAMPs but also its binding to LAMPs upregulates TNF-α release. These findings provide insight into the function of CD14 and the pathogenesis of mycoplasmal infections.

Persistence, immune response, and antigenic variation of Mycoplasma genitalium in an experimentally infected pig-tailed macaque (Macaca nemestrina).

Mycoplasma genitalium is a sexually transmitted pathogen associated with several acute and chronic reproductive tract disease syndromes in men and women. To evaluate the suitability of a pig-tailed macaque model of M. genitalium infection, we inoculated a pilot animal with M. genitalium strain G37 in the uterine cervix and in salpingeal pockets generated by transplanting autologous Fallopian tube tissue subcutaneously. Viable organisms were recovered throughout the 8-week experiment in cervicovaginal specimens and up to 2 weeks postinfection in salpingeal pockets. Humoral and cervicovaginal antibodies reacting to MgpB were induced postinoculation and persisted throughout the infection. The immunodominance of the MgpB adhesin and the accumulation of mgpB sequence diversity previously observed in persistent human infections prompted us to evaluate sequence variation in this animal model. We found that after 8 weeks of infection, sequences within mgpB variable region B were replaced by novel sequences generated by reciprocal recombination with an archived variant sequence located elsewhere on the chromosome. In contrast, mgpB region B of the same inoculum propagated for 8 weeks in vitro remained unchanged. Notably, serum IgG reacted strongly with a recombinant protein spanning MgpB region B of the inoculum, while reactivity to a recombinant protein representing the week 8 variant was reduced, suggesting that antibodies were involved in the clearance of bacteria expressing the original infecting sequence. Together these results suggest that the pig-tailed macaque is a suitable model to study M. genitalium pathogenesis, antibody-mediated selection of antigenic variants in vivo, and immune escape.

A comprehensive proteome of Mycoplasma genitalium.

Mycoplasma genitalium is a human pathogen associated with several sexually transmitted diseases. Proteomic technologies, along with other methods for global gene expression analysis, play a key role in understanding the mechanisms of bacterial pathogenesis and physiology. The proteome of M. genitalium, model of a minimal cell, has been extended using a combination of different proteomic approaches and technologies. The total proteome of this microorganism has been analyzed using gel-based and gel-free approaches, achieving the identification of 85.3% of the predicted ORFs. In addition, a comprehensive analysis of membrane subproteome has been performed. For this purpose, the TX-114 soluble fraction has been analyzed as well as the surface proteins, using cell-surface protein labeling with CyDye. Finally, the serological response of M. genitalium-infected patients and healthy donors has been analyzed to identify proteins that trigger immunological response. Here, we present the most extensive M. genitalium proteome analysis (85.3% of predicted ORFs), a comprehensive M. genitalium membrane analysis, and a study of the human serological response to M. genitalium.

Difficulties experienced in defining the microbial cause of pelvic inflammatory disease.

Clinical assessment of women with pelvic pain was a poor indicator of disease seen at laparoscopy. Thus, of 109 women, 22 at laparoscopy had salpingitis, 19 had adhesions without salpingitis, 20 had endometriosis or ovarian pathology and 48 no observable abnormality. In all laparoscopic categories, Ureaplasma spp. and Mycoplasma hominis, but not Mycoplasma genitalium, were at least as common in the cervix/vagina as Chlamydia trachomatis and equally frequent in the endometrium. However, C. trachomatis had the greatest propensity for spread to the Fallopian tubes. Thus, of 28 women who had C. trachomatis organisms in the vagina/cervix, 13 had them in a Fallopian tube (ratio 2.2:1); the ratio was 6:1 for Neisseria gonorrhoeae, 8:1 for M. genitalium, 21:1 for M. hominis and 31:1 for Ureaplasma spp. M. hominis organisms in a large number were detected most often in women with salpingitis. The likelihood of spread of Ureaplasma urealyticum and U. parvum from the lower to the upper genital tract was about the same and they were detected only once each in a tube, which was not inflamed in either case. Multiple bacteria were often detected at a single site, making it difficult to establish the exact cause of disease. However N. gonorrhoeae was considered to be the sole cause of salpingitis in one woman and the primary or equal primary contributor in four others; C. trachomatis was involved in at least 11 women, mostly as the sole cause or as the primary contributor; M. genitalium was considered the cause in one woman and had possible involvement in three others; and M. hominis was a questionable sole cause in one woman and the primary or equal primary contributor in three. Serologically, C. trachomatis was related to adhesions, without salpingitis, more often (63%) than any other micro-organism. M. genitalium may have been implicated in one case. Serologically, a previous C. trachomatis infection was indicated in 40% of women without an observable laparoscopic abnormality. C. trachomatis in the endometrium and tubes of women without any laparoscopic abnormality suggests subclinical disease, endometritis or endosalpingitis. There was evidence for a smaller proportion (19%) of women without an abnormality having been infected previously with M. genitalium. To some extent this is consistent with the infrequency of acute M. genitalium infections in this cohort of women.

Detection of Mycoplasma genitalium-reactive cervicovaginal antibodies among infected women.

Mycoplasma genitalium-reactive cervicovaginal IgA and IgG antibodies were detected in 51.9% and 70.4% of 27 infected women and 22.2% and 18.5% of 27 uninfected controls, respectively. The predominance of MgpB- and MgpC-reactive antibodies at the site of infection is consistent with their hypothesized role in selecting antigenic variants during persistent infection.

Chlamydia trachomatis and Mycoplasma genitalium plasma antibodies in relation to epithelial ovarian tumors.

OBJECTIVE: To assess associations of Chlamydia trachomatis and Mycoplasma genitalium antibodies with epithelial ovarian tumors. METHODS: Plasma samples from 291 women, undergoing surgery due to suspected ovarian pathology, were analyzed with respect to C. trachomatis IgG and IgA, chlamydial Heat Shock Protein 60-1 (cHSP60-1) IgG and M. genitalium IgG antibodies. Women with borderline tumors (n=12), ovarian carcinoma (n=45), or other pelvic malignancies (n=11) were matched to four healthy controls each. RESULTS: Overall, there were no associations of antibodies with EOC. However, chlamydial HSP60-1 IgG antibodies were associated with type II ovarian cancer (P=.002) in women with plasma samples obtained >1 year prior to diagnosis (n=7). M. genitalium IgG antibodies were associated with borderline ovarian tumors (P=.01). CONCLUSION: Chlamydial HSP60-1 IgG and M. genitalium IgG antibodies are in this study associated with epithelial ovarian tumors in some subsets, which support the hypothesis linking upper-genital tract infections and ovarian tumor development.