Dataset Information

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

ABSTRACT: 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.

SUBMITTER: Dehon PM

PROVIDER: S-EPMC5470585 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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

Dehon Patricia M PM McGowin Chris L CL

Sexually transmitted diseases 20170701 7

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 inf ...[more]

PMID: 28608793

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Project description:Mycoplasmas contain glycoglycerolipids in their plasma membrane as key structural components involved in bilayer properties and stability. A membrane-associated glycosyltransferase (GT), GT MG517, has been identified in Mycoplasma genitalium, which sequentially produces monoglycosyl- and diglycosyldiacylglycerols. When recombinantly expressed in Escherichia coli, the enzyme was functional in vivo and yielded membrane glycolipids from which Glcβ1,6GlcβDAG was identified as the main product. A chaperone co-expression system and extraction with CHAPS detergent afforded soluble protein that was purified by affinity chromatography. GT MG517 transfers glucosyl and galactosyl residues from UDP-Glc and UDP-Gal to dioleoylglycerol (DOG) acceptor to form the corresponding β-glycosyl-DOG, which then acts as acceptor to give β-diglycosyl-DOG products. The enzyme (GT2 family) follows Michaelis-Menten kinetics. k(cat) is about 5-fold higher for UDP-Gal with either DOG or monoglucosyldioleoylglycerol acceptors, but it shows better binding for UDP-Glc than UDP-Gal, as reflected by the lower K(m), which results in similar k(cat)/K(m) values for both donors. Although sequentially adding glycosyl residues with β-1,6 connectivity, the first glycosyltransferase activity (to DOG) is about 1 order of magnitude higher than the second (to monoglucosyldioleoylglycerol). Because the ratio between the non-bilayer-forming monoglycosyldiacylglycerols and the bilayer-prone diglycosyldiacylglycerols contributes to regulate the properties of the plasma membrane, both synthase activities are probably regulated. Dioleoylphosphatidylglycerol (anionic phospholipid) activates the enzyme, k(cat) linearly increasing with dioleoylphosphatidylglycerol concentration. GT MG517 is shown to be encoded by an essential gene, and the addition of GT inhibitors results in cell growth inhibition. It is proposed that glycolipid synthases are potential targets for drug discovery against infections by mycoplasmas.

Project description:BackgroundMycoplasma genitalium (MG) causes urethritis, cervicitis and pelvic inflammatory disease. The MG treatment failure rate using 1 g azithromycin at an Australian Sexual Health clinic in 2007-9 was 31% (95%CI 23-40%). We developed a rapid high resolution melt analysis (HRMA) assay targeting resistance mutations in the MG 23S rRNA gene, and validated it against DNA sequencing by examining pre- and post-treatment archived samples from MG-infected patients.Methodology/principal findingsAvailable MG-positive pre-treatment (n = 82) and post-treatment samples from individuals with clinical treatment failure (n = 20) were screened for 23S rRNA gene mutations. Sixteen (20%) pre-treatment samples possessed resistance mutations (A2058G, A2059G, A2059C), which were significantly more common in patients with symptomatic azithromycin-treatment failure (12/26; 44%) than in those clinically cured (4/56; 7%), p<0.001. All 20 patients experiencing azithromycin-failure had detectable mutations in their post-treatment samples. In 9 of these cases, the same mutational types were present in both pre- and post-treatment samples indicating transmitted resistance, whilst in 11 of these cases (55%), mutations were absent in pre-treatment samples indicating likely selection of resistant isolates have occurred. HRMA was able to detect all mutational changes determined in this study by DNA sequencing. An additional HRMA assay incorporating an unlabelled probe was also developed to detect type 4 single-nucleotide polymorphisms found in other populations, with a slightly lower sensitivity of 90%.Conclusions/significanceTreatment failure is associated with the detection of macrolide resistance mutations, which appear to be almost equally due to selection of resistant isolates following exposure to 1 g azithromycin and pre-existing transmitted resistance. The application of a rapid molecular assay to detect resistance at the time of initial detection of infection allows clinicians to shorten the time to initiate effective second line treatment. This has the potential to reduce transmission of resistant strains and to avoid sequelae associated with persistent untreated infection.

Dataset Information

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

Publications

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

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