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Sorangicin A Is Active against Chlamydia in Cell Culture, Explanted Fallopian Tubes, and Topical In Vivo Treatment.

ABSTRACT: Current treatment of Chlamydia trachomatis using doxycycline and azithromycin introduces detrimental side effects on the host's microbiota. As a potential alternative treatment, the myxobacterial natural product sorangicin A (SorA) blocks the bacterial RNA polymerase. In this study we analyzed the effectiveness of SorA against C. trachomatis in cell culture, and explanted fallopian tubes and systemic and local treatment in mice, providing also pharmacokinetic data on SorA. Potential side effects of SorA on the vaginal and gut microbiome were assessed in mice and against human-derived Lactobacillus species. SorA showed minimal inhibitory concentrations of 80 ng/mL (normoxia) to 120 ng/mL (hypoxia) against C. trachomatis in vitro and was eradicating C. trachomatis at a concentration of 1 µg/mL from fallopian tubes. In vivo, SorA reduced chlamydial shedding by more than 100-fold within the first days of infection by topical application corresponding with vaginal detection of SorA only upon topical treatment, but not after systemic application. SorA changed gut microbial composition during intraperitoneal application only and did neither alter the vaginal microbiota in mice nor affect growth of human-derived lactobacilli. Additional dose escalations and/or pharmaceutical modifications will be needed to optimize application of SorA and to reach sufficient anti-chlamydial activity in vivo.

SUBMITTER: Graspeuntner S

PROVIDER: S-EPMC10215493 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature

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Sorangicin A Is Active against Chlamydia in Cell Culture, Explanted Fallopian Tubes, and Topical In Vivo Treatment.

Graspeuntner Simon S Koethke Katharina K Scholz Celeste C Semmler Lea L Lupatsii Mariia M Kirchhoff Laura L Herrmann Jennifer J Rox Katharina K Wittstein Kathrin K Käding Nadja N Hanker Lars C LC Stadler Marc M Brönstrup Mark M Müller Rolf R Shima Kensuke K Rupp Jan J

Antibiotics (Basel, Switzerland) 20230422 5

Current treatment of Chlamydia trachomatis using doxycycline and azithromycin introduces detrimental side effects on the host's microbiota. As a potential alternative treatment, the myxobacterial natural product sorangicin A (SorA) blocks the bacterial RNA polymerase. In this study we analyzed the effectiveness of SorA against C. trachomatis in cell culture, and explanted fallopian tubes and systemic and local treatment in mice, providing also pharmacokinetic data on SorA. Potentia ...[more]

PMID: 37237698

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Project description:ObjectiveTo determine if Chlamydia trachomatis (C. trachomatis) seropositivity, as detected by the C. trachomatis elementary body (EB)-based enzyme-linked immunosorbent assay [EB ELISA] predicts pregnancy and pregnancy outcome among infertile women with documented tubal patency.DesignCohort study.SettingOutpatient clinics.Patient(s)In all, 1,250 infertile women with documented tubal patency enrolled in 1 of 2 randomized controlled trials: Pregnancy in Polycystic Ovary Syndrome II; and the Assessment of Multiple Intrauterine Gestations From Ovarian Stimulation.Intervention(s)Sera were analyzed for anti-C. trachomatis immunoglobulin G (IgG)1 and IgG3 antibodies, using a research C. trachomatis EB ELISA. The optical density (OD)405 readings of ≥ 0.35 and ≥ 0.1 were considered positive for IgG1 and IgG3, respectively.Main outcome measure(s)Primary outcomes included pregnancy, live birth, and ectopic pregnancy. Log-linear regression was used to determine the relative risk after adjusting for age, race, treatment medication, smoking status, and current alcohol use.Result(s)A total of 243 (19%) women were seropositive for anti-C. trachomatis IgG3. They tended to be nonwhite and smokers. Anti-C. trachomatis IgG3 seropositive women were significantly less likely to conceive (risk ratio [RR] 0.65, 95% confidence interval [CI] 0.52-0.83) or to have a live birth (RR 0.59, 95% CI 0.43-0.80); these associations were weakened after adjusting for number of hysterosalpingography-documented patent tubes (RR 0.73, 95% CI 0.56-0.97) and (RR 0.73, 95% CI 0.50-1.04), respectively. Anti-C. trachomatis IgG3 seropositive women who conceived had a ×2.7 risk (95% CI 1.40-5.34) of ectopic pregnancy.Conclusion(s)Even in the presence of tubal patency, anti-C. trachomatis IgG3 seropositivity is associated with a lower likelihood of pregnancy. Anti-C. trachomatis IgG3 seropositive women have as high as 3 times the risk of ectopic pregnancy.Clinical trial registration numberPPCOSII: NCT00719186 and AMIGOS: NCT01044862.

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Sorangicin A Is Active against Chlamydia in Cell Culture, Explanted Fallopian Tubes, and Topical In Vivo Treatment.

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Sorangicin A Is Active against <i>Chlamydia</i> in Cell Culture, Explanted Fallopian Tubes, and Topical In Vivo Treatment.

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