Impact of First-Line Antimicrobials on Chlamydia trachomatis-Induced Changes in Host Metabolism and Cytokine Production

Käding, Nadja; Schmidt, Nis; Scholz, Celeste; Graspeuntner, Simon; Rupp, Jan; Shima, Kensuke

doi:10.3389/fmicb.2021.676747

Cited by 3 publications

(3 citation statements)

References 60 publications

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“…Reflecting more the physiological situation of female infections, SorA was additionally tested in an ex vivo human fallopian tube model. This model is frequently used to transfer findings from cell culture or mice to a more complex model of genital tract chlamydial infections in humans [17,[34][35][36]. In accordance with the in vitro findings, SorA at concentrations of 1 to 2 µg/mL significantly reduced chlamydial growth and progeny in human fallopian tubes, pointing at the need to closely monitor the required dose to be reached in the infected tissue.…”

Section: Discussionmentioning

confidence: 73%

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

et al. 2023

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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.

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Section: Discussionmentioning

confidence: 73%

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

et al. 2023

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“…Overall, these data could be interpreted to indicate that post-treatment, due to a direct impact of azithromycin or the impact of the therapy on the local tissue and microbial environment, conditions may be altered, resulting in repeat chlamydial infections having distinctive gene expression profiles. In support of these scenarios microbiome shifts have been reported after azithromycin therapy ( 70 ), and distinct impacts of azithromycin on metabolism and cytokine responses have also been recently reported ( 71 ). Alternatively, it is possible that new infections are highly transcriptionally active, regardless of whether they are repeat exposures or not, as we do not know the timeframes of the infections from the index samples.…”

Section: Discussionmentioning

confidence: 85%

Repeat infections with chlamydia in women may be more transcriptionally active with lower responses from some immune genes

Huston

Lawrence

Wee

et al. 2022

Front. Public Health

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Chlamydia trachomatis, the most common bacterial sexually transmitted infection worldwide, is responsible for considerable health burden due to its significant sequelae. There are growing concerns about chlamydial treatment and management due to widely documented increasing burden of repeat infections. In the current study, a cohort study design of 305 women with urogenital chlamydial infections demonstrated that 11.8% of women experienced repeat infections after treatment with azithromycin. The chlamydial DNA load measured by quantitative PCR was higher in women who experienced a repeat infection (p = 0.0097) and repeat infection was associated with sexual contact. There was no genomic or phenotypic evidence of azithromycin resistance within the chlamydial isolates. During repeat infection, or repeat positive tests during follow up, vaginal chlamydial gene expression (ompA, euo, omcB, htrA, trpAB) was markedly higher compared to baseline, and two of the selected immune genes analyzed had significantly lower expression at the time of repeat infection. Overall, there are two implications of these results. The results could be generalized to all recent infections, or repeat positive events, and indicate that chlamydial infections are have higher transcriptional activity of select genes early in the infection in women. Alternatively, after azithromycin treatment, repeat infections of Chlamydia may be more transcriptionally active at certain genes, and there may be post-treatment immunological alterations that interplay into repeat exposures establishing an active infection. The potential that recent infections may involve a higher level of activity from the organism may have implications for management by more regular testing of the most at risk women to reduce the risk of sequelae.

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“…Chlamydia trachomatis is an important pathogen in non-gonococcal cervicitis (Marrazzo and Martin, 2007). Käding et al showed that first-line antimicrobials, such as doxycycline (100mg twice daily for 7 days) and azithromycin (1g in a single dose), have been recommended for the treatment of Chlamydia trachomatis infection, with reported efficacy rates of 100% and 97% respectively (Käding et al, 2021). The commonly used therapeutic agents for Mycoplasma genitalium include macrolides (e.g., azithromycin, pristinamycin), tetracyclines (e.g., doxycycline, minocycline), and quinolones (e.g., moxifloxacin, sitafloxacin) (Jensen et al, 2021(Jensen et al, 2022.…”

Section: Antibioticsmentioning

confidence: 99%

Deciphering the role of female reproductive tract microbiome in reproductive health: a review

Gao,

Liu,

Wang

et al. 2024

Front. Cell. Infect. Microbiol.

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Relevant studies increasingly indicate that female reproductive health is confronted with substantial challenges. Emerging research has revealed that the microbiome interacts with the anatomy, histology, and immunity of the female reproductive tract, which are the cornerstone of maintaining female reproductive health and preventing adverse pregnancy outcomes. Currently, the precise mechanisms underlying their interaction and impact on physiological functions of the reproductive tract remain elusive, constituting a prominent area of investigation within the field of female reproductive tract microecology. From this new perspective, we explore the mechanisms of interactions between the microbiome and the anatomy, histology, and immunity of the female reproductive tract, factors that affect the composition of the microbiome in the female reproductive tract, as well as personalized medicine approaches in managing female reproductive tract health based on the microbiome. This study highlights the pivotal role of the female reproductive tract microbiome in maintaining reproductive health and influencing the occurrence of reproductive tract diseases. These findings support the exploration of innovative approaches for the prevention, monitoring and treatment of female reproductive tract diseases based on the microbiome.

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Impact of First-Line Antimicrobials on Chlamydia trachomatis-Induced Changes in Host Metabolism and Cytokine Production

Cited by 3 publications

References 60 publications

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

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

Repeat infections with chlamydia in women may be more transcriptionally active with lower responses from some immune genes

Deciphering the role of female reproductive tract microbiome in reproductive health: a review

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