Impact of metabolic changes triggered by microenvironmental factors on the efficacy of antimicrobials against Chlamydia trachomatis

Project: DFG ProjectsDFG Individual Projects

Project Details

Description

Urogenital tract infections with Chlamydia trachomatis are the most prevalent bacterial sexually transmitted diseases worldwide. C. trachomatis recurrent or persistent infections can lead to serious sequelae such as pelvic inflammatory disease (PID), ectopic pregnancy and infertility. Doxycycline and azithromycin are first-line drugs in treating C. trachomatis infection. However, treatment failures occur in around 8% of the patients. The reason is not yet completely understood and we wonder what kind of bacterial and host factors associate with treatment failures. A transient form of decreased susceptibility of antibiotics in the absence of a genetic change has been described for extracellular bacteria. In this form of phenotypic resistance changes in the bacterial metabolism seem to influence the antimicrobial efficacy. Phenotypic resistance in chlamydial infection was reported in vitro in the chlamydial persistent state or under low oxygen conditions (2% O2). It was shown that C. trachomatis in these growth states is less susceptible to antibiotics. However, the mechanism of this are still poorly investigated. As an obligate-intracellular bacteria C. trachomatis have a reduced genome size harboring incomplete metabolic pathways. Therefore C. trachomatis depend on host metabolites. Certain stimuli inducing chlamydial persistence such as Interferon-gamma are associated with changes in the energy metabolism of the host cell. In addition, low oxygen conditions (hypoxia, 2% O2) influence the host cell metabolism in which they stimulated the glycolysis and production of lactate. Moreover, an increased proton production accounts for a drop in the pH value. While it has been reported that an altered pH directly affected the antibiotic efficacy against extracellular bacterial uropathogens, it is so far not known how the metabolic activity or an alteration in the pH impacts the antibiotic efficacy against intracellular C. trachomatis. Therefore, we will define host metabolic regulation mechanisms upon mircoenvironmental factors that influence the antibiotic efficacy against C. trachomatis. On this basis new antibiotic treatment strategies to increase the effectiveness of antibiotics can be obtained to counteract possible treatment failures of C. trachomatis infections.

Key findings

Urogenital tract infections with Chlamydia trachomatis are the most prevalent bacterial sexually transmitted diseases worldwide. C. trachomatis recurrent or persistent infections can lead to serious sequelae such as pelvic inflammatory disease (PID), ectopic pregnancy and infertility. Doxycycline and azithromycin are first-line drugs in treating C. trachomatis infection. However, treatment failures occur in around 8% of the patients. The reason is not yet completely understood and we wonder what kind of bacterial and host factors associate with treatment failures. A transient form of decreased susceptibility of antibiotics in the absence of a genetic change has been described for extracellular bacteria. In this form of phenotypic resistance changes in the bacterial metabolism seem to influence the antimicrobial efficacy. Phenotypic resistance in chlamydial infection was reported in vitro in the chlamydial persistent state or under low oxygen conditions (2% O2). It was shown that C. trachomatis in these growth states is less susceptible to antibiotics. However, the mechanism of this are still poorly investigated. As an obligate-intracellular bacteria C. trachomatis have a reduced genome size harboring incomplete metabolic pathways. Therefore C. trachomatis depend on host metabolites. Certain stimuli inducing chlamydial persistence such as Interferon-gamma are associated with changes in the energy metabolism of the host cell. In addition, low oxygen conditions (hypoxia, 2% O2) influence the host cell metabolism in which they stimulated the glycolysis and production of lactate. Moreover, an increased proton production accounts for a drop in the pH value. While it has been reported that an altered pH directly affected the antibiotic efficacy against extracellular bacterial uropathogens, it is so far not known how the metabolic activity or an alteration in the pH impacts the antibiotic efficacy against intracellular C. trachomatis. Therefore, we will define host metabolic regulation mechanisms upon mircoenvironmental factors that influence the antibiotic efficacy against C. trachomatis. On this basis new antibiotic treatment strategies to increase the effectiveness of antibiotics can be obtained to counteract possible treatment failures of C. trachomatis infections.
Statusfinished
Effective start/end date01.01.1631.12.19

UN Sustainable Development Goals

In 2015, UN member states agreed to 17 global Sustainable Development Goals (SDGs) to end poverty, protect the planet and ensure prosperity for all. This project contributes towards the following SDG(s):

  • SDG 3 - Good Health and Well-being

Research Areas and Centers

  • Academic Focus: Center for Infection and Inflammation Research (ZIEL)

DFG Research Classification Scheme

  • 205-23 Reproductive Medicine, Urology

Funding Institution

  • DFG: German Research Association

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