Regulation of the Mitochondrion-Fatty Acid Axis for the Metabolic Reprogramming of Chlamydia trachomatis during Treatment with β-Lactam Antimicrobials.

Infection with the obligate intracellular bacterium is the most common bacterial sexually transmitted disease worldwide. Since no vaccine is available to date, antimicrobial therapy is the only alternative in infection. However, changes in chlamydial replicative activity and the occurrence of chlamydial persistence caused by diverse stimuli have been proven to impair treatment effectiveness.

Elaborations on Corallopyronin A as a Novel Treatment Strategy Against Genital Chlamydial Infections.

Ascending infection causes functional damage to the fallopian tubes, which may lead to ectopic pregnancy and infertility in women. Treatment failures using the standard regimens of doxycycline and azithromycin have been observed. We tested the polyketide-derived α-pyrone antibiotic Corallopyronin A (CorA) that inhibits the bacterial DNA dependent RNA polymerase and has strong activity against various extracellular and some intracellular bacteria.

Interferon-γ interferes with host cell metabolism during intracellular Chlamydia trachomatis infection.

Interferon-γ (IFN-γ) is a central mediator of host immune responses including T-cell differentiation and activation of macrophages for the control of bacterial pathogens. Anti-bacterial mechanisms of IFN-γ against the obligate intracellular bacteria Chlamydiatrachomatis in epithelial cells have been intensively investigated in the past, focusing on cellular tryptophan depletion by an IFN-γ induced expression of the indoleamine 2, 3-deoxygenase (IDO). In this study, we could show that IFN-γ treatment caused a significant reduction of the host cell glycolysis that was accompanied by a reduction of glucose transporter-1 (GLUT1) and hypoxia inducible factor-1α (HIF-1α) expression.

Growth of Is Enhanced in Cells with Impaired Mitochondrial Function.

Effective growth and replication of obligate intracellular pathogens depend on host cell metabolism. How this is connected to host cell mitochondrial function has not been studied so far. Recent studies suggest that growth of intracellular bacteria such as is enhanced in a low oxygen environment, arguing for a particular mechanistic role of the mitochondrial respiration in controlling intracellular progeny.

Nontypeable Haemophilus influenzae (NTHi) directly interfere with the regulation of E-cadherin in lung epithelial cells.

Loss of epithelial barriers characterized by reduction of E-cadherin is a hallmark of chronic obstructive pulmonary disease (COPD). We investigated the effects of nontypeable Haemophilus influenzae (NTHi) infections, associated with acute exacerbations of chronic bronchitis, on the regulation of E-cadherin in host cells. NTHi infection decreased E-cadherin mRNA and protein-levels in lung epithelial cells.

Genomic factors related to tissue tropism in Chlamydia pneumoniae infection.

Background: Chlamydia pneumoniae (Cpn) are obligate intracellular bacteria that cause acute infections of the upper and lower respiratory tract and have been implicated in chronic inflammatory diseases. Although of significant clinical relevance, complete genome sequences of only four clinical Cpn strains have been obtained. All of them were isolated from the respiratory tract and shared more than 99% sequence identity.

The role of endoplasmic reticulum-related BiP/GRP78 in interferon gamma-induced persistent Chlamydia pneumoniae infection.

Direct interaction of Chlamydiae with the endoplasmic reticulum (ER) is essential in intracellular productive infection. However, little is known about the interplay between Chlamydiae and the ER under cellular stress conditions that are observed in interferon gamma (IFN-γ) induced chlamydial persistent infection. ER stress responses are centrally regulated by the unfolded protein response (UPR) under the control of the ER chaperone BiP/GRP78 to maintain cellular homeostasis.

Host immune responses after hypoxic reactivation of IFN-γ induced persistent Chlamydia trachomatis infection.

Genital tract infections with Chlamydia trachomatis (C. trachomatis) are the most frequent sexually transmitted disease worldwide. Severe clinical sequelae such as pelvic inflammatory disease (PID), tubal occlusion, and tubal infertility are linked to inflammatory processes of chronically infected tissues.