Bacterial invasion and intracellular survival
This project focuses on the bacterial and cellular factors that play a role in the interaction of Neisseria gonorrhoeae with human cells.
N. gonorrhoeae is a human pathogen, causing sexually transmitted disease gonorrhea, which includes complications such as pelvic inflammatory disease, sterility and in rare cases disseminated gonococcal infection. During infection, N. gonorrhoeae depends on pathogenicity factors, such as Pili for the initial adhesion, Opa proteins that mediate invasion and PorBIA porin, which seems to be of special importance in disseminated infections. PorBIA porin interacts with the surface receptor SREC-I of epithelial cells and mediates bacterial invasion under low phosphate conditions. PorBIA is also transported into mitochondria during infection, where it induces mitochondrial fragmentation and membrane potential loss, contributing to cell death.
In addition to investigating the role of sphingolipid signaling in neisserial infection (joint project with Prof. Dr. Thomas Rudel), a part of our efforts is dedicated to the development of three-dimensional models of cervical, urethral and fallopian tube tissue that we will use for studies of neisserial invasion and transcytosis. This project is being conducted together with Prof. Dr. Thomas Rudel as a part of the Graduate College GRK 2157 on tissue models in infection.
Another part of our research investigates novel substances against microbial infection. We use C. trachomatis and N. gonorrhoeae infection models to test several classes of potential antibiotics, among them substances isolated from the sponge marine-associated actinomycetes, as well as the inhibitors of the macrophage infectivity potentiator (MIP). MIP is an important pathogenicity factor of N. gonorrhoeae required for neisserial survival and proliferation within human macrophages and neutrophils. Similar protein is present in Chlamydia trachomatis, an obligate intracellular human-specific pathogen causing sexually transmitted diseases and trachoma. MIP protein represents an attractive target for novel antimicrobial substances.