Neisseria gonorrhoeae is an obligate human specific pathogenic bacterium that causes the sexually transmitted disease, gonorrhea. Gonococci have the capacity to constantly change their surface creating millions of antigenically different bacteria in a given population. This diplococcus preferentially colonizes the mucosal surface of the male urethra and the female cervix. In most cases, gonococci cause local inflammation but also may spread within the host to cause systemic infections leading to serious conditions such as arthritis, endocarditis, meningitis, and pneumonia. To cause systemic infection, bacteria have to cross the epithelial barrier by transmigration or by destructing the epithelial cells. Once the bacteria reach the subepithelial layer and the blood stream they have to adapt to these niches in order to disseminate to other tissue. We investigate the molecular basis of disseminating gonococcal infection (DGI) with a focus on the bacterial factors required for dissemination and adaptation as well as the response of the host cell to these hypervariable bacteria. In a further research topic we investigate the role of gonococcal non-coding RNAs in controlling gene expression and antigenic variation.
Mechanisms of disseminating gonococcal infection
N. gonorrhoeae express numerous variant surface proteins mediating adherence to and invasion into target cells. Bacteria expressing the major outer membrane porin of serotype A (PorBIA) is frequently isolated from patients with severe disseminating infections. PorB of this serotype triggers invasion into various host cells also in the absence of any other adhesin or invasin. PorBIA-mediated interaction, however, depends on an environment as it is found in serum. Host cell invasion of PorBIA-expressing gonococci occurs by engagement of EGF-repeat containing class F scavenger receptor, SREC (scavenger receptors expressed on endothelial cells). However, the host cell senses the interacting bacteria and responds with the release of ‘danger signal’ molecules like Gp96 which prevent the invasion of the pathogen. We are just starting to understand the complex interplay between pathogen and host. This project focusses on the role of sphingolipids in gonococcal infection (read more) and the identification of additional bacterial factors required for disseminating gonococcal infection (read more).
Regulatory RNA in gonococcal infection
In recent years non-coding (nc) RNAs which act as post-transcriptional regulators in gene expression control were increasingly recognized as important components of regulatory networks in bacteria. Detection of ncRNAs has been boosted by the development of high-throughput RNA sequencing (RNA-seq) techniques and, not surprisingly, a considerable number of putative trans-acting small regulatory RNAs (sRNAs) and cis-acting antisense RNAs (asRNAs) was identified in the transcriptome of Neisseria gonorrhoeae. This project investigates the role of gonococcal ncRNAs in bacterial metabolism and Neisseria host interaction (read more).