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The long range goal of Dr. Apicella's research is to understand the factors involved in the pathogenesis of human pathogenic Neisseria and nontypeable Haemophilus influenzae infections in order to develop methods to inhibit these infectious processes either by vaccination or chemotherapy. These organisms are strict human pathogens and cause considerable disease worldwide. Dr. Apicella's research combines state of the art methodologies in molecular biology, cell biology, bioinformatics and macromolecular chemistry to study mechanisms involved in bacterial pathogenesis.
The studies of the Apicella laboratory on Neisseria gonorrhoeae have shown that this organism is unique since it utilizes different mechanisms of infection in men and in women. In men, the organism is able to infect the urethral epithelial cell by the binding of the terminal lactosamine on the gonococcal lipooligosaccharide (LOS) to the asialoglycoprotein receptor on the surface of the urethral epithelial cell. This initiates a process of clathrin-dependent receptor mediated endocytosis resulting in the internalization of the gonococcus. Studies in human urethral cells from men are now focusing on the intracellular life of the gonococcus using chip array technology and proteomics to determine changes in bacterial and eukaryotic gene and protein expression as a result of this infection. Studies in women have shown that infection in cervical epithelial cells is initiated by surface ruffling induced by the interaction of the gonococcus with the complement receptor 3 (CR3) receptor on the surface of the epithelial cell. This initiates an actin-dependent process that results in the internalization of gonococci into cervical epithelial cells. Present studies are focusing on the ligand on the surface of the gonococcus that binds to CR3 and the cervical cell signaling process, which ensues. Recent studies in the Apicella Lab indicate that the gonococcus can form a biofilm during infection in patients. Studies are now underway defining the nature of this structure at the biochemical and genetic level.
The studies of the Apicella laboratory on nontypeable Haemophilus influenzae (NTHi) have shown that NTHi invades host cells by binding of the platelet-activating factor (PAF) receptor via LOS glycoforms containing phosphorylcholine (ChoP). The binding of the PAF receptor by NTHi initiates receptor coupling to a pertussis toxin-sensitive heterotrimeric G protein complex, resulting in a multifactorial host cell signal cascade and bacterial invasion. We are currently engaged in studies of NTHi biofilm formation in continuous flow chambers and during infection of airway epithelial cells. To date, these studies suggest that sialic acid plays an important role in biofilm development and gene regulation within the NTHi biofilm.
See publication list at PubMed
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