Bacterial adherence is an important event in the initiation of many infectious processes, the ability of a given bacterial strain to adhere to a mucosal or endocardial surface or endovascular foreign body is an important factor determining localization of infection. Lipotoichoic acid has been found to mediate the adherence of gram- positive cocci to epithelial cells and mucosal surfaces and to mediate the adherence of gram-positive cocci to heart valves. Lipoteichoic acid has been found to bind to fibronectin and this protein has been postulated to be the adherence site on pharyngeal epithelial cells for Streptococcus pyogenes and on heart valves covered with platelets and fibrin for endocarditis strains of gram- positive cocci. The presence or absence of fibronectin has been associated with predominance of one microorganism or the other as a colonizer of the pharynx. There have been few studies on adherence of bacteria to endovascular devices and the mechanisms for such interaction await definition. The general hypothesis of this renewal proposal is that the bacterial strain receptor surface interaction is mediated by ligands and that there are receptor sites at the receptor surface which can be defined. Once the interaction is defined, measures can be taken to prevent it from happening. In the revised renewal we plan to: 1. Determine the role of lipoteichoic acid and fibronectin on the colonization (adherence) of bacterial endocarditis strains on the rabbit endocarditis model. Animals immunized with lipoteichoic acid, or with peptidoglycan (LTA free) or non-immunized animals will be challenged with different bacterial strains. The bacterial strains will be modified with anti-lipoteichoic acid antibody, antibiotics, etc. and adherence of bacteria surface with fibronectin will be studied. The quantitation of fibronectin at the adherence site will be expanded. 2. Study adherence of strains recovered from infections located at intravenous infussion sites, including S. aureus, S. epidermidis, E. coli, K. pneumoniae and P. aeruginosa to catheter segments of different chemical composition. To study adherence after surface modification with albumin, platelet rich plasma, antibodies bone cements, etc. To define the role of different ligands including lipoteichoic acid on such adherence and of possible receptors like fibronectin as the adherence site.
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