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IS-DAAD-Forskerutveksl. Norge-Tyskland

Analysis of the lipopolysaccharide-mediated function of Salmonella adhesins in the presence of bacteriophages

Awarded: NOK 79,281

Gram-negative bacteria are major pathogens to combat, especially as already resistances to last resort antibiotics of the carbapenem class have occurred. Their outer membrane consists of a lipopolysaccharide (LPS)-phospholipid heterobilayer. Bacteriophages can use LPS as receptor that triggers particle opening and DNA release as first steps of infection cycle. Moreover, outer membrane proteins (Omps) with beta-barrel structure are wide-spread phage receptors. However, despite their importance for phage-based antibiotic therapy, particle opening mechanisms after contact with the membrane receptors are not well understood. Moreover, the influence of Omps on the physicochemical properties of LPS in the membrane has not been studied, nor whether LPS interaction is important for the function of membrane-embedded proteins. Yet, a few recent studies propose that the dynamic turnover and mobility of LPS at the outer membrane are protein dependent. Salmonella enterica serovar Typhimurium (S. Typhimurium) causes gastrointestinal infection and other invasive diseases that affect millions of people every year. Salmonella spp. expresses a remarkable amount of adhesins targeting the extracellular matrix (ECM), crucial for infection and colonization of Salmonella to epithelial cells in the urethral and intestinal tract of animals. These adhesins are proteins anchored in the outer membrane via Omp-like domains suggesting that they may function in an LPS-dependent manner. Taken together, LPS is a key receptor for phages, and a key molecule influencing bacterial adhesion functions. Understanding the underlying binding mechanisms is key to developing novel therapies. The aim of this project is to bring together complementary expertise on LPS effects, including very complementary research methods, to build a sustainable international collaboration for future, high-profile grant applications.

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IS-DAAD-Forskerutveksl. Norge-Tyskland