Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0017160 (gastroenteritis)
 11,398 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The intracellular bacterial pathogen Listeria monocytogenes causes food-borne illnesses leading to gastroenteritis, meningitis or abortion. Listeria induces its internalization into some mammalian cells through binding of the bacterial surface protein InlB to its host receptor, the Met Receptor Tyrosine Kinase. InlB-induced activation of Met stimulates host signal transduction pathways that culminate in cell surface changes driving pathogen engulfment. One mammalian protein with the potential to couple Met to downstream signalling is the adaptor CrkII. CrkII contains an unusual carboxyl-terminal SH3 domain (SH3C) that promotes entry of Listeria. However, binding partners or downstream effectors of SH3C remain unknown. Here, we use RNA interference and overexpression studies to demonstrate that SH3C affects bacterial uptake, at least in part, through stimulation of host phosphatidylinositide (PI) 3-kinase. Experiments with latex beads coated with InlB protein indicated that one potential role of SH3C and PI 3 kinase is to promote changes in the F-actin cytoskeleton necessary for particle engulfment. Taken together, our results indicate that the CrkII SH3C domain engages a cellular ligand that regulates PI 3 kinase activity and host cell surface rearrangements.
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PMID:The carboxyl-terminal SH3 domain of the mammalian adaptor CrkII promotes internalization of Listeria monocytogenes through activation of host phosphoinositide 3-kinase. 1784 69

Salmonella typhimurium is a Gram-negative bacterium responsible for human diseases including gastroenteritis and typhoid fever and its quorum sensing system is currently being intensively researched. Molecular modeling and binding site analysis of SdiA homolog, a putative quorum sensor of the LuxR family and responsible for S. typhimurium pathogenecity revealed a high structural homology of their active site with three other LuxR family proteins LasR from Pseudomonas aeruginosa, TraR from Agrobacterium tumifaciens and CviR from Chromobacterium violaceum. The results show that all the LuxR family proteins harbor three conserved amino acids Tryptophan (W67) and Aspartic acid (D80) for formation of hydrogen bridges and Tyrosine (Y71) for the hydrophobic interactions (corresponding to their position in S. typhimurium SdiA) with acyl homoserine lactones (AHL)-dependent transcriptional regulators. However, in addition to the above conserved residues, Arginine (R60) also plays an important role in S. typhimurium SdiA binding with its AHL auto inducers and the complex is found to be stronger because of the interactions between nitrogen atoms of Arginine with the carbonyl oxygen in the lactone ring of AHL. The specific binding patterns would be helpful in guiding both enzymatic studies as well as design of specific inhibitors to overcome S. typhimurium pathogenecity.
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PMID:Molecular modeling and active site analysis of SdiA homolog, a putative quorum sensor for Salmonella typhimurium pathogenecity reveals specific binding patterns of AHL transcriptional regulators. 2266 Sep 44