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Salmonella are facultative intracellular Gram-negative bacteria that are found ubiquitously in nature and have the ability to infect a wide range of hosts including humans, domesticated, wild mammals, and birds. The principal clinical manifestations associated with Salmonella infection in humans are enteric fever (typhoid and paratyphoid) and a self-limiting gastroenteritis (salmonellosis). Additionally, silent carriage of this bacterium is frequent and contributes to disease dissemination. Typhoid fever still represents a major public health problem in many developing countries. On the other hand, industrialized countries experience an increased incidence of nontyphoidal Salmonella infections with most cases tracing back to food contamination. Studies using mouse model of infection with a highly virulent Salmonella typhimurium serotype have provided important insight into the complexity of the innate immune response to infection. The players are numerous but emphasis was placed on the genes that were discovered using genetic approaches and in vivo assay with live pathogen and include positional cloning of mouse mutations and manipulation of genes in the context of whole animal either by transgenesis or knockout technologies. Some of the critical genes include those known to play a role in the detection of the bacteria (Cd14, Lbp, Tlr4 and Tlr5) and in microbicidal activity (Slc11a1, Nos2, NADPH oxidase and cryptdins). These discoveries have already initiated the search for the contribution of particular genetic pathways in the innate immune response of humans to infection with Salmonella and other intracellular microorganisms.  相似文献   

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Bioinformatics is a central discipline in modern life sciences aimed at describing the complex properties of living organisms starting from large-scale data sets of cellular constituents such as genes and proteins. In order for this wealth of information to provide useful biological knowledge, databases and software tools for data collection, analysis and interpretation need to be developed. In this paper, we review recent advances in the design and implementation of bioinformatics resources devoted to the study of metals in biological systems, a research field traditionally at the heart of bioinorganic chemistry. We show how metalloproteomes can be extracted from genome sequences, how structural properties can be related to function, how databases can be implemented, and how hints on interactions can be obtained from bioinformatics.  相似文献   

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