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The mammalian host has a number of innate immune mechanisms designed to limit the spread of infection, yet many bacteria, including Salmonella, can cause systemic disease. Salmonella typhimurium-infected phagocytes traverse the gastrointestinal (GI) epithelium and enter the bloodstream within minutes after ingestion, thereby spreading throughout its host. Here, we provide a cellular and molecular basis for this phenomenon. We demonstrate that S. typhimurium manipulates the migratory properties of infected GI phagocytes with a type III secretion system. We show that one secreted effector, SrfH, interacts with the host protein TRIP6, a member of the zyxin family of adaptor proteins that regulate motility. SrfH promotes phagocyte motility in vitro and accelerates the systemic spread of infection away from the lumen of the intestine in the mouse. This is a previously uncharacterized mechanism by which an intracellular pathogen overcomes host defenses designed to immobilize infected cells. bacteremia | secreted effector | TRIP6 | type 3 secretion | virulence

Research has been conducted on the Salmonella enterica genome. The authors hypothesized that SdiA was used to detect the signals of the other bacterial species and the results of the test of this hypothesis are reported.

Research was conducted to examine the hypothesis that the virulence plasmid of Salmonella typhimurium strains, LT2, 14028 and SR-11, is self-transmissible while the plasmid of strain SL1344 is not. Filter matings on M9 minimal glucose plates with a recipient strain lacking the virulence plasmid is required in optimal conjugation frequency. Results indicate that matings reduce efficiency by up to 400-fold.

Escherichia and Salmonella diverged in their evolution from a common ancestor some 100 to 160 mil years ago but the relative order of the genes in their chromosomes has been conserved. The intergenic region between smpB and nrdE of the Salmonella enterica chromosome is analyzed using restriction fragment length polymorphism studies and Southern blotting techniques to determine the genetic architecture of this segment. Results indicate that the mosaic structure of this region was brought about by multiple insertions and deletions during the evolutionary development of the organism.

Research was conducted to describe IroN, a novel outer membrane siderophore receptor characteristic of Salmonella enterica. The gene is located downstream of the IroBC operon in the iroA locus of Salmonella enterica serotype Typhi. Mutational analysis of the gene in S. enterica and expression in E. coli identified a 78-kDa outer membrane protein as the iroN gene product. Results indicate that the iroA locus functions in iron acquisition in S. enterica.

The Salmonella typhimurium SdiA homolog was cloned and a systematic screen was implemented on the sdiA-controlled genes. Findings from the analysis of the sequencing of a 4.4-kb fragment, which encodes the S. typhimurium sdiA gene, revealed that the fragment encodes the 5' end UvrC, all of SdiA and SirA and the 3' end of YecC. The S. typhimurium sdiA gene was also found to weakly support the E. coli sdiA gene for suppression of filamentation and for activation of ftsQAZ at promoter 2 due to an ftsZ(Ts) allele.

The distribution of fimbrial operons among two Salmonella serotypes with distant phylogenetic relationships was analyzed to determine the role of horizontal gene transfer and deletion in the development of the fimbrial operons. Genetic analysis of Salmonella enterica serotypes indicated the limited phylogenetic expression of the sef and lbf operons which were characterized as recent acquisitions by the two distantly related serotypes. Furthermore, the acquisition of specific fimbrial operons served as one of the mechanisms that enabled Salmonella serotypes to expand their host range.

Phagocytic cells are a critical line of defense against infection. The ability of a pathogen to survive and even replicate within phagocytic cells is a potent method of evading the defense mechanisms of the host. A number of pathogens survive within macrophages after phagocytosis and this contributes to their virulence. Salmonella is one of these pathogens. Here we report that 6-14 hr after Salmonella enters the macrophage and replicates, it resides in large vacuoles and causes the destruction of these cells. Furthermore, we identified four independently isolated MudJ-lacZ insertion mutants that no longer cause the formation of these vacuoles or kill the macrophages. All four insertions were located in the ompR/envZ regulon. These findings suggest that killing and escape from macrophages may be as important steps in Salmonella pathogenesis as are survival and replication in these host cells.

A study was conducted on the role of the Salmonella typhimurium fimbrial operon lpfABCDE in the colonization of murine Peyer's patches. in vitor adhession assay, virulence studies, recombinant DNA techniques and electron microscopy were performed. Results showed that lpfABCDE participates in adhesion to murine Peyer's patches. Lpf-mediated adhesion apparently resulted in binding only specific areas of the alimentary tract.

Transposon mutagenesis generated transcriptional fusions were isolated and Fur titration assays were performed on a plasmid gene bank to identify Fur regulon or iron-regulated genes in Salmonella typhimurium. The methods were both successful with the first finding seven Fur-regulated insertions and the second eight Fur-regulated promoters. The assay method was easier and allowed for immediate sequence analysis while mutagenesis allowed for the analysis of more loci. Eleven genes with known homologs were identified while three Fur regulon indicated areas that were not known to be Fur regulated.

A new fimbrial operon encoding a fimbrial operon and containing five genes named lpfABCDE, has been identified at 78 min on the Salmonella typhimurium chromosome by hybridization. The lpf operon is related to the fim operon encoding 1 fimbriae of Salmonella typhimurium in terms of conservation of the amino acid sequence and gene order. The lpf gene cluster does not contain any gene encoding regulator proteins.

A 63-kb nucleotide fragment of the Salmonella typhimurium ethanolamine utilization operon codes for six complete open reading frames eutJ, eutH, eutG, cchB, cchA and eutE. eutI codes for an enzyme that resembles phosphate acetyltransferase, while EutE and EutG proteins resemble the AdhE sequence of Escherichia coli alcohol dehydrogenase. Mutants resulting from eutE or eutG mutations are incapable of utilizing ethanolamine as a carbon source and exhibit reduced utilization of the same as a nitrogen source. CchA and CchB proteins contribute to the generation of intracellular microcompartments for ethanolamine metabolism.

Screening procedures for hemolysis on blood agar established a Salmonella gene encoding a cytolysin. It has no association with other hemolysins or toxins. Virulence and Salmonella survival inside mouse peritoneal macrophages depend on the toxin, as indicated by the median lethal dose and infection kinetics in mice.

Two-dimensional proton nuclear magnetic resonance spectroscopy was used to study the labile protons of two 32-base-pair, four-arm models of immobile Holliday junctions. Complete resonance assignments were obtained by slow exchange between imino and cytosineamino protons. All four arms of both Holliday junctions possessed base-pairing up to and including the junction point. Moreover, arm stacking geometries were opposite for the two junctions studied.

An investigation was conducted to identify Salmonella typhimurium genes involved in resistance to host antimicrobial peptides. The procedure involved the screening of a mutant library for clones hypersensitive to protamine. The sreening isolated several mutants falling in different phenotypic classes with respect to susceptibility to different antimicrobial agents. The resistance loci were mapped to eight unlinked locations in the chromosome. In addition, some mutants were associated with defective lipopolysaccharide and phoP, a virulence gene regulator. These results demonstrate the complexity of peptide resistance and its association with virulence.

The phoP gene of Salmonella typhimurium is involved in the transcriptional regulation of genes involved in virulence and survival. By screening a library of Escherichia coli clones, the phoP gene of E. coli was isolated and charactrized. The E. coli phoP gene was mapped to 25 minutes in the E. coli chromosome adjacent to the purB locus. Sequence data showed that the E. col PhoP is 98% similar to the Salmonella PhoP. Studies on phoP mutants showed that the gene is involved in response to stress situations such as nutrient deprivation and exposure to toxins.

THE REPAIR OF DNA DAMAGE Requires the coordination of a large number of gene products [1]. For example, in responding to ultraviolet (UV) irradiation, cells can use photoreactivation or excision [...]

Induction of Salmonella Stress Proteins upon Infection of Macrophages COORDINATED REGULATION OF genes necessary for virulence enables a pathogen to respond to diverse conditions and environments encountered during the infectious [...]

A Salmonella Locus That Controls Resistance to Microbicidal Proteins from Phagocytic Cells PROFESSIONAL PHAGOCYTIC CELLS are important in the body's defense against pathogenic microorganisms; they engulf and kill invading microbes [...]

Epithelial Cell Surfaces Induce Salmonella Proteins Required for Bacterial Adherence and Invasion SALMONELLOSIS IS A MAJOR HEALTH problem throughout the world. In the United states this disease accounts for 40,000 [...]