Differences in Host Cell Invasion and SPI-1 Expression between Salmonella enterica serovar Paratyphi A and the Non-Typhoidal Serovar Typhimurium (original) (raw)
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Infection and Immunity, 2008
Updated information and services can be found at: These include: REFERENCES http://iai.asm.org/content/76/3/1024#ref-list-1 at: This article cites 91 articles, 39 of which can be accessed free CONTENT ALERTS more» articles cite this article), Receive: RSS Feeds, eTOCs, free email alerts (when new http://journals.asm.org/site/misc/reprints.xhtml Information about commercial reprint orders: http://journals.asm.org/site/subscriptions/ Salmonella enterica serovar Typhimurium harbors five pathogenicity islands (SPI) required for infection in vertebrate hosts.
Journal of Bacteriology, 2000
HilA activates the expression of Salmonella enterica serovar Typhimurium invasion genes. To learn more about regulation of hilA, we isolated Tn5 mutants exhibiting reduced hilA and/or invasion gene expression. In addition to expected mutations, we identified Tn5 insertions in pstS, fadD, flhD, flhC, and fliA. Analysis of the pstS mutant indicates that hilA and invasion genes are repressed by the response regulator PhoB in the absence of the Pst high-affinity inorganic phosphate uptake system. This system is required for negative control of the PhoR-PhoB two-component regulatory system, suggesting that hilA expression may be repressed by PhoR-PhoB under low extracellular inorganic phosphate conditions. FadD is required for uptake and degradation of long-chain fatty acids, and our analysis of the fadD mutant indicates that hilA is regulated by a FadDdependent, FadR-independent mechanism. Thus, fatty acid derivatives may act as intracellular signals to regulate hilA expression. flhDC and fliA encode transcription factors required for flagellum production, motility, and chemotaxis. Complementation studies with flhC and fliA mutants indicate that FliZ, which is encoded in an operon with fliA, activates expression of hilA, linking regulation of hilA with motility. Finally, epistasis tests showed that PhoB, FadD, FliZ, SirA, and EnvZ act independently to regulate hilA expression and invasion. In summary, our screen has identified several distinct pathways that can modulate S. enterica serovar Typhimurium's ability to express hilA and invade host cells. Integration of signals from these different pathways may help restrict invasion gene expression during infection.
FEMS Microbiology Letters, 2011
Salmonella enterica serovar Typhi and Typhimurium are closely related serovars. However, S. Typhi, a human-specific pathogen, has 5% of genes as pseudogenes, far more than S. Typhimurium, which only has 1%. One of these pseudogenes corresponds to sopD2, which in S. Typhimurium encodes an effector protein involved in Salmonella-containing vacuole biogenesis in human epithelial cell lines, which is needed for full virulence of the pathogen. We investigated whether S. Typhi trans-complemented with the functional sopD2 gene from S. Typhimurium (sopD2 STM ) would reduce the invasion of human epithelial cell lines. Our results showed that the presence of sopD2 STM in S. Typhi significantly modified the bacterial ability to alter cellular permeability and decrease the CFUs recovered after cell invasion of human epithelial cell line. These results add to mounting evidence that pseudogenes contribute to S. Typhi adaptation to humans.
FEMS Immunology & Medical …, 2000
Induction of invasion gene transcription and expression of the invasive phenotype of Salmonella strains are regulated by environmental conditions. Experimental evidence indicates that oxygen, pH, and osmotic conditions need to closely resemble those of the host intestinal lumen for invasion gene activation. The hilA gene, encoded on Salmonella pathogenicity island 1 (SPI-1), is a transcriptional activator which is required for invasion and whose expression is modulated by oxygen, pH, and osmolarity. Additionally, hilA is regulated by genetic elements encoded on SPI-1 (hilC/sirC/sprA and hilD), as well as by elements which reside outside of SPI-1 (phoP/phoQ and sirA), although how environmental signals modulate hilA is unknown. In an effort to further characterize the Salmonella invasion gene regulon, we have created and preliminarily characterized 18 Tn5 insertions which result in upregulation of a hilA: :lacZY fusion. We have classified the mutations based on location and phenotype into three classes. Six class 1 and six class 2 mutants have insertions in SPI-1 near the invasion gene orgA or the invasion gene regulator hilD, respectively. Six class 3 mutants reside outside of SPI-1 in four different loci. The class 2 and 3 mutations induce overexpression of an episomal hilA: :lacZY fusion and significantly increase S. typhimurium invasion of HEp-2 cells in a standard invasion assay. These data implicate new regions of SPI-1 as being involved in the regulation of invasion by S. typhimurium and identify new invasion gene regulators located outside of SPI-1.
Cellular Microbiology, 2002
Type III secretion systems (TTSS) are used by Gramnegative pathogens to translocate proteins into eukaryotic host cells. Salmonella enterica serovar Typhimurium (S. Typhimurium) has two of these specialized systems, which are encoded on separate Salmonella pathogenicity islands (SPI-1 and SPI-2) and translocate unique sets of effectors. The specific roles of these systems in Salmonella pathogenesis remain undefined, although SPI-1 is required for bacterial invasion of epithelial cells and SPI-2 for survival/replication in phagocytic cells. However, because SPI-1 TTSS mutants are invasionincompetent, the role of this TTSS in post-invasion processes has not been investigated. In this study, we have used two distinct methods to internalize a noninvasive SPI-1 TTSS mutant (invA) into cultured epithelial cells: (i) co-internalization with wild-type S. Typhimurium (SPI-1-dependent) and (ii) complementation with the Yersinia pseudotuberculosis invasin (inv) gene (SPI-1-independent). In both cases, internalized invA mutants were unable to replicate intracellularly, indicating that SPI-1 effectors are essential for this process and cannot be complemented by wild-type bacteria in the same cell. Analysis of the biogenesis of SCVs showed that vacuoles containing
Role of antigens and virulence factors of Salmonella enterica serovar Typhi in its pathogenesis
Salmonella enterica serovar Typhi (S. Typhi), the aetiologic agent of typhoid fever, is a human restricted pathogen. The molecular mechanism of Salmonella pathogenicity is complex. The investigations of the molecular mechanisms of Salmonella virulence factors have shown that pathogenic Salmonella spp. are distinguished from their non-pathogenic relatives by the presence of specific pathogenicity genes, often organized in so-called pathogenicity islands (PIs). The type III secretion system (T3SS) proteins encoded by two Salmonella PIs (SPIs) are associated with the pathogenicity at molecular level. The identification of T3SS has provided new insight into the molecular factors and mechanisms underlying bacterial pathogenesis. The T3SS encoded by SPI-1 contains invasion genes; while SPI-2 is responsible for intracellular pathogenesis and has a crucial role for systemic S. enterica infections. These studies reveal a complex set of pathogenic interferences between intracellular Salmonella and its host cells. The understanding of the mechanisms by which Salmonella evade the host defense system and establish pathogenesis will be important for proper disease management.
Flagellin is required for host cell invasion and normal SPI-1 expression by Salmonella Paratyphi A
Infection and Immunity, 2015
Salmonella entericaserovar Paratyphi A is a human-specific serovar that, together withSalmonella entericaserovar Typhi andSalmonella entericaserovar Sendai, causes enteric fever. Unlike the nontyphoidalSalmonella entericaserovar Typhimurium, the genomes ofS. Typhi andS. Paratyphi A are characterized by inactivation of multiple genes, including in the flagellum-chemotaxis pathway. Here, we explored the motility phenotype ofS. Paratyphi A and the role of flagellin in key virulence-associated phenotypes. Motility studies established that the human-adapted typhoidalS. Typhi,S. Paratyphi A, andS. Sendai are all noticeably less motile thanS. Typhimurium, and comparative transcriptome sequencing (RNA-Seq) showed that inS. Paratyphi A, the entire motility-chemotaxis regulon is expressed at significantly lowers levels than inS. Typhimurium. Nevertheless,S. Paratyphi A, likeS. Typhimurium, requires a functional flagellum for epithelial cell invasion and macrophage uptake, probably in a motili...
Infection and Immunity, 2005
An important step in Salmonella enterica serovar Typhimurium virulence is the ability to invade the intestinal epithelium. The invasion process requires a large number of genes encoded on Salmonella pathogenicity island 1 (SPI-1) at centisome 63 as well as genes located in other positions throughout the chromosome. Expression of the invasive phenotype is tightly regulated by environmental cues that are processed by a complex regulatory scheme. A central player in the invasion regulatory pathway is the HilA protein, which is transcriptional activator belonging to the OmpR/ToxR family. A number of positive regulators ( hilC , hilD , fis , sirA / barA , csrAB , phoBR , fadD , envZ / ompR , and fliZ ) and negative regulators ( hha , hilE , lon , ams , phoP c and pag ) have been identified that are able to alter expression of hilA transcription. Recent work has found that hilA transcription requires the HilD protein for activation. Other work has emphasized the importance of HilE as a ne...
BMC Microbiology
Background Salmonella enterica serovar Typhimurium is an intestinal pathogen capable of infecting a wide range of animals. It initiates infection by invading intestinal epithelial cells using a type III secretion system encoded within Salmonella pathogenicity island 1 (SPI-1). The SPI-1 genes are regulated by multiple interacting transcription factors. The master regulator is HilD. HilE represses SPI-1 gene expression by binding HilD and preventing it from activating its target promoters. Previous work found that acetate and nutrients synergistically induce SPI-1 gene expression. In the present study, we investigated the role of HilE, nominally a repressor of SPI-1 gene expression, in mediating this response to acetate and nutrients. Results HilE is necessary for activation of SPI-1 gene expression by acetate and nutrients. In mutants lacking hilE, acetate and nutrients no longer increase SPI-1 gene expression but rather repress it. This puzzling response is not due to the BarA/SirA...