scholarly journals Salmonella enterica Serovar Typhimurium Exploits Toll-Like Receptor Signaling during the Host-Pathogen Interaction

2009 ◽  
Vol 77 (11) ◽  
pp. 4750-4760 ◽  
Author(s):  
Christine E. Wong ◽  
Subash Sad ◽  
Brian K. Coombes
Keyword(s):  
Immune System ◽  
Type Iii Secretion ◽  
Innate Immune System ◽  
Salmonella Enterica ◽  
Type Iii Secretion System ◽  
Secretion System ◽  
Innate Immune ◽  
Type Iii ◽  
Infection Dynamics ◽  
Serovar Typhimurium

ABSTRACT Salmonella survives and replicates in host cells by using a type III secretion system to evade host immune defenses. The innate immune system plays an important role as a first line of defense against pathogens and is mediated in part by Toll-like receptors (TLRs); however, the infection dynamics of Salmonella enterica serovar Typhimurium within macrophages stimulated with TLR ligands is poorly understood. We studied the infection dynamics of Salmonella in murine macrophages previously exposed to TLR ligands and report that treatment of macrophages with four different TLR agonists resulted in their increased phagocytic capacity toward Salmonella but not fluorescent microspheres. Further analysis revealed that the intracellular replication of Salmonella was enhanced in TLR-stimulated macrophages in a manner requiring a functional type III secretion system and enhanced transcriptional activity of the sseA virulence gene operon. Studies of mice that normally resolve an acute primary infection with Salmonella revealed that pretreatment of animals with CpG DNA had a detrimental effect on disease outcome. CpG-treated mice infected with Salmonella all succumbed to infection and had higher bacterial loads in the spleen than did control animals. These data suggest that Salmonella can exploit macrophages activated via the innate immune system for increased intracellular survival.

Safety and immunogenicity of attenuated Salmonella enterica serovar Typhimurium delivering an HIV-1 Gag antigen via the Salmonella Type III secretion system

Vaccine ◽  
2006 ◽  
Vol 24 (37-39) ◽  
pp. 6216-6224 ◽  
Author(s):  
Camille N. Kotton ◽  
Alexander J. Lankowski ◽  
Nathaniel Scott ◽  
David Sisul ◽  
Li Mei Chen ◽  
...  
Keyword(s):  
Type Iii Secretion ◽  
Salmonella Enterica ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Type Iii Secretion System ◽  
Secretion System ◽  
Type Iii ◽  
Serovar Typhimurium ◽  
Hiv 1

scholarly journals Accelerated Type III Secretion System 2-Dependent Enteropathogenesis by a Salmonella enterica Serovar Enteritidis PT4/6 Strain

2009 ◽  
Vol 77 (9) ◽  
pp. 3569-3577 ◽  
Author(s):  
Mrutyunjay Suar ◽  
Balamurugan Periaswamy ◽  
Pascal Songhet ◽  
Benjamin Misselwitz ◽  
Andreas Müller ◽  
...  
Keyword(s):  
Type Iii Secretion ◽  
Salmonella Enterica ◽  
Alternative Pathway ◽  
Type Iii Secretion System ◽  
Secretion System ◽  
Mucosal Inflammation ◽  
Classical Pathway ◽  
Type Iii ◽  
Serovar Typhimurium

ABSTRACT Salmonella enterica subsp. I serovars Typhimurium and Enteritidis are major causes of enteric disease. The pathomechanism of enteric infection by serovar Typhimurium has been studied in detail. Serovar Typhimurium employs two pathways in parallel for triggering disease, i.e., the “classical” pathway, triggered by type III secretion system 1 (TTSS-1), and the “alternative” pathway, mediated by TTSS-2. It had remained unclear whether these two pathways would also explain the enteropathogenesis of strains from other serovars. We chose the isolate P125109 of the epidemic serovar Enteritidis PT4/6, generated isogenic mutants, and studied their virulence. Using in vitro and in vivo infection experiments, a dendritic cell depletion strategy, and MyD88−/− knockout mice, we found that P125109 employs both the “classical” and “alternative” pathways for triggering mucosal inflammation. The “classical” pathway was phenotypically similar in serovar Typhimurium strain SL1344 and in P125109. However, the kinetics of the “alternative” pathway differed significantly. Via TTSS-2, P125109 colonized the gut tissue more efficiently and triggered mucosal inflammation approximately 1 day faster than SL1344 did. In conclusion, our data demonstrate that different Salmonella spp. can differ in their capacity to trigger mucosal inflammation via the “alternative” pathway in vivo.

scholarly journals Cytosporone B, an Inhibitor of the Type III Secretion System of Salmonella enterica Serovar Typhimurium

2013 ◽  
Vol 57 (5) ◽  
pp. 2191-2198 ◽  
Author(s):  
Jianfang Li ◽  
Chao Lv ◽  
Weiyang Sun ◽  
Zhenyu Li ◽  
Xiaowei Han ◽  
...  
Keyword(s):  
Type Iii Secretion ◽  
Salmonella Enterica ◽  
Bacterial Resistance ◽  
Type Iii Secretion System ◽  
Secretion System ◽  
Effector Proteins ◽  
Host Cells ◽  
Content Type ◽  
Type Iii ◽  
Serovar Typhimurium

ABSTRACTBacterial virulence factors have been increasingly regarded as attractive targets for development of novel antibacterial agents. Virulence inhibitors are less likely to generate bacterial resistance, which makes them superior to traditional antibiotics that target bacterial viability.Salmonella entericaserovar Typhimurium, an important food-borne human pathogen, has type III secretion system (T3SS) as its major virulence factor. T3SS secretes effector proteins to facilitate invasion into host cells. In this study, we identified several analogs of cytosporone B (Csn-B) that strongly block the secretion ofSalmonellapathogenicity island 1 (SPI-1)-associated effector proteins, without affecting the secretion of flagellar protein FliCin vitro. Csn-B and two other derivatives exhibited a strong inhibitory effect on SPI-1-mediated invasion to HeLa cells, while no significant toxicity to bacteria was observed. Nucleoid proteins Hha and H-NS bind to the promoters of SPI-1 regulator geneshilD,hilC, andrtsAto repress their expression and consequently regulate the expression of SPI-1 apparatus and effector genes. We found that Csn-B upregulated the transcription ofhhaandhns, implying that Csn-B probably affected the secretion of effectors through the Hha–H-NS regulatory pathway. In summary, this study presented an effective SPI-1 inhibitor, Csn-B, which may have potential in drug development against antibiotic-resistantSalmonella.

scholarly journals SigE Is a Chaperone for the Salmonella enterica Serovar Typhimurium Invasion Protein SigD

2001 ◽  
Vol 183 (4) ◽  
pp. 1452-1454 ◽  
Author(s):  
K. Heran Darwin ◽  
Lloyd S. Robinson ◽  
Virginia L. Miller
Keyword(s):  
Hybrid System ◽  
Type Iii Secretion ◽  
Salmonella Enterica ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Type Iii Secretion System ◽  
Secretion System ◽  
Type Iii ◽  
Serovar Typhimurium ◽  
Two Hybrid

ABSTRACT SigD is translocated into eucaryotic cells by a type III secretion system. In this work, evidence that the putative chaperone SigE directly interacts with SigD is presented. A bacterial two-hybrid system demonstrated that SigE can interact with itself and SigD. In addition, SigD was specifically copurified with SigE-His6on a nickel column.

scholarly journals Killing of Candida albicans Filaments by Salmonella enterica Serovar Typhimurium Is Mediated by sopB Effectors, Parts of a Type III Secretion System

2011 ◽  
Vol 10 (6) ◽  
pp. 782-790 ◽  
Author(s):  
Younghoon Kim ◽  
Eleftherios Mylonakis
Keyword(s):  
Type Iii Secretion ◽  
Salmonella Enterica ◽  
Critical Role ◽  
Type Iii Secretion System ◽  
Secretion System ◽  
Content Type ◽  
Type Iii ◽  
Serovar Typhimurium ◽  
Fungal Interactions

ABSTRACTAlthough bacterial-fungal interactions shape microbial virulence during polymicrobial infections, only a limited number of studies have evaluated this interaction on a genetic level. We report here that one interaction is mediated bysopB, an effector of a type III secretion system (TTSS) ofSalmonella entericaserovar Typhimurium. In these studies, we screened 10 TTSS effector-related mutants and determined their role in the killing ofC. albicansfilamentsin vitroduring coinfection in planktonic environments. We found that deleting thesopBgene (which encodes inositol phosphatase) was associated with a significant decrease inC. albicanskilling at 25°C after 5 days, similar to that caused by the deletion ofsipB(which encodes TTSS translocation machinery components). ThesopBdeletion dramatically influenced the killing ofC. albicansfilaments. It was associated with repressed filamentation in theCaenorhabditis elegansmodel ofC. albicans-S.Typhimurium coinfection, as well as with biofilm formation byC. albicans. We confirmed that SopB translocated to fungal filaments through SipB during coinfection. Using quantitative real-time PCR assays, we found that theCandidasupernatant upregulated theS.Typhimurium genes associated withC. albicanskilling (sopBandsipB). Interestingly, the sopBeffector negatively regulated the transcription ofCDC42, which is involved in fungal viability. Taken together, these results indicate that specific TTSS effectors, including SopB, play a critical role in bacterial-fungal interactions and are important toS.Typhimurium in order to selectively compete with fungal pathogens. These findings highlight a new role for TTSS ofS.Typhimurium in the intestinal tract and may further explain the evolution and maintenance of these traits.

scholarly journals In Vivo Genetic Analysis Indicates That PhoP-PhoQ and the Salmonella Pathogenicity Island 2 Type III Secretion System Contribute Independently to Salmonella enterica Serovar Typhimurium Virulence

2001 ◽  
Vol 69 (12) ◽  
pp. 7254-7261 ◽  
Author(s):  
Carmen R. Beuzón ◽  
Kate E. Unsworth ◽  
David W. Holden
Keyword(s):  
Virulence Factors ◽  
Type Iii Secretion ◽  
Salmonella Enterica ◽  
Type Iii Secretion System ◽  
Pathogenicity Island ◽  
Secretion System ◽  
Type Iii ◽  
Serovar Typhimurium

ABSTRACT Many virulence factors are required for Salmonella enterica serovar Typhimurium to replicate intracellularly and proliferate systemically within mice. In this work, we have carried out genetic analyses in vivo to determine the functional relationship between two major virulence factors necessary for systemic infection byS. enterica serovar Typhimurium: theSalmonella pathogenicity island 2 (SPI-2) type III secretion system (TTSS) and the PhoP-PhoQ two-component regulatory system. Although previous work suggested that PhoP-PhoQ regulates SPI-2 TTSS gene expression in vitro, in vivo competitive analysis of mutant strains indicates that these systems contribute independently toS. typhimurium virulence. Our results also suggest that mutation of phoP may compensate partially for defects in the SPI-2 TTSS by deregulating SPI-1 TTSS expression. These results provide an explanation for previous reports showing an apparent functional overlap between these two systems in vitro.

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