scholarly journals HilE is required for synergistic activation of SPI-1 gene expression in Salmonella enterica serovar Typhimurium

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Selwan Hamed ◽  
Riham M. Shawky ◽  
Mohamed Emara ◽  
James M. Slauch ◽  
Christopher V. Rao
Keyword(s):  
Gene Expression ◽  
Salmonella Enterica ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Growth Conditions ◽  
Intestinal Epithelial ◽  
Synergistic Activation ◽  
Wide Range ◽  
Serovar Typhimurium ◽  
In The Wild ◽  
Intestinal Pathogen

Abstract 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 two component system, which governs the response to acetate. To identify the mechanism, we profiled gene expression using RNAseq in the wild type and a ΔhilE mutant under different growth conditions. Analysis of these data suggested that the Rcs system, which regulates gene expression in response to envelope stress, is involved. Consistent with this hypothesis, acetate and nutrients were able to induce SPI-1 gene expression in mutants lacking hilE and the Rcs system. Conclusions While the exact mechanism is unknown, these results demonstrate the HilE, nominally a repressor of SPI-1 gene expression, can also function as an activator under the growth conditions investigated. Collectively, these results provide new insights regarding SPI-1 gene regulation and demonstrate that HilE is more complex than initially envisioned.

scholarly journals SlyA and HilD Counteract H-NS-Mediated Repression on the ssrAB Virulence Operon of Salmonella enterica Serovar Typhimurium and Thus Promote Its Activation by OmpR

2019 ◽  
Vol 201 (8) ◽  
Author(s):  
María M. Banda ◽  
Crispín Zavala-Alvarado ◽  
Deyanira Pérez-Morales ◽  
Víctor H. Bustamante
Keyword(s):  
Salmonella Enterica ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Growth Conditions ◽  
The Other ◽  
Regulatory Mechanisms ◽  
Two Component System ◽  
Content Type ◽  
Additive Action ◽  
Serovar Typhimurium ◽  
Bacterial Fitness

ABSTRACT H-NS-mediated repression of acquired genes and the subsequent adaptation of regulatory mechanisms that counteract this repression have played a central role in the Salmonella pathogenicity evolution. The Salmonella pathogenicity island 2 (SPI-2) is an acquired chromosomal region containing genes necessary for Salmonella enterica to colonize and replicate in different niches of hosts. The ssrAB operon, located in SPI-2, encodes the two-component system SsrA-SsrB, which positively controls the expression of the SPI-2 genes but also other many genes located outside SPI-2. Several regulators have been involved in the expression of ssrAB, such as the ancestral regulators SlyA and OmpR, and the acquired regulator HilD. In this study, we show how SlyA, HilD, and OmpR coordinate to induce the expression of ssrAB under different growth conditions. We found that when Salmonella enterica serovar Typhimurium is grown in nutrient-rich lysogeny broth (LB), SlyA and HilD additively counteract H-NS-mediated repression on ssrAB, whereas in N-minimal medium (N-MM), SlyA antagonizes H-NS-mediated repression on ssrAB independently of HilD. Interestingly, our results indicate that OmpR is required for the expression of ssrAB independently of the growth conditions, even in the absence of repression by H-NS. Therefore, our data support two mechanisms adapted for the expression of ssrAB under different growth conditions. One involves the additive action of SlyA and HilD, whereas the other involves SlyA, but not HilD, to counteract H-NS-mediated repression on ssrAB, thus favoring in both cases the activation of ssrAB by OmpR. IMPORTANCE The global regulator H-NS represses the expression of acquired genes and thus avoids possible detrimental effects on bacterial fitness. Regulatory mechanisms are adapted to induce expression of the acquired genes in particular niches to obtain a benefit from the information encoded in the foreign DNA, as for pathogenesis. Here, we show two mechanisms that were integrated for the expression of virulence genes in Salmonella Typhimurium. One involves the additive action of the regulators SlyA and HilD, whereas the other involves SlyA, but not HilD, to counteract H-NS-mediated repression on the ssrAB operon, thus favoring its activation by the OmpR regulator. To our knowledge, this is the first report involving the coordinated action of two regulators to counteract H-NS-mediated repression.

scholarly journals Salmonella enterica Serovar Typhimurium Invasion Is Repressed in the Presence of Bile

2000 ◽  
Vol 68 (12) ◽  
pp. 6763-6769 ◽  
Author(s):  
A. M. Prouty ◽  
J. S. Gunn
Keyword(s):  
Epithelial Cells ◽  
Cell Invasion ◽  
Type Iii Secretion ◽  
Salmonella Enterica ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Eukaryotic Cell ◽  
Intestinal Epithelial ◽  
Two Component System ◽  
Serovar Typhimurium ◽  
Invasive Capacity

ABSTRACT As enteric pathogens, the salmonellae have developed systems by which they can sense and adapt appropriately to deleterious intestinal components that include bile. Previously, growth in the presence of bile was shown to repress the transcription of prgH, a locus encoding components of the Salmonella pathogenicity island I (SPI-1) type III secretion system (TTSS) necessary for eukaryotic cell invasion. This result suggested an existing interaction between salmonellae, bile, and eukaryotic cell invasion. Transcription assays demonstrated that invasion gene regulators (e.g.,sirC and invF) are repressed by bile. However, bile does not interact with any of the invasion regulators directly but exerts its effect at or upstream of the two-component system at the apex of the invasion cascade, SirA-BarA. As suggested by the repression of invasion gene transcription in the presence of bile, Western blot analysis demonstrated that proteins secreted by the SPI-1 TTSS were markedly reduced in the presence of bile. Furthermore, Salmonella enterica serovar Typhimurium grown in the presence of bile was able to invade epithelial cells at only 4% of the level of serovar Typhimurium grown without bile. From these data, we propose a model whereby serovar Typhimurium uses bile as an environmental signal to repress its invasive capacity in the lumen of the intestine, but upon mucous layer penetration and association with intestinal epithelial cells, where the apparent bile concentration would be reduced, the system would become derepressed and invasion would be initiated.

scholarly journals A Nutrient-Tunable Bistable Switch Controls Motility in Salmonella enterica Serovar Typhimurium

mBio ◽  
2014 ◽  
Vol 5 (5) ◽  
Author(s):  
Santosh Koirala ◽  
Patrick Mears ◽  
Martin Sim ◽  
Ido Golding ◽  
Yann R. Chemla ◽  
...  
Keyword(s):  
Salmonella Enterica ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Phenotypic Diversity ◽  
Complex Mixture ◽  
Growth Conditions ◽  
General Mechanism ◽  
Bistable Switch ◽  
Content Type ◽  
Motile Cells ◽  
Serovar Typhimurium

ABSTRACTMany bacteria are motile only when nutrients are scarce. In contrast,Salmonella entericaserovar Typhimurium is motile only when nutrients are plentiful, suggesting that this bacterium uses motility for purposes other than foraging, most likely for host colonization. In this study, we investigated how nutrients affect motility inS. entericaand found that they tune the fraction of motile cells. In particular, we observed coexisting populations of motile and nonmotile cells, with the distribution being determined by the concentration of nutrients in the growth medium. Interestingly,S. entericaresponds not to a single nutrient but apparently to a complex mixture of them. Using a combination of experimentation and mathematical modeling, we investigated the mechanism governing this behavior and found that it results from two antagonizing regulatory proteins, FliZ and YdiV. We also found that a positive feedback loop involving the alternate sigma factor FliA is required, although its role appears solely to amplify FliZ expression. We further demonstrate that the response is bistable: that is, genetically identical cells can exhibit different phenotypes under identical growth conditions. Together, these results uncover a new facet of the regulation of the flagellar genes inS. entericaand further demonstrate how bacteria employ phenotypic diversity as a general mechanism for adapting to change in their environment.IMPORTANCEMany bacteria employ flagella for motility. These bacteria are often not constitutively motile but become so only in response to specific environmental cues. The most common is nutrient starvation. Interestingly, inSalmonella entericaserovar Typhimurium, nutrients enhance the expression of flagella, suggesting that motility is used for purposes other than foraging. In this work, we investigated how nutrients affect motility inS. entericaand found that nutrients tune the fraction of motile cells within a population. Using both experimental and mathematical analysis, we determined the mechanism governing this tunable response. We further demonstrated that the response is bistable: that is, genetically identical cells can exhibit different phenotypes under identical growth conditions. These results reveal a new facet of motility inS. entericaand demonstrate that nutrients determine not only where these bacteria swim but also the fraction of them that do so.

The effect of the Salmonella genomic island 1 on in vitro global gene expression in Salmonella enterica serovar Typhimurium LT2

2007 ◽  
Vol 9 (1) ◽  
pp. 21-27 ◽  
Author(s):  
George R. Golding ◽  
Adam B. Olson ◽  
Benoît Doublet ◽  
Axel Cloeckaert ◽  
Sara Christianson ◽  
...  
Keyword(s):  
Gene Expression ◽  
Salmonella Enterica ◽  
Genomic Island ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Global Gene Expression ◽  
Serovar Typhimurium
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