Salmonella enterica serovar Enteritidis colonization of the chicken caecum requires the HilA regulatory protein

Bohez, Lotte; Ducatelle, Richard; Pasmans, Frank; Botteldoorn, Nadine; Haesebrouck, Freddy; Immerseel, Filip Van

doi:10.1016/j.vetmic.2006.03.007

Cited by 50 publications

(29 citation statements)

References 38 publications

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“…We chose to use a high dose for oral challenge of chickens, unlike what the birds would encounter in a natural setting, since we observed very low levels of colonization at lower doses (data not shown), making it difficult to interpret the data. In addition, other groups have also used high challenge doses in chicken experiments (3,13,32), thus validating our findings.…”

Section: Discussionsupporting

confidence: 86%

“…We chose to construct deletion mutants in SPI-1 since it has been well documented that the SPI-1 T3SS is essential for the secretion of effector proteins and plays an important role in infection in different animal models (3,4,43,52). Thus, it would be expected that deletion of the pathogenicity island in its entire form or the knockout of certain individual genes would not allow the bacterium to form a fully functional T3SS apparatus or to secrete any of the SPI-1 related effectors in order to cause intestinal invasion and facilitate bacterial uptake.…”

Section: Discussionmentioning

confidence: 99%

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Salmonella enterica Serovar Enteritidis Pathogenicity Island 1 Is Not Essential for but Facilitates Rapid Systemic Spread in Chickens

et al. 2009

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Salmonella enterica subsp. enterica serovar Enteritidis is a leading cause of human food-borne illness that is mainly associated with the consumption of contaminated poultry meat and eggs. To cause infection, S. Enteritidis is known to use two type III secretion systems, which are encoded on two salmonella pathogenicity islands, SPI-1 and SPI-2, the first of which is thought to play a major role in invasion and bacterial uptake. In order to study the role of SPI-1 in the colonization of chicken, we constructed deletion mutants affecting the complete SPI-1 region (40 kb) and the invG gene. Both ⌬SPI-1 and ⌬invG mutant strains were impaired in the secretion of SipD, a SPI-1 effector protein. In vitro analysis using polarized human intestinal epithelial cells (Caco-2) revealed that both mutant strains were less invasive than the wild-type strain. A similar observation was made when chicken cecal and small intestinal explants were coinfected with the wild-type and ⌬SPI-1 mutant strains. Oral challenge of 1-week-old chicken with the wild-type or ⌬SPI-1 strains demonstrated that there was no difference in chicken cecal colonization. However, systemic infection of the liver and spleen was delayed in birds that were challenged with the ⌬SPI-1 strain. These data demonstrate that SPI-1 facilitates systemic infection but is not essential for invasion and systemic spread of the organism in chickens.

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Section: Discussionsupporting

confidence: 86%

Section: Discussionmentioning

confidence: 99%

Salmonella enterica Serovar Enteritidis Pathogenicity Island 1 Is Not Essential for but Facilitates Rapid Systemic Spread in Chickens

et al. 2009

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“…In addition, earlier work showed that SPI-1 marginally contributed to systemic localization (26). Moreover, deletion of the hilA SPI-1 activator reduced localization to systemic organs early during infection but not at a later time point (52). These results, in combination with our gene regulation data, suggest that SPI-1 may be important early in infection before the body temperature of birds has plateaued at ϳ42°C.…”

Section: Discussionsupporting

confidence: 81%

Poultry Body Temperature Contributes to Invasion Control through Reduced Expression of Salmonella Pathogenicity Island 1 Genes in Salmonella enterica Serovars Typhimurium and Enteritidis

Troxell

Petri

Daron

et al. 2015

Appl Environ Microbiol

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b Salmonella enterica serovars Typhimurium (S. Typhimurium) and Enteritidis (S. Enteritidis) are foodborne pathogens, and outbreaks are often associated with poultry products. Chickens are typically asymptomatic when colonized by these serovars; however, the factors contributing to this observation are uncharacterized. Whereas symptomatic mammals have a body temperature between 37°C and 39°C, chickens have a body temperature of 41°C to 42°C. Here, in vivo experiments using chicks demonstrated that numbers of viable S. Typhimurium or S. Enteritidis bacteria within the liver and spleen organ sites were >4 orders of magnitude lower than those within the ceca. When similar doses of S. Typhimurium or S. Enteritidis were given to C3H/HeN mice, the ratio of the intestinal concentration to the liver/spleen concentration was 1:1. In the avian host, this suggested poor survival within these tissues or a reduced capacity to traverse the host epithelial layer and reach liver/spleen sites or both. Salmonella pathogenicity island 1 (SPI-1) promotes localization to liver/spleen tissues through invasion of the epithelial cell layer. Following in vitro growth at 42°C, SPI-1 genes sipC, invF, and hilA and the SPI-1 rtsA activator were downregulated compared to expression at 37°C. Overexpression of the hilA activators fur, fliZ, and hilD was capable of inducing hilA-lacZ at 37°C but not at 42°C despite the presence of similar levels of protein at the two temperatures. In contrast, overexpression of either hilC or rtsA was capable of inducing hilA and sipC at 42°C. These data indicate that physiological parameters of the poultry host, such as body temperature, have a role in modulating expression of virulence. Salmonella enterica serovars Typhimurium (S. Typhimurium) and Enteritidis (S. Enteritidis) are major causes of foodborne diseases worldwide. In the United States, S. Typhimurium and S. Enteritidis accounted for the majority of confirmed cases of Salmonella outbreaks between 1970 and 2011 (1). These two are nontyphoid Salmonella (NTS) serovars that are capable of causing disease signs in a variety of animals, which contrasts with typhoid fever serovars that exclusively infect humans. Numerous food products have been associated with Salmonella outbreaks and illnesses in humans; however, poultry products are frequently implicated in outbreaks associated with NTS (www.cdc.gov /Salmonella/outbreaks.html). In 2010, a major poultry-related outbreak occurred that involved S. Enteritidis infections across 11 states and resulted in the recall of 380 million eggs (2).S. Typhimurium invades the host epithelial cell layer and migrates to liver and spleen tissue sites through the action of a type 3 secretion system (T3SS), encoded by Salmonella pathogenicity island 1 (SPI-1). SPI-1 is a DNA segment that is approximately 40 kb in size and encodes the structural components of the secretion system, secreted and chaperone proteins, and transcription factors that activate expression of the SPI-1 genes (3-5). Three regulators that are carried wi...

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“…Furthermore, both SPI-4 and SPI-1 genes are downregulated during infection of macrophages (30). However, whereas HilA is involved in the invasion of a broad range of hosts (e.g., chickens [9], cattle [83], and pigs [11]), SPI-4 was shown to be important for the colonization of cattle but not of chickens (61,62). Possibly additional regulatory effects control this host specificity.…”

Section: Discussionmentioning

confidence: 99%

Delineation of the Salmonella enterica Serovar Typhimurium HilA Regulon through Genome-Wide Location and Transcript Analysis

et al. 2007

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The Salmonella enterica serovar Typhimurium HilA protein is the key regulator for the invasion of epithelial cells. By a combination of genome-wide location and transcript analysis, the HilA-dependent regulon has been delineated. Under invasion-inducing conditions, HilA binds to most of the known target genes and a number of new target genes. The sopB, sopE, and sopA genes, encoding effector proteins secreted by the type III secretion system on Salmonella pathogenicity island 1 (SPI-1), were identified as being both bound by HilA and differentially regulated in an HilA mutant. This suggests a cooperative role for HilA and InvF in the regulation of SPI-1-secreted effectors. Also, siiA, the first gene of SPI-4, is both bound by HilA and differentially regulated in an HilA mutant, thus linking this pathogenicity island to the invasion key regulator. Finally, the interactions of HilA with the SPI-2 secretion system gene ssaH and the flagellar gene flhD imply a repressor function for HilA under invasion-inducing conditions. Salmonella enterica serovar Typhimurium causes a host-dependent range of diseases from self-limiting gastroenteritis to life-threatening systemic infections. The complex infection process is initiated by invasion of the intestinal epithelial monolayer (75) by means of a type III secretion system (TTSS), encoded on pathogenicity island 1 (SPI-1), through which effector proteins are translocated into the epithelial cells (17,53). By manipulating host cell functions via these effector proteins, S. enterica serovar Typhimurium alters the epithelial cell's cytoskeletal structure, leading to bacterial internalization (76).The key regulator for the composition and functioning of this invasion-enabling TTSS and associated effector proteins is HilA, an OmpR/ToxR family transcriptional regulator (5), which is also encoded within SPI-1. A complex interaction of environmental and genetic control elements (3,29,43) induces HilA to activate the inv/spa and prg operons, encoding components of the TTSS apparatus (51, 52), and the sic/sip operon, encoding a chaperone and secreted proteins (23). SPI-4, which is required for the enteric phase of pathogenesis (62), also has been related to HilA (2, 23, 61). Furthermore, HilA represses its own expression (23). In addition, HilA indirectly regulates expression of secreted proteins by activating the transcription of the SPI-1 invF gene, encoding an AraC family transcriptional regulator (19).In this work, data on in vivo HilA binding, obtained through genome-wide location analysis (GWLA) or chromatin immunoprecipitation microarray (CHIP-chip) experiments (12), have been combined with transcriptional profiling of an hilA mutant versus a wild-type strain and in silico motif detection to provide a delineation of the direct HilA regulon, i.e., all genes directly bound by HilA, on a genome-wide scale. Retrieval of most of the known direct HilA target genes validated this approach. Moreover, a number of new targets were identified. Based on these findings, an extension of the ...

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Salmonella enterica serovar Enteritidis colonization of the chicken caecum requires the HilA regulatory protein

Cited by 50 publications

References 38 publications

Salmonella enterica Serovar Enteritidis Pathogenicity Island 1 Is Not Essential for but Facilitates Rapid Systemic Spread in Chickens

Salmonella enterica Serovar Enteritidis Pathogenicity Island 1 Is Not Essential for but Facilitates Rapid Systemic Spread in Chickens

Poultry Body Temperature Contributes to Invasion Control through Reduced Expression of Salmonella Pathogenicity Island 1 Genes in Salmonella enterica Serovars Typhimurium and Enteritidis

Delineation of the Salmonella enterica Serovar Typhimurium HilA Regulon through Genome-Wide Location and Transcript Analysis

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