The Salmonella pathogenicity island 13 contributes to pathogenesis in streptomycin pre-treated mice but not in day-old chickens

Elder, Jacob R.; Chiok, Kim; Paul, Narayan C.; Haldorson, Gary J.; Guard, Jean; Shah, Devendra H.

doi:10.1186/s13099-016-0098-0

Cited by 32 publications

(25 citation statements)

References 34 publications

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“…However, in that work, Espinoza et al discovered that SPI-13 does play a role in Salmonella internalization into mouse – but not human – macrophage (23). Combined with previous works showing reduced survival of IRO mutants in mice, this operon may play a more significant survival role in the context of an animal infection (19–22).…”

Section: Discussionsupporting

confidence: 55%

“…Interestingly, the IRO genes of Salmonella have been shown to be induced heavily in macrophage but not under any other condition tested, supporting a role in degrading macrophage-produced itaconate (17–19). High throughput screens have suggested that genes from this operon are important for Salmonella survival in mice (20–22). Furthermore, it has also been shown that SPI-13 is present in generalist but not human-restricted serovars of Salmonella , possibly due to reduced itaconate synthesis in human cells (23).…”

Section: Introductionmentioning

confidence: 99%

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The Salmonella LysR family regulator, RipR, activates the SPI-13 encoded itaconate degradation cluster

Hersch

Navarre

2019

Preprint

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8Itaconate is a dicarboxylic acid that is able to inhibit the isocitrate lyase enzyme of the 9 bacterial glyoxylate shunt. Activated macrophage have been shown to produce itaconate, 10 suggesting that these immune cells may employ this metabolite as a weapon against invading 11 bacteria. Here we demonstrate that itaconate can exhibit bactericidal effects under acidic 12 conditions resembling the pH of a macrophage phagosome. In parallel, successful pathogens 13 including Salmonella have acquired a genetic operon encoding itaconate degradation proteins, 14 which are induced heavily in macrophage. We characterize the regulation of this operon by the 15 neighbouring gene, itaR, in specific response to itaconate. Moreover, we develop an itaconate 16 biosensor based on the operon promoter that can detect itaconate in a semi-quantitative 17 manner and, when combined with the itaR gene, is sufficient for itaconate-regulated expression 18 in E. coli. Using this biosensor with fluorescence microscopy, we observe bacteria responding to 19 itaconate in the phagosomes of macrophage and provide additional evidence that interferon-γ 20 stimulates macrophage itaconate synthesis and that mouse macrophage produce substantially 21 more itaconate than human cells. In summary, we examine the role of itaconate as an 22 antibacterial metabolite in mouse and human macrophage, characterize the regulation of 23 Salmonella's defense against it, and develop it as a convenient itaconate biosensor and 24 inducible promoter system. 25 26 Importance 27In response to invading bacteria, immune cells can produce a molecule called itaconate, 28 which can inhibit microbial metabolism. Here we show that itaconate can also directly kill 29 3 Salmonella when combined with moderate acidity, further supporting itaconate's role as an 30 antibacterial weapon. We also discover how Salmonella recognizes itaconate and activates a 31 defense to degrade it, and we harness this response to make a biosensor that detects the 32 presence of itaconate. This biosensor is versatile, working in Salmonella or harmless E. coli, and 33 can detect itaconate quantitatively in the environment and in immune cells. By understanding 34 how immune cells kill bacteria and how the microbes defend themselves, we can better 35 develop novel antibiotics to inhibit pathogens such as Salmonella. 36 37 42 Salmonella pathogenicity islands (SPI) that support its survival inside of a host organism. For 43 instance, Salmonella employs SPI-1 to invade non-phagocytic cells, and SPI-2 allows the bacteria 44 to survive intracellularly -including in macrophage -which is important for Salmonella 45 virulence (1-4). These traits allow Salmonella to invade the gut epithelium and induce intestinal 46 inflammation resulting in the characteristic gastroenteritis disease. Moreover, the induced 47 65 catalyzing the degradation of itaconate into pyruvate and acetyl-CoA (16). This operon is not 66 restricted to Yersinia and a variety of other pathogens encode homologs. These...

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Section: Discussionsupporting

confidence: 55%

Section: Introductionmentioning

confidence: 99%

The Salmonella LysR family regulator, RipR, activates the SPI-13 encoded itaconate degradation cluster

Hersch

Navarre

2019

Preprint

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“…Fluorescent Salmonella Enteritidis enables SPI-1 quantitation in the intestines of chicks. Having determined that our fluorescent proteins did not interfere with virulence, we moved these constructs into S. Enteritidis strain CDC_2010K_0968, a clinical isolate associated with the 2010 egg outbreak of Salmonella infection in the United States (28,29). The strain behaved as expected in vitro (see Fig.…”

Section: Resultsmentioning

confidence: 91%

“…An isogenic ΔphoN::kan mutant was also constructed and used as the wild-type strain in mouse competition. Salmonella Enteritidis strain MD15 (a gift from Devendra Shah [28,29]) was the background for all strain variants employed in chicken studies. To generate a nalidixic acid-resistant isolate, 100 l of a log-phase culture was plated on LB agar containing 100 g/ml nalidixic acid.…”

Section: Methodsmentioning

confidence: 99%

Salmonella Pathogenicity Island 1 Is Expressed in the Chicken Intestine and Promotes Bacterial Proliferation

et al. 2019

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Salmonella enterica serovar Enteritidis is a common cause of foodborne illness in the United States. The bacterium can be transmitted to humans via contaminated chicken meat and eggs, and virulence in humans requires type III secretion system 1 (TTSS-1), encoded on Salmonella pathogenicity island 1 (SPI-1). Chickens often carry S. Enteritidis subclinically, obscuring the role of SPI-1 in facilitating bacterial colonization. To evaluate the role of SPI-1 in the infection of chicks by Salmonella, we created and utilized strains harboring a stable fluorescent reporter fusion designed to quantify SPI-1 expression within the intestinal tracts of animals. Using mutants unable to express TTSS-1, we demonstrated the important role of the secretion system in facilitating bacterial colonization. We further showed that coinoculation of an SPI-1 mutant with the wild-type strain increased the number of mutant organisms in intestinal tissue and contents, suggesting that the wild type rescues the mutant. Our results support the hypothesis that SPI-1 facilitates S. Enteritidis colonization of the chicken and make SPI-1 an attractive target in preventing Salmonella carriage and colonization in chickens to reduce contamination of poultry meat and eggs by this foodborne pathogen.

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“…SPI-2 to SPI-4 are necessary for bacterial survival and proliferation inside host cells, and SPI-5 seems to be involved in inflammation and chloride secretion [32]. SPI-13 and SPI-14 are known to be able to promote colonization of Salmonella in the host intestine [33,34]. The presence of SPIs in ST1120 was explored by using the newly developed Web tool SPIFinder 1.0.…”

Section: Pathogenesis and Virulence Factorsmentioning

confidence: 99%

Genomic Approaches for Understanding the Characteristics of Salmonella enterica subsp. enterica Serovar Typhimurium ST1120, Isolated from Swine Feces in Korea

Kim¹,

Kim²,

Park³

et al. 2017

Journal of Microbiology and Biotechnology

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subsp. serovar Typhimurium, one of the most common foodborne pathogens, is transmitted mainly through contaminated food derived from infected animals. In this study, Typhimurium ST1120, an isolate from pig feces in Korea, was subjected to whole-genome analysis to understand its genomic features associated with virulence. The genome of ST1120 was found to have a circular chromosome of 4,855,001 bp (GC content 52.2%) and a plasmid of 6,863 bp (GC content 46.0%). This chromosome was predicted to have 4,558 open reading frames (ORFs), 17 pseudogenes, 22 rRNA genes, and 86 tRNA genes. Its plasmid was predicted to have three ORFs. Comparative genome analysis revealed that ST1120 was phylogenetically close to Typhimurium U288, a critical isolate in piggery farms and food chains in Europe. In silico functional analysis predicted that the ST1120 genome harbored multiple genes associated with virulence and stress resistance, including pathogenicity islands (SPIs containing SPI-1 to SPI-5, SPI-13, and SPI-14), C63PI locus, ST104 prophage locus, and various antibiotic resistance genes. In accordance with these analysis results, ST1120 showed competence in invasion and survival abilities when it was added to host cells. It also exhibited robust resistance against antibiotics in comparison with other Typhimurium strains. This is the first report of the complete genome sequence of Typhimurium isolated from swine in Korea. Comparative genome analysis between ST1120 and other Salmonella strains would provide fruitful information toward understanding host specificity and developing control measures against Typhimurium infection.

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The Salmonella pathogenicity island 13 contributes to pathogenesis in streptomycin pre-treated mice but not in day-old chickens

Cited by 32 publications

References 34 publications

The Salmonella LysR family regulator, RipR, activates the SPI-13 encoded itaconate degradation cluster

The Salmonella LysR family regulator, RipR, activates the SPI-13 encoded itaconate degradation cluster

Salmonella Pathogenicity Island 1 Is Expressed in the Chicken Intestine and Promotes Bacterial Proliferation

Genomic Approaches for Understanding the Characteristics of Salmonella enterica subsp. enterica Serovar Typhimurium ST1120, Isolated from Swine Feces in Korea

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