Salmonella enterica serovar-specific transcriptional reprogramming of infected cells

Hannemann, Sebastian; Galán, Jorge E.

doi:10.1371/journal.ppat.1006532

Cited by 29 publications

(31 citation statements)

References 50 publications

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“…4c). A previous report indicated that S. Typhimurium infection results in STAT3 phosphorylation in HeLa and Henle epithelial cells but did not identify the causative effector (Hannemann and Galan, 2017). We confirmed S .…”

Section: Resultsmentioning

confidence: 99%

Salmonella Activation of STAT3 Signaling by SarA Effector Promotes Intracellular Replication and Production of IL-10

et al. 2018

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Salmonella enterica is an important foodborne pathogen that uses secreted effector proteins to manipulate host pathways to facilitate survival and dissemination. Different S. enterica serovars cause disease syndromes ranging from gastroenteritis to typhoid fever and vary in their effector repertoire. We leveraged this natural diversity to identify stm2585, here designated sarA (Salmonella anti-inflammatory response activator), as a Salmonella effector that induces production of the anti-inflammatory cytokine IL-10. RNA-seq of cells infected with either ΔsarA or wild-type S. Typhimurium revealed that SarA activates STAT3 transcriptional targets. Consistent with this, SarA is necessary and sufficient for STAT3 phosphorylation, STAT3 inhibition blocks IL-10 production, and SarA and STAT3 interact by co-immunoprecipitation. These effects of SarA contribute to intracellular replication in vitro and bacterial load at systemic sites in mice. Our results demonstrate the power of using comparative genomics for identifying effectors and that Salmonella has evolved mechanisms for activating an important anti-inflammatory pathway.

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Section: Resultsmentioning

confidence: 99%

Salmonella Activation of STAT3 Signaling by SarA Effector Promotes Intracellular Replication and Production of IL-10

et al. 2018

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“…Importantly, although there is a bias towards discussing the pseudogenisation and absence of T3SS effectors in S. Typhi, computational or experimental screens to identify novel effectors have, to our knowledge, not been performed with S. Typhi. However, based on homology to T3SS effectors from other bacterial pathogens, putative S. Typhi-specific effectors have been identified, including STY1076 (NleG family), STY1423 (EspN), and STY1360 (OspB) (Hannemann & Galán, 2017). Of these, STY1076 (t1865) can be secreted in a SPI-1 and SPI-2 T3SS-dependent manner, and translocated into host cells, although a functional role during S. Typhi infection has not yet been described (manuscript in preparation).…”

Section: Gogamentioning

confidence: 99%

“…However, based on homology to T3SS effectors from other bacterial pathogens, putative S. Typhi-specific effectors have been identified, including STY1076 (NleG family), STY1423 (EspN), and STY1360 (OspB)(Hannemann & Galán, 2017). These results suggest that SptP is nonfunctional in S. Typhi, which may have wider ramifications when considering additional effectors with varying sequence identities between S. Typhi and S. Typhimurium.…”

mentioning

confidence: 99%

TyphoidalSalmonella: Distinctive virulence factors and pathogenesis

Johnson

Mylona

Frankel

2018

Cellular Microbiology

141

106

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Although nontyphoidal Salmonella (NTS; including Salmonella Typhimurium) mainly cause gastroenteritis, typhoidal serovars (Salmonella Typhi and Salmonella Paratyphi A) cause typhoid fever, the treatment of which is threatened by increasing drug resistance. Our understanding of S. Typhi infection in human remains poorly understood, likely due to the host restriction of typhoidal strains and the subsequent popularity of the S. Typhimurium mouse typhoid model. However, translating findings with S. Typhimurium across to S. Typhi has some limitations. Notably, S. Typhi has specific virulence factors, including typhoid toxin and Vi antigen, involved in symptom development and immune evasion, respectively. In addition to unique virulence factors, both typhoidal and NTS rely on two pathogenicity-island encoded type III secretion systems (T3SS), the SPI-1 and SPI-2 T3SS, for invasion and intracellular replication. Marked differences have been observed in terms of T3SS regulation in response to bile, oxygen, and fever-like temperatures. Moreover, approximately half of effectors found in S. Typhimurium are either absent or pseudogenes in S. Typhi, with most of the remaining exhibiting sequence variation. Typhoidal-specific T3SS effectors have also been described. This review discusses what is known about the pathogenesis of typhoidal Salmonella with emphasis on unique behaviours and key differences when compared with S. Typhimurium.

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“…S. Typhimurium can directly benefit from hyperaccuracy of translation through accurate protein production and proteome integrity and indirectly through proper activation of the stringent response during adverse growth conditions. S. Typhimurium can use these translational stress responses to complement the well-characterized transcriptional responses that are the foundation for S. Typhimurium pathogenesis to maintain resiliency during oxidative stress and survive within the host microbiome (30)(31)(32).…”

Section: Proofreading Protects Cells From Mistranslation Under Adversementioning

confidence: 99%

Oxidation of phenylalanyl-tRNA synthetase positively regulates translational quality control

Steiner

Kyle

Ibba

2019

Proc. Natl. Acad. Sci. U.S.A.

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Accurate translation of the genetic code is maintained in part by aminoacyl-tRNA synthetases (aaRS) proofreading mechanisms that ensure correct attachment of a cognate amino acid to a transfer RNA (tRNA). During environmental stress, such as oxidative stress, demands on aaRS proofreading are altered by changes in the availability of cytoplasmic amino acids. For example, oxidative stress increases levels of cytotoxic tyrosine isomers, noncognate amino acids normally excluded from translation by the proofreading activity of phenylalanyl-tRNA synthetase (PheRS). Here we show that oxidation of PheRS induces a conformational change, generating a partially unstructured protein. This conformational change does not affect Phe or Tyr activation or the aminoacylation activity of PheRS. However, in vitro and ex vivo analyses reveal that proofreading activity to hydrolyze Tyr-tRNA Phe is increased during oxidative stress, while the cognate Phe-tRNA Phe aminoacylation activity is unchanged. In HPX − , Escherichia coli that lack reactive oxygen-scavenging enzymes and accumulate intracellular H 2 O 2 , we found that PheRS proofreading is increased by 11%, thereby providing potential protection against hazardous cytoplasmic m-Tyr accumulation. These findings show that in response to oxidative stress, PheRS proofreading is positively regulated without negative effects on the enzyme's housekeeping activity in translation. Our findings also illustrate that while the loss of quality control and mistranslation may be beneficial under some conditions, increased proofreading provides a mechanism for the cell to appropriately respond to environmental changes during oxidative stress.aminoacyl-tRNA | oxidative stress | proofreading | quality control

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Salmonella enterica serovar-specific transcriptional reprogramming of infected cells

Cited by 29 publications

References 50 publications

Salmonella Activation of STAT3 Signaling by SarA Effector Promotes Intracellular Replication and Production of IL-10

Salmonella Activation of STAT3 Signaling by SarA Effector Promotes Intracellular Replication and Production of IL-10

TyphoidalSalmonella: Distinctive virulence factors and pathogenesis

Oxidation of phenylalanyl-tRNA synthetase positively regulates translational quality control

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