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PhoP-Mediated Repression of the SPI1 Type 3 Secretion System in Salmonella enterica Serovar Typhimurium.
J Bacteriol. 2019 08 15; 201(16)JB

Abstract

Salmonella must rapidly adapt to various niches in the host during infection. Relevant virulence factors must be appropriately induced, and systems that are detrimental in a particular environment must be turned off. Salmonella infects intestinal epithelial cells using a type 3 secretion system (T3SS) encoded on Salmonella pathogenicity island 1 (SPI1). The system is controlled by three AraC-like regulators, HilD, HilC, and RtsA, which form a complex feed-forward loop to activate expression of hilA, encoding the main transcriptional regulator of T3SS structural genes. This system is tightly regulated, with many of the activating signals acting at the level of hilD translation or HilD protein activity. Once inside the phagosomes of epithelial cells, or in macrophages during systemic stages of disease, the SPI1 T3SS is no longer required or expressed. Here, we show that the PhoPQ two-component system, critical for intracellular survival, appears to be the primary mechanism by which Salmonella shuts down the SPI1 T3SS. PhoP negatively regulates hilA through multiple distinct mechanisms: direct transcriptional repression of the hilA promoter, indirect transcriptional repression of both the hilD and rtsA promoters, and activation of the small RNA (sRNA) PinT. Genetic analyses and electrophoretic mobility shift assays suggest that PhoP specifically binds the hilA promoter to block binding of activators HilD, HilC, and RtsA as a mechanism of repression.IMPORTANCESalmonella is one of the most common foodborne pathogens, causing an estimated 1.2 million illnesses per year in the United States. A key step in infection is the activation of the bacterial invasion machinery, which induces uptake of the bacterium into epithelial cells and leads to induction of inflammatory diarrhea. Upon entering the vacuolar compartments of host cells, Salmonella senses an environmental transition and represses the invasion machinery with a two-component system relevant for survival within the vacuole. This adaptation to specific host niches is an important example of how signals are integrated for survival of the pathogen.

Authors+Show Affiliations

Department of Microbiology, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.Department of Microbiology, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.Department of Microbiology, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA slauch@illinois.edu.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

31182495

Citation

Palmer, Alexander D., et al. "PhoP-Mediated Repression of the SPI1 Type 3 Secretion System in Salmonella Enterica Serovar Typhimurium." Journal of Bacteriology, vol. 201, no. 16, 2019.
Palmer AD, Kim K, Slauch JM. PhoP-Mediated Repression of the SPI1 Type 3 Secretion System in Salmonella enterica Serovar Typhimurium. J Bacteriol. 2019;201(16).
Palmer, A. D., Kim, K., & Slauch, J. M. (2019). PhoP-Mediated Repression of the SPI1 Type 3 Secretion System in Salmonella enterica Serovar Typhimurium. Journal of Bacteriology, 201(16). https://doi.org/10.1128/JB.00264-19
Palmer AD, Kim K, Slauch JM. PhoP-Mediated Repression of the SPI1 Type 3 Secretion System in Salmonella Enterica Serovar Typhimurium. J Bacteriol. 2019 08 15;201(16) PubMed PMID: 31182495.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - PhoP-Mediated Repression of the SPI1 Type 3 Secretion System in Salmonella enterica Serovar Typhimurium. AU - Palmer,Alexander D, AU - Kim,Kyungsub, AU - Slauch,James M, Y1 - 2019/07/24/ PY - 2019/04/12/received PY - 2019/05/31/accepted PY - 2019/6/12/pubmed PY - 2020/6/5/medline PY - 2019/6/12/entrez KW - PhoPQ KW - Salmonella KW - virulence regulation JF - Journal of bacteriology JO - J Bacteriol VL - 201 IS - 16 N2 - Salmonella must rapidly adapt to various niches in the host during infection. Relevant virulence factors must be appropriately induced, and systems that are detrimental in a particular environment must be turned off. Salmonella infects intestinal epithelial cells using a type 3 secretion system (T3SS) encoded on Salmonella pathogenicity island 1 (SPI1). The system is controlled by three AraC-like regulators, HilD, HilC, and RtsA, which form a complex feed-forward loop to activate expression of hilA, encoding the main transcriptional regulator of T3SS structural genes. This system is tightly regulated, with many of the activating signals acting at the level of hilD translation or HilD protein activity. Once inside the phagosomes of epithelial cells, or in macrophages during systemic stages of disease, the SPI1 T3SS is no longer required or expressed. Here, we show that the PhoPQ two-component system, critical for intracellular survival, appears to be the primary mechanism by which Salmonella shuts down the SPI1 T3SS. PhoP negatively regulates hilA through multiple distinct mechanisms: direct transcriptional repression of the hilA promoter, indirect transcriptional repression of both the hilD and rtsA promoters, and activation of the small RNA (sRNA) PinT. Genetic analyses and electrophoretic mobility shift assays suggest that PhoP specifically binds the hilA promoter to block binding of activators HilD, HilC, and RtsA as a mechanism of repression.IMPORTANCESalmonella is one of the most common foodborne pathogens, causing an estimated 1.2 million illnesses per year in the United States. A key step in infection is the activation of the bacterial invasion machinery, which induces uptake of the bacterium into epithelial cells and leads to induction of inflammatory diarrhea. Upon entering the vacuolar compartments of host cells, Salmonella senses an environmental transition and represses the invasion machinery with a two-component system relevant for survival within the vacuole. This adaptation to specific host niches is an important example of how signals are integrated for survival of the pathogen. SN - 1098-5530 UR - https://www.unboundmedicine.com/medline/citation/31182495/PhoP_Mediated_Repression_of_the_SPI1_Type_3_Secretion_System_in_Salmonella_enterica_Serovar_Typhimurium_ DB - PRIME DP - Unbound Medicine ER -