title: Differences in Host Cell Invasion and Salmonella Pathogenicity Island 1 Expression between Salmonella enterica Serovar Paratyphi A and Nontyphoidal S. Typhimurium.
abstract: Active invasion into nonphagocytic host cells is central to Salmonella enterica pathogenicity and dependent on multiple genes within Salmonella pathogenicity island 1 (SPI-1). Here, we explored the invasion phenotype and the expression of SPI-1 in the typhoidal serovarS Paratyphi A compared to that of the nontyphoidal serovarS Typhimurium. We demonstrate that while S. Typhimurium is equally invasive under both aerobic and microaerobic conditions, S. Paratyphi A invades only following growth under microaerobic conditions. Transcriptome sequencing (RNA-Seq), reverse transcription-PCR (RT-PCR), Western blot, and secretome analyses established that S. Paratyphi A expresses much lower levels of SPI-1 genes and secretes lesser amounts of SPI-1 effector proteins than S. Typhimurium, especially under aerobic growth. Bypassing the native SPI-1 regulation by inducible expression of the SPI-1 activator, HilA, considerably elevated SPI-1 gene expression, host cell invasion, disruption of epithelial integrity, and induction of proinflammatory cytokine secretion by S. Paratyphi A but not by S. Typhimurium, suggesting that SPI-1 expression is naturally downregulated inS Paratyphi A. Using streptomycin-treated mice, we were able to establish substantial intestinal colonization byS Paratyphi A and showed moderately higher pathology and intestinal inflammation in mice infected with S. Paratyphi A overexpressing hilA Collectively, our results reveal unexpected differences in SPI-1 expression between S. Paratyphi A andS Typhimurium, indicate that S. Paratyphi A host cell invasion is suppressed under aerobic conditions, and suggest that lower invasion in aerobic sites and suppressed expression of immunogenic SPI-1 components contributes to the restrained inflammatory infection elicited by S. Paratyphi A.
authors: The Infectious Diseases Research Laboratory, Sheba Medical Center, Tel-Hashomer, Israel.|Department of Clinical Microbiology and Immunology, Tel Aviv University, Tel Aviv, Israel.|Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors: Dana
authors: D
authors: Elhadad
authors: Department of Microbiology and Molecular Genetics, University of California, Irvine, California, USA.
authors: Prerak
authors: P
authors: Desai
authors: Institute of Medical Microbiology and Hospital Epidemiology and German Centre for Infection Research (DZIF), Hannover Medical School, Hannover, Germany.
authors: Guntram A
authors: GA
authors: Grassl
authors: Department of Microbiology and Molecular Genetics, University of California, Irvine, California, USA.
authors: Michael
authors: M
authors: McClelland
authors: The Infectious Diseases Research Laboratory, Sheba Medical Center, Tel-Hashomer, Israel.|Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors: Galia
authors: G
authors: Rahav
authors: The Infectious Diseases Research Laboratory, Sheba Medical Center, Tel-Hashomer, Israel Ohad.Gal-Mor@sheba.health.gov.il.|Department of Clinical Microbiology and Immunology, Tel Aviv University, Tel Aviv, Israel.|Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors: Ohad
authors: O
authors: Gal-Mor
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D003001:Cloning, Molecular; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005260:Female; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D012482:Salmonella paratyphi A / Q000235:genetics / Q000378:metabolism*; D012486:Salmonella typhimurium / Q000235:genetics / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D016207:Cytokines; C102236:HilA protein, Salmonella; C419942:Spi1 protein, Salmonella; D015534:Trans-Activators