Differences in host cell invasion and Salmonella pathogenicity island 1 expression between Salmonella enterica serovar Paratyphi A and nontyphoidal S. Typhimurium

Dana Elhadad, Prerak Desai, Guntram A. Grassl, Michael McClelland, Galia Rahav, Ohad Gal-Mor*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

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 serovar S. Paratyphi A compared to that of the nontyphoidal serovar S. 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 in S. Paratyphi A. Using streptomycin-treated mice, we were able to establish substantial intestinal colonization by S. 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 and S. 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.

Original languageEnglish
Pages (from-to)1150-1165
Number of pages16
JournalInfection and Immunity
Volume84
Issue number4
DOIs
StatePublished - 1 Apr 2016

Funding

FundersFunder number
Foundation for Scientific Research and Development
Israel Institute of Technology, Haifa, Israel
Lea Valinsky
Michael McClelland
Ministry of Health Central Laboratories
National Institutes of HealthAI077645, AI039557, AI083646, HHSN272200900040C, AI052237, AI075093
Foundation for the National Institutes of Health
National Institute of Allergy and Infectious DiseasesR01AI073971
U.S. Department of Agriculture2009-03579, 2011-67017-30127
United States - Israel Binational Agricultural Research and Development Fund
Center for Produce Safety
Deutsches Zentrum für Infektionsforschung
Deutsche ForschungsgemeinschaftGR2666/5-1
German-Israeli Foundation for Scientific Research and Development1096-39.11/2010
Israel Science Foundation999/14
Technion-Israel Institute of Technology

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