| Abstract: | BackgroundS. Typhi, a human-restricted Salmonellaenterica serovar, causes a systemic intracellular infection inhumans (typhoid fever). In comparison, S. Typhimuriumcauses gastroenteritis in humans, but causes a systemic typhoidal illness inmice. The PhoP regulon is a well studied two component (PhoP/Q) coordinatelyregulated network of genes whose expression is required for intracellularsurvival of S. enterica.Methodology/Principal FindingsUsing high performance liquid chromatography mass spectrometry (HPLC-MS/MS),we examined the protein expression profiles of three sequenced S.enterica strains: S. Typhimurium LT2,S. Typhi CT18, and S. Typhi Ty2 inPhoP-inducing and non-inducing conditions in vitro andcompared these results to profiles ofphoP−/Q−mutants derived from S. Typhimurium LT2 andS. Typhi Ty2. Our analysis identified 53 proteins inS. Typhimurium LT2 and 56 proteins inS. Typhi that were regulated in a PhoP-dependent manner. Asexpected, many proteins identified in S. Typhi demonstratedconcordant differential expression with a homologous protein inS. Typhimurium. However, three proteins (HlyE, STY1499, andCdtB) had no homolog in S. Typhimurium. HlyE is apore-forming toxin. STY1499 encodes a stably expressed protein of unknownfunction transcribed in the same operon as HlyE. CdtB is a cytolethaldistending toxin associated with DNA damage, cell cycle arrest, and cellulardistension. Gene expression studies confirmed up-regulation of mRNA of HlyE,STY1499, and CdtB in S. Typhi in PhoP-inducingconditions.Conclusions/SignificanceThis study is the first protein expression study of the PhoP virulenceassociated regulon using strains of Salmonella mutant inPhoP, has identified three Typhi-unique proteins (CdtB, HlyE and STY1499)that are not present in the genome of the wide host-range Typhimurium, andincludes the first protein expression profiling of a live attenuatedbacterial vaccine studied in humans (Ty800). |
