title: Molecular and cellular characterization of a Salmonella enterica serovar Paratyphi a outbreak strain and the human immune response to infection.
abstract: Enteric fever is an invasive life-threatening systemic disease caused by the Salmonella enterica human-adapted serovars Typhi and Paratyphi. Increasing incidence of infections with Salmonella enterica serovar Paratyphi A and the spreading of its antibiotic-resistant derivates pose a significant health concern in some areas of the world. Herein, we describe a molecular and phenotypic characterization of an S. Paratyphi A strain accounted for a recent paratyphoid outbreak in Nepal that affected at least 37 travelers. Pulsed-field gel electrophoresis analysis of the outbreak isolates revealed one genetic clone (pulsotype), confirming a single infecting source. Genetic profiling of the outbreak strain demonstrated the contribution of specific bacteriophages as a prime source of genetic diversity among clinical isolates of S. Paratyphi A. Phenotypic characterization in comparison with the S. Paratyphi A ATCC 9150 reference sequenced strain showed differences in flagellar morphology and increased abilities of the outbreak strain with respect to its motility, invasion into nonphagocytic cells, intracellular multiplication, survival within macrophages, and higher induction of interleukin-8 (IL-8) secreted by host cells. Collectively, these differences suggest an enhanced virulence potential of this strain and demonstrate an interesting phenotypic variation among S. Paratyphi A isolates. In vivo profiling of 16 inflammatory cytokines in patients infected with the outbreak strain revealed a common profile of a remarkable gamma interferon (IFN-γ) induction together with elevated concentrations of tumor necrosis factor alpha (TNF-α), IL-6, IL-8, IL-10, and IL-15, but not IL-12, which was previously demonstrated as elevated in nontyphoidal Salmonella infections. This apparent profile implies a distinct immune response to paratyphoid infections.
authors.affiliation: Infectious Diseases Research Laboratory, Sheba Medical Center, Tel-Hashomer, Israel. Ohad.Gal-Mor@sheba.health.gov.il
authors.forename: Ohad
authors.initials: O
authors.lastname: Gal-Mor
authors.forename: Jotham
authors.initials: J
authors.lastname: Suez
authors.forename: Dana
authors.initials: D
authors.lastname: Elhadad
authors.forename: Steffen
authors.initials: S
authors.lastname: Porwollik
authors.forename: Eyal
authors.initials: E
authors.lastname: Leshem
authors.forename: Lea
authors.initials: L
authors.lastname: Valinsky
authors.forename: Michael
authors.initials: M
authors.lastname: McClelland
authors.forename: Eliezer
authors.initials: E
authors.lastname: Schwartz
authors.forename: Galia
authors.initials: G
authors.lastname: Rahav
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D001435:Bacteriophages / Q000235:genetics; D018938:Caco-2 Cells; D016207:Cytokines / Q000032:analysis; D004269:DNA, Bacterial / Q000235:genetics; D024881:Drug Resistance, Bacterial; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006367:HeLa Cells; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D007557:Israel; D008264:Macrophages / Q000382:microbiology; D008297:Male; D051379:Mice; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D009390:Nepal / Q000453:epidemiology; D010284:Paratyphoid Fever / Q000453:epidemiology / Q000276:immunology* / Q000382:microbiology*; D010641:Phenotype; D012482:Salmonella paratyphi A / Q000187:drug effects / Q000235:genetics* / Q000276:immunology* / Q000302:isolation & purification; D017422:Sequence Analysis, DNA; D055815:Young Adult
chemical_list: D016207:Cytokines; D004269:DNA, Bacterial; D016209:Interleukin-8