title: Characterization of the Invasive, Multidrug Resistant Non-typhoidal Salmonella Strain D23580 in a Murine Model of Infection.
abstract: A distinct pathovar of Salmonella enterica serovar Typhimurium, ST313, has emerged in sub-Saharan Africa as a major cause of fatal bacteremia in young children and HIV-infected adults. D23580, a multidrug resistant clinical isolate of ST313, was previously shown to have undergone genome reduction in a manner that resembles that of the more human-restricted pathogen, Salmonella enterica serovar Typhi. It has since been shown through tissue distribution studies that D23580 is able to establish an invasive infection in chickens. However, it remains unclear whether ST313 can cause lethal disease in a non-human host following a natural course of infection. Herein we report that D23580 causes lethal and invasive disease in a murine model of infection following peroral challenge. The LD50 of D23580 in female BALB/c mice was 4.7 x 10(5) CFU. Tissue distribution studies performed 3 and 5 days post-infection confirmed that D23580 was able to more rapidly colonize the spleen, mesenteric lymph nodes and gall bladder in mice when compared to the well-characterized S. Typhimurium strain SL1344. D23580 exhibited enhanced resistance to acid stress relative to SL1344, which may lend towards increased capability to survive passage through the gastrointestinal tract as well as during its intracellular lifecycle. Interestingly, D23580 also displayed higher swimming motility relative to SL1344, S. Typhi strain Ty2, and the ST313 strain A130. Biochemical tests revealed that D23580 shares many similar metabolic features with SL1344, with several notable differences in the Voges-Proskauer and catalase tests, as well alterations in melibiose, and inositol utilization. These results represent the first full duration infection study using an ST313 strain following the entire natural course of disease progression, and serve as a benchmark for ongoing and future studies into the pathogenesis of D23580.
authors.affiliation: Center for Infectious Diseases and Vaccinology, The Biodesign Institute, Arizona State University, Tempe, Arizona, United States of America.
authors.forename: Jiseon
authors.initials: J
authors.lastname: Yang
authors.affiliation: Center for Infectious Diseases and Vaccinology, The Biodesign Institute, Arizona State University, Tempe, Arizona, United States of America.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Barrila
authors.affiliation: Center for Infectious Diseases and Vaccinology, The Biodesign Institute, Arizona State University, Tempe, Arizona, United States of America.
authors.forename: Kenneth L
authors.initials: KL
authors.lastname: Roland
authors.affiliation: Center for Infectious Diseases and Vaccinology, The Biodesign Institute, Arizona State University, Tempe, Arizona, United States of America.
authors.forename: Jacquelyn
authors.initials: J
authors.lastname: Kilbourne
authors.affiliation: Biomedical Research and Environmental Sciences Division, NASA Johnson Space Center, Houston, Texas, United States of America.
authors.forename: C Mark
authors.initials: CM
authors.lastname: Ott
authors.affiliation: Center for Infectious Diseases and Vaccinology, The Biodesign Institute, Arizona State University, Tempe, Arizona, United States of America.
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Forsyth
authors.affiliation: Center for Infectious Diseases and Vaccinology, The Biodesign Institute, Arizona State University, Tempe, Arizona, United States of America; School of Life Sciences, Arizona State University, Tempe, Arizona, United States of America.
authors.forename: Cheryl A
authors.initials: CA
authors.lastname: Nickerson
mesh_terms: D000818:Animals; D024901:Drug Resistance, Multiple, Bacterial; D005260:Female; D005704:Gallbladder / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D012475:Salmonella / Q000145:classification* / Q000187:drug effects*; D012481:Salmonella Infections, Animal / Q000382:microbiology*; D013154:Spleen / Q000382:microbiology