Characterization of the invasive, multidrug resistant non-typhoidal Salmonella strain D23580 in a murine model of infection

Jiseon Yang, Jennifer Barrila, Kenneth L. Roland, Jacquelyn Kilbourne, C. Mark Ott, Rebecca J. Forsyth, Cheryl Nickerson

Research output: Contribution to journalArticle

16 Citations (Scopus)

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 humanrestricted 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 LD<inf>50</inf> of D23580 in female BALB/c mice was 4.7 x 10<sup>5</sup> 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.

Original languageEnglish (US)
Article numbere0003839
JournalPLoS Neglected Tropical Diseases
Volume9
Issue number6
DOIs
StatePublished - Jun 19 2015

Fingerprint

Salmonella
Infection
Tissue Distribution
A-130A
Melibiose
Benchmarking
Salmonella typhi
Salmonella enterica
Africa South of the Sahara
Lethal Dose 50
Inositol
Bacteremia
Catalase
Disease Progression
Gastrointestinal Tract
Chickens
Urinary Bladder
Spleen
Lymph Nodes
HIV

ASJC Scopus subject areas

  • Infectious Diseases
  • Public Health, Environmental and Occupational Health
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Characterization of the invasive, multidrug resistant non-typhoidal Salmonella strain D23580 in a murine model of infection. / Yang, Jiseon; Barrila, Jennifer; Roland, Kenneth L.; Kilbourne, Jacquelyn; Ott, C. Mark; Forsyth, Rebecca J.; Nickerson, Cheryl.

In: PLoS Neglected Tropical Diseases, Vol. 9, No. 6, e0003839, 19.06.2015.

Research output: Contribution to journalArticle

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