Intraspecies variation in the emergence of hyperinfectious bacterial strains in nature

Douglas M. Heithoff, William R. Shimp, John K. House, Yi Xie, Bart C Weimer, Robert L. Sinsheimer, Michael J. Mahan

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

Salmonella is a principal health concern because of its endemic prevalence in food and water supplies, the rise in incidence of multi-drug resistant strains, and the emergence of new strains associated with increased disease severity. Insights into pathogen emergence have come from animal-passage studies wherein virulence is often increased during infection. However, these studies did not address the prospect that a select subset of strains undergo a pronounced increase in virulence during the infective process- a prospect that has significant implications for human and animal health. Our findings indicate that the capacity to become hypervirulent (100-fold decreased LD50) was much more evident in certain S. enterica strains than others. Hyperinfectious salmonellae were among the most virulent of this species; restricted to certain serotypes; and more capable of killing vaccinated animals. Such strains exhibited rapid (and rapidly reversible) switching to a less-virulent state accompanied by more competitive growth ex vivo that may contribute to maintenance in nature. The hypervirulent phenotype was associated with increased microbial pathogenicity (colonization; cytotoxin production; cytocidal activity), coupled with an altered innate immune cytokine response within infected cells (IFN-β; IL-1β; IL-6; IL-10). Gene expression analysis revealed that hyperinfectious strains display altered transcription of genes within the PhoP/PhoQ, PhoR/PhoB and ArgR regulons, conferring changes in the expression of classical virulence functions (e.g., SPI-1; SPI-2 effectors) and those involved in cellular physiology/metabolism (nutrient/acid stress). As hyperinfectious strains pose a potential risk to human and animal health, efforts toward mitigation of these potential food-borne contaminants may avert negative public health impacts and industry-associated losses.

Original languageEnglish (US)
Article numbere1002647
JournalPLoS Pathogens
Volume8
Issue number4
DOIs
StatePublished - Apr 2012

Fingerprint

Virulence
Salmonella
Health
Food
Regulon
Food Supply
Water Supply
Lethal Dose 50
Cytotoxins
Interleukin-1
Innate Immunity
Interleukin-10
Interleukin-6
Industry
Public Health
Maintenance
Cytokines
Phenotype
Gene Expression
Acids

ASJC Scopus subject areas

  • Microbiology
  • Parasitology
  • Virology
  • Immunology
  • Genetics
  • Molecular Biology

Cite this

Heithoff, D. M., Shimp, W. R., House, J. K., Xie, Y., Weimer, B. C., Sinsheimer, R. L., & Mahan, M. J. (2012). Intraspecies variation in the emergence of hyperinfectious bacterial strains in nature. PLoS Pathogens, 8(4), [e1002647]. https://doi.org/10.1371/journal.ppat.1002647

Intraspecies variation in the emergence of hyperinfectious bacterial strains in nature. / Heithoff, Douglas M.; Shimp, William R.; House, John K.; Xie, Yi; Weimer, Bart C; Sinsheimer, Robert L.; Mahan, Michael J.

In: PLoS Pathogens, Vol. 8, No. 4, e1002647, 04.2012.

Research output: Contribution to journalArticle

Heithoff, DM, Shimp, WR, House, JK, Xie, Y, Weimer, BC, Sinsheimer, RL & Mahan, MJ 2012, 'Intraspecies variation in the emergence of hyperinfectious bacterial strains in nature', PLoS Pathogens, vol. 8, no. 4, e1002647. https://doi.org/10.1371/journal.ppat.1002647
Heithoff, Douglas M. ; Shimp, William R. ; House, John K. ; Xie, Yi ; Weimer, Bart C ; Sinsheimer, Robert L. ; Mahan, Michael J. / Intraspecies variation in the emergence of hyperinfectious bacterial strains in nature. In: PLoS Pathogens. 2012 ; Vol. 8, No. 4.
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