Intraspecies Variation in the Emergence of Hyperinfectious Bacterial Strains in Nature

PLoS Pathogens

Michael J. Mahan¹  Robert L. Sinsheimer¹  Douglas M. Heithoff¹  William R. Shimp¹  Yi Xie²  Bart C. Weimer²  John K. House³ 

[1] Department of Molecular, Cellular and Developmental Biology, University of California, Santa Barbara, California, United States of America;Department of Population Health and Reproduction, School of Veterinary Medicine, University of California, Davis, California, United States of America;University of Sydney, Faculty of Veterinary Science, Camden, New South Wales, Australia

关键词: Salmonella typhimurium;    Salmonellosis;    Salmonella;    Macrophages;    Gene expression;    Cytokines;    Livestock;    Immune response;   

DOI  :  10.1371/journal.ppat.1002647

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY