PLoS Pathogens | |
Intraspecies Variation in the Emergence of Hyperinfectious Bacterial Strains in Nature | |
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
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