Intraspecies variation in the emergence of hyperinfectious bacterial strains in nature

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. © 2012 mahan et al.