Original Article Perspectives on Super-Shedding of Escherichia coli O157:H7 by Cattle Krysty D. Munns, 1,2 L. Brent Selinger, 1 Kim Stanford, 3 Leluo Guan, 4 Todd R. Callaway, 5 and Tim A. McAllister 1 Abstract Escherichia coli O157:H7 is a foodborne pathogen that causes illness in humans worldwide. Cattle are the primary reservoir of this bacterium, with the concentration and frequency of E. coli O157:H7 shedding varying greatly among individuals. The term ‘‘super-shedder’’ has been applied to cattle that shed concentrations of E. coli O157:H7 ‡ 10 4 colony-forming units/g feces. Super-shedders have been reported to have a substantial impact on the prevalence and transmission of E. coli O157:H7 in the environment. The specific factors responsible for super-shedding are unknown, but are presumably mediated by characteristics of the bacterium, animal host, and environment. Super-shedding is sporadic and inconsistent, suggesting that biofilms of E. coli O157:H7 colonizing the intestinal epithelium in cattle are intermittently released into feces. Phenotypic and genotypic differences have been noted in E. coli O157:H7 recovered from super-shedders as compared to low-shedding cattle, including differences in phage type (PT21/28), carbon utilization, degree of clonal relatedness, tir poly- morphisms, and differences in the presence of stx2a and stx2c, as well as antiterminator Q gene alleles. There is also some evidence to support that the native fecal microbiome is distinct between super-shedders and low- shedders and that low-shedders have higher levels of lytic phage within feces. Consequently, conditions within the host may determine whether E. coli O157:H7 can proliferate sufficiently for the host to obtain super-shedding status. Targeting super-shedders for mitigation of E. coli O157:H7 has been proposed as a means of reducing the incidence and spread of this pathogen to the environment. If super-shedders could be easily identified, strategies such as bacteriophage therapy, probiotics, vaccination, or dietary inclusion of plant secondary compounds could be specifically targeted at this subpopulation. Evidence that super-shedder isolates share a commonality with isolates linked to human illness makes it imperative that the etiology of this phenomenon be characterized. Escherichia coli O157:H7 E scherichia coli O157:H7 is a Shiga-toxin–producing, non-sorbitol-fermenting human pathogen that asymp- tomatically colonizes cattle as a primary reservoir (Wells et al., 1991; Chapman et al., 1993; Ferens and Hovde, 2011). Transmission to humans can occur through the consumption of contaminated food or water, person-to-person contact, or direct contact with animal feces or an animal reservoir (Fe- rens and Hovde, 2011). Infection in humans may remain asymptomatic or result in gastroenteritis including bloody diarrhea (hemorrhagic colitis), which can progress to renal failure through hemolytic uremic syndrome, resulting in mortalities, especially in children. Research suggests that consumption of as few as 10 cells of E. coli O157:H7 can cause human infections (Schmid-Hempel and Frank, 2007), but individual strains differ in virulence (Baker et al., 2007). The pathogenicity of E. coli O157:H7 is attributed, in part, to the production of verotoxins or Shiga-like toxins named so because of their similarity to the toxins produced by Shigella dysenteriae (O’Brien et al., 1992). Lysogenic bacteriophages carry the genes responsible for producing these toxins (stx1 and stx2) that inhibit protein synthesis in eukaryotic cells (Rashid et al., 2006) by decreasing the activity of ribosomal RNA, leading to cell death (Endo et al., 1988). In the United States, E. coli O157:H7 infections cause over 73,000 ill- nesses and 61 deaths per year ( Mead et al., 1999), costing the American healthcare system approximately $405 million 1 Agriculture and Agri-Food Canada, Lethbridge Research Centre, Lethbridge, Alberta, Canada. 2 Department of Biological Sciences, University of Lethbridge, Lethbridge, Alberta, Canada. 3 Alberta Agriculture and Rural Development, Lethbridge, Alberta, Canada. 4 Department of Agriculture, Food, and Nutritional Science, University of Alberta, Edmonton, Alberta, Canada. 5 Food and Feed Safety Research Unit, U.S. Department of Agriculture/Agricultural Research Service, College Station, Texas. FOODBORNE PATHOGENS AND DISEASE Volume 12, Number 2, 2015 ª Mary Ann Liebert, Inc. DOI: 10.1089/fpd.2014.1829 1