Persistence of Shiga Toxin-Producing Escherichia Coli (STEC) in Cattle and Association with Clinical Infections in the Same Geographic Region

Background

Human illnesses associated with Shiga toxin-producing E. coli (STEC) like E. coli O157:H7 are more prevalent in areas where there are more cattle. So there’s often an assumption that cattle harbor STEC strains that persist in the environment and are responsible for human illness. This hasn’t ever been tested, though. Cattle carry a lot of different STEC strains, but they may not all be equally likely to cause human illness. Regardless, STEC are commonly perceived as a cattle and beef issue. This perception not only undermines consumer and public confidence in our industry, it may stand in the way of effective progress towards reducing the transmission of food- or water-borne STEC outbreaks. New genomics-based technologies may allow us to more clearly determine whether a particular STEC isolated from a sick person really originated from a cattle source. 

Objectives

Compare STEC found in cattle and humans at the genetic level to understand how STEC in Alberta have evolved by: 

• Compare STEC strains isolated from cattle and humans in Alberta and Germany through comparative whole genome analysis and ancestral host reconstruction. 

• Test the association between human infections and abundant STEC strains, defined as strains isolated on cattle farms and feedlots in Alberta monthly for ≥4 months. 

• Identify and evaluate genetic signatures indicative of abundant STEC strains associated with high rates of human illness for future use in a detection assay. 

What they Did

Detailed understanding of STEC O157 strains circulating within the same geographic region in cattle and humans in Alberta is important for food safety screening and monitoring of STEC O157:H7 in both farm and clinical environments. Our study sheds light on the genetic characteristics of STEC O157 strains found in cattle and humans in Alberta. Understanding these differences is vital for improving public health measures and controlling the spread of this dangerous zoonotic pathogen. By identifying specific genetic traits, such as the phage insertion sites and antimicrobial resistance genes, researchers can develop targeted strategies to prevent and manage infections caused by STEC O157. We conducted a comparative genomic analysis of STEC O157 isolates from cattle (125 samples) and humans (127 samples) in Alberta with the goal to understand the differences in virulence genes, toxin-producing phage insertion sites, and antimicrobial resistance genes between the isolates from these two sources.

In a second study sequenced and analyzed 229 E. coli O157 isolates from cattle and humans collected between 2007 and 2015, along with three additional sets of E. coli O157:H7 isolate genomes including: 445 isolates from Alberta Health from 2009 to 2019; 152 genomes from the U.S. from 1999 to 2016; and 54 genomes from elsewhere around the world between 2007 and 2015 were used for developing a phylogenetic model to trace the origins and evolution of the bacteria and to understand persistent lineages over a longer period.

What they learned

We found that both cattle and human isolates mostly carried the same set of virulence genes: stx1, stx2, eae, and hlyA. These genes contribute to the bacteria’s ability to cause severe disease. The Shiga toxins are associated with specific sites on the bacterial genome: mlrA and wrbA. In cattle, these sites were occupied more frequently (77% for mlrA and 79% for wrbA) compared to human isolates (38% for mlrA and 1.6% for wrbA). Most of the clinical isolates (n = 95) unexpectedly had unoccupied wrbA sites and harboured sequence polymorphism. These differences suggest a significant genetic distinction between the strains found in cattle and those found in humans. The study found that about 8.8% of cattle isolates and 8.7% of human isolates carried antimicrobial resistance genes. The most common resistance genes were those for streptomycin, indicating a shared resistance pattern between cattle and human isolates.

In the second study between 2007 to 2015, an estimated 77.5% of human E. coli infections originated from cattle strains. Eleven persistent bacterial lineages were identified in Alberta, which were responsible for 36.4% of human infections. These lineages continued to cause a significant number of human illnesses through 2018 and 2019, with six of these lineages linked to 74.7% of reported cases during these years. A shift in the toxin profiles of the persistent strains was also noted. Initially, most strains carried both stx1a and stx2a toxins. Over time, there was a significant increase in strains carrying only the more virulent stx2a toxin, which is associated with more severe disease outcomes in humans.

What It Means

Based on the genomic analysis of Canadian isolates from cattle and humans clinical samples, the discriminatory genetic loci predominantly present in clinical isolates have been identified. Further studies on the stability of those traits, these genomic signatures can be employed for food safety screening and monitoring of STEC O157:H7 in both farm and clinical environments. These findings are crucial for developing better screening methods for Shiga toxin and its associated phages, as well as monitoring antimicrobial resistance in both cattle and human isolates.

Additionally, this work provides crucial insights into the persistent transmission of E. coli O157 between cattle and humans in Alberta. The findings highlight the significant role of cattle in spreading the bacteria to humans and the presence of local bacterial strains that have evolved and persisted over many years. The shift towards more virulent strains underscores the need for ongoing monitoring and targeted interventions to control the spread of this pathogen and reduce the incidence of severe infections.