Challenges and Accomplishments in Tackling Enteropathogenic E. Coli

By: Austin Weynand, MHS

Logo for the Latin American Coalition for E. Coli Research (LACER)

Dr. Alfredo Torres has his mind set on one thing: To understand, treat, and prevent pathogenic E. Coli. As a prominent scientist at UTMB with a background in microbiology and immunology, he has spent years running a lab which approaches the E. Coli challenge from multiple angles. The spectrum of his work begins with basic bioinformatics research on E. Coli strains and continues all the way to animal model studies in the pre-clinical phases of vaccine development.

According to Dr. Torres, the pathway to vaccine development is arduous but rewarding. First, it involves foundational research; they use immunoinformatic approaches to identify antigen candidates in the E. Coli genome. Later, his lab will investigate positive properties of an antigen candidate, explore immunogenicity, and apply these to rodent animal models (mice, as Dr. Torres explains, are more viable than primates or another model because pathogenic E. Coli actually causes disease in them). The mice are challenged with the pathogen itself and then observed for reductions in colonization post-immunization. To advance to human trials, a candidate must then demonstrate safety, effectiveness, and measurable correlates of immunity.

The prospect of a Torres vaccine candidate advancing to clinical trials in the Sealy Institute for Vaccine Sciences is exciting – but it’s not the sole solution to E. Coli epidemics. Dr. Torres explains that this is a major One Health challenge, particularly in Latin and South America. Argentina, for example, has more cases of E. Coli O157:H7 than almost any other nation, which comes primarily from the consumption of infected beef cattle.1 There was an animal vaccine to prevent pathogen proliferation in cattle, but according to Dr. Torres, it was expensive, and pharma companies became disinterested in this angle of prevention. Moreover, farms that raise and sell these animals often shy away from research collaboration because E. Coli strains often do not cause disease in them.

E. Coli can spread in other animals too – from rats and birds to cattle and swine. The route of transmission in some scenarios is consumption of the meat, but in others, E. Coli spreads via feces. There are environmental sources of the bacteria that propagate the life cycle in such animals, and little research focused on this connection. There is evidence for growing antibiotic resistance in these bacteria, often through horizontal gene transfer.2 Lastly, and perhaps most importantly, mutant strains of E. Coli have begun to emerge, particularly during the COVID-19 era.3 Pathogens appear to exchange genetic information as they interact in animal reservoirs or in the environment, leading to greater virulence and ability to disseminate. “We are seeing enterohemorrhagic E. Coli that expresses enteropathogenic genes, and vice versa,” Dr. Torres explains. One multidisciplinary group, called the Latin American Coalition for Escherichia coli Research (LACER), is working to establish connections between the epidemiologic, scientific, and public health aspects of E. Coli.4

The key to tackling this multifaceted problem is largely a One Health approach. Entities must invest in better treatment availability in afflicted nations, better targeting of animal reservoirs, and, of course, vaccine development. At this time, Dr. Torres and his lab have identified two targetable antigens that can attack certain strains, including 10 isolates of pathogenic E. Coli. If effectiveness is proven in his pre-clinical trials, he hopes to soon see his vaccine candidates studied in humans. You can read more about his research and recent publications here.

  1. Torti, J. F., Cuervo, P., Nardello, A., & Pizarro, M. (n.d.). Epidemiology and Characterization of Shiga Toxin-Producing Escherichia Coli of Hemolytic Uremic Syndrome in Argentina. Cureus, 13(8), e17213. https://doi.org/10.7759/cureus.17213

  2. Poirel, L., Madec, J.-Y., Lupo, A., Schink, A.-K., Kieffer, N., Nordmann, P., & Schwarz, S. (2018). Antimicrobial Resistance in Escherichia coli. Microbiology Spectrum, 6(4). https://doi.org/10.1128/microbiolspec.ARBA-0026-2017

  3. Nascimento, J. A. S., Santos, F. F., Valiatti, T. B., Santos-Neto, J. F., M. Santos, A. C., Cayô, R., Gales, A. C., & A. T. Gomes, T. (2021). Frequency and Diversity of Hybrid Escherichia coli Strains Isolated from Urinary Tract Infections. Microorganisms, 9(4), 693. https://doi.org/10.3390/microorganisms9040693

  4. Torres, A. G. (2017). Escherichia coli diseases in Latin America-a “One Health” multidisciplinary approach. Pathogens and Disease, 75(2). https://doi.org/10.1093/femspd/ftx012

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