127: E. coli and Burkholderia vaccines with Alfredo Torres

Pathogenic E. coli are different than lab-grown or commensal E. coli found in the gut microbiome. Alfredo Torres describes the difference between these, the method his lab is using the develop vaccines against pathogenic E. coli, and how this same method can be used to develop vaccines against Burkholderia infections.

Julie's Biggest Takeaways:

1. coli plays many roles inside and outside the scientific laboratory:

• Laboratory E. coli strains used by scientists to study molecular biology.
• Commensal E. coli strains contribute to digestion and health as part of the intestinal microbiome.
• Pathogenic E. coli strains have acquired factors that allow them to cause disease in people

The pathogenic E. coli associated with diarrheal disease are the ones named for their O-antigen and flagellar H-antigen, such as O157:H7. There are about 30 E. coli strains with various combinations of O-H factors known to cause diarrheal disease in people.

The E. coli Shiga toxin (though not the bacterium itself) can pass through the epithelial cell layer to become systemic, and eventually the toxin will accumulate in the kidneys. This can lead to patients experiencing hemolytic uremic syndrome (HUS) and kidney failure, leading to lifelong dialysis or need for a transplant. An immune response that prevents the E. coli from attaching will prevent the bacterium from secreting toxin in close proximity to the epithelial cells and decrease likelihood of HUS development.

Burkholderia is a bacterial genus whose member species have been weaponized in the past, and which remain potent disease-causing agents around the world.

• B. mallei causes glanders, a disease mostly of horses and their handlers. It is a respiratory infection that can become systemic if not treated.
• B. pseudomallei causes melioidosis, a disease that can manifest in many ways. It is endemic in many tropical regions around the world, found in over 79 countries so far.

Coating gold nanoparticles with antigens against which the immune response will be protective is a method Alfredo has used for a number of candidate vaccines, including one against E. coli and one against B. pseudomallei. The nanoparticles can have the gold cleaved off to provide different functional variants of the same vaccine.

Links for this Episode:

• Alfredo Torres webpage at University of Texas Medical Branch
• McWilliams BD and Torres AG. Enterohemorrhagic Escherichia coli Adhesins. Microbiology Spectrum. 2013.
• Sanchez-Villamil JI et al. Development of a Gold Nanoparticle Vaccine against Enterohemorrhagic Escherichia coli O157:H7. mBio. 2019.
• Wiersinga WJ et al. Melioidosis. Nature Reviews Disease Primers. 2018.
• Khakhum N. et al. Evaluation of Burkholderia mallei ΔtonB Δhcp1 (CLH001) as a live attenuated vaccine in murine models of glanders and melioidosis. PLOS Neglected Tropical Diseases. 2019.
• Torres AG. Common Sense Can Keep You Safe in E. coli Outbreak. Galveston County Daily News. 2020.
• ABRCMS: Annual Biomedical Research Conference for Minority Students
• MTM: Burkholderia pseudomallei & the neglected tropical disease melioidosis with Direk Limmathurotsakul
• HOM Tidbit: Kiyoshi Shiga Biography in Clinical Infectious Diseases