Serine phosphorylation of CesT by the type III secretion system effectors NleH1 and NleH2 regulates antagonization of CsrA in enteropathogenic Escherichia coli

Esther Tang ¹, Angeline C Beltran ¹, Senthuran Mahendradeva ¹, Abiali A Badani ¹, Dustin J Little

Like pirates boarding a ship they’re about to raid, food-poisoning bacteria inject proteins into the cells lining our small intestine to hijack them. This creates chaos inside the cell, disrupting its normal functions.

Enteropathogenic E. coli (EPEC), a common cause of diarrheal illness, must deploy these hijacking proteins in a very specific order to ensure infection unfolds properly. This process is controlled by “chaperone” molecules, which act like escorts, picking up the proteins and guiding them to be released into intestinal cells. This paper focuses on one such chaperone: CesT.

Phosphorylation is a common way cells control protein activity, like flipping a molecular switch. By adding a phosphate group, a protein’s behavior can be changed. This study shows that two bacterial proteins, NleH1 and NleH2, phosphorylate CesT. This modifies CesT’s ability to interact with its cargo proteins, affecting how they are delivered.

Overall, this research highlights how EPEC uses multiple layers of control within its microscopic “factory” to ensure its molecular cargo is delivered at the right time and in the right amounts. Insights into these infection mechanisms may guide the development of targeted therapies to treat or prevent EPEC-related disease.