Enteropathogenic Escherichia coli (EPEC) have developed survival strategies to evade host defense systems. The intracellular level of guanosine tetraphosphate (ppGpp) controlled by RelA and SpoT can mediate immune evasion of EPEC. However, the impact of ppGpp-defective EPEC infection on phagocytes remains unknown. In this study, we report that disrupting relA and spoT of EPEC E2348/69 strain promotes its phagocytosis in porcine macrophages. Our experimental analysis showed that both uptake and killing of an E2348/69 ΔrelAΔspoT mutant by macrophages were increased compared to those of wildtype strain. These results suggest that ppGpp plays an essential role in evading phagocytosis during EPEC pathogenesis.

Enteropathogenic Escherichia coli (EPEC) is one of the etiological agents that causes diarrhea in weaning pigs. In this study, we report that mutating both relA and spoT genes in EPEC E2348/69 can promote bacterial clearance in porcine gastrointestinal tract (GIT). Our experimental analyses showed that an E2348/69 ΔrelAΔspoT mutant strain was not detected in porcine feces after 1 day post-infection (dpi), whereas its parental strain was continuously detected in porcine feces within 10 dpi. Histologic assessment revealed that the mutant strain was unable to induce moderate pathologic lesions in porcine GIT when compared to those with the wildtype strain. Taken together, our data suggest that the relA and spoT genes in EPEC play an important role in bacterial survival and pathogenesis in porcine GIT.