Escherichia coli (E. coli), a prevalent commensal bacterium within the resident gut microbiota, includes pathogenic strains that are a leading cause of infant diarrhea in developing countries. In light of the rising antibiotic resistance associated with diarrhea treatment, conventional antibiotic therapies are encountering increasing challenges, underscoring the urgent need for novel therapeutic strategies. The pathogenicity of E. coli is primarily mediated by virulence factors, which play critical roles in facilitating intestinal adhesion and colonization during the early stages of infection. This article reviews recent research progress on E. coli colonization and infection, including its classification, epidemiology, and molecular mechanisms underlying its pathogenicity. It focuses on analyzing the effects of relevant virulence factors and the DcuSR two-component system on the adhesion and colonization of E. coli. Furthermore, the article delves into the impact of hyaluronic acid (HA) on E. coli infection, offering novel insights into the management of E. coli infections.