From gut colonization to recurrence: E. coli secretion systems at the host-microbiota interface.

Escherichia coli occupies a unique position between commensal colonization and infection. It is a common member of the intestinal microbiota, yet selected pathogenic or opportunistic lineages can persist in mucosal niches, interact with resident microbial communities, and in some cases seed recurrent extraintestinal diseases. The mechanisms enabling long-term colonization, survival under host and antibiotic pressure, and relapse are diverse, depending on pathotype, infection site, host environment, and microbial community structure. Here, we critically examine how T3SS, T5SS, and T6SS may contribute to persistence-associated biology in specific E. coli contexts. T3SS primarily mediates epithelial interaction in enteric pathotypes, T5SS drives adhesion, biofilm formation, mucosal colonization, and immune modulation, and T6SS functions as a microbiota-facing mechanism of interbacterial competition. We distinguish experimentally demonstrated roles from speculative links to chronicity and recurrence, framing these systems as context-dependent interaction modules rather than a unified network, while highlighting evidence gaps relative to established persistence determinants.