Abstract
AbstractWe describe the epidemiology and clinical characteristics of 29 patients with cancer and diarrhea in whom EnteroaggregativeEscherichia coli(EAEC) was initially identified by GI BioFire panel multiplex.E. colistrains were successfully isolated from fecal cultures in 14 of 29 patients. Six of the 14 strains were identified as EAEC and 8 belonged to other diverseE. coligroups of unknown pathogenesis. We investigated these strains by their adherence to human intestinal organoids, cytotoxic responses, antibiotic resistance profile, full sequencing of their genomes, and annotation of their functional virulome. Interestingly, we discovered novel and enhanced adherence and aggregative patterns for several diarrheagenic pathotypes that were not previously seen when co-cultured with immortalized cell lines. EAEC isolates displayed exceptional adherence and aggregation to human colonoids compared not only to diverse GIE. coli, but also compared to prototype strains of other diarrheagenicE. coli. Some of the diverseE. colistrains that could not be classified as a conventional pathotype also showed an enhanced aggregative and cytotoxic response. Notably, we found a high carriage rate of antibiotic resistance genes in both EAEC strains and diverse GIE. coliisolates and observed a positive correlation between adherence to colonoids and the number of metal acquisition genes carried in both EAEC and the diverseE. colistrains. This work indicates thatE. colifrom cancer patients constitute strains of remarkable pathotypic and genomic divergence, including strains of unknown disease etiology with unique virulomes. Future studies will allow for the opportunity to re-defineE. colipathotypes with greater diagnostic accuracy and into more clinically relevant groupings.
Publisher
Cold Spring Harbor Laboratory