Functional Genomics of Gastrointestinal Isolated from Patients with Cancer and Diarrhea.

TitleFunctional Genomics of Gastrointestinal Isolated from Patients with Cancer and Diarrhea.
Publication TypeJournal Article
Year of Publication2023
AuthorsCarter, H, Clark, J, Carlin, LG, Vaughan, E, Rajan, A, Olvera, A, Yu, X, Zeng, X-L, Kambal, A, Holder, M, Qin, X, Gibbs, RA, Petrosino, JF, Muzny, DM, Doddapaneni, H, Menon, VK, Hoffman, KL, Meng, Q, Ross, MC, Cregeen, SJJavornik, Metcalf, G, Jenq, R, Blutt, S, Estes, MK, Maresso, A, Okhuysen, PC
Corporate AuthorsTMC-GCID team
Date Published2023 Jun 01

We describe the epidemiology and clinical characteristics of 29 patients with cancer and diarrhea in whom Enteroaggregative (EAEC) was initially identified by GI BioFire panel multiplex. strains 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 diverse groups 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 GI , but also compared to prototype strains of other diarrheagenic . Some of the diverse strains 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 GI isolates and observed a positive correlation between adherence to colonoids and the number of metal acquisition genes carried in both EAEC and the diverse strains. This work indicates that from 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-define pathotypes with greater diagnostic accuracy and into more clinically relevant groupings.

Alternate JournalbioRxiv
PubMed ID37398483
PubMed Central IDPMC10312547
Grant ListU19 AI116497 / AI / NIAID NIH HHS / United States
U19 AI144297 / AI / NIAID NIH HHS / United States