Selection, Comparative Genomics, and Potential Probiotic Features of Escherichia coli 5C, a pks-Negative Strain Isolated from Healthy Infant Donor Feces

Among the emerging issues in probiotic safety, the possible presence of pks, a gene cluster synthetizing a genotoxin known as colibactin, is one of the most alarming. Indeed, indigenous E. coli strain pks-positive are found in 60% of patients with colorectal cancer, and the most widely used E. coli-based probiotic, known as E. coli Nissle 1917 (DSM 6601), is pks-positive. Starting from 25 potential candidates selected by screening 25 infant stool samples, we have selected an E. coli strain (named 5C, deposited as LMG S-33222) belonging to the phylotype A and having the serovar O173:H1. Having been previously completely sequenced by our group, we have further characterized this strain, demonstrating that it is (i) devoid of the most known potential pathogenic-related genes, (ii) devoid of possible plasmids, (iii) antibiotic-sensitive according to the EFSA panel, (iv) resistant in gastric and enteric juice, (v) significantly producing acetate, (vi) poorly producing histamine, (vii) endowed with a significant in vitro antipathogenic profile, (viii) promoting a significant in vitro immunological response based on IL-10 and IL-12, and (ix) devoid of the pks genes. A comparative genomics versus E. coli Nissle 1917 is also provided. Considering that the other two most commonly used E. coli-based probiotics (E. coli DSM 17252 and E. coli A0 34/86) are respectively pks-positive and alpha-hemolysin-(hly) and cytotoxic necrotizing factor-1-(cnf1) positive, this novel strain (E. coli 5C) is likely the probiotic E. coli strain with the best safety profile available to date for human use.