Targeted depletion of pks + bacteria from a fecal microbiota using specific antibodies.

The island is one of the most prevalent pathogenicity islands among the strains that colonize the colon of colorectal carcinoma (CRC) patients. This pathogenic island encodes the production of a nonribosomal polyketide-peptide named colibactin, which induces double-strand breaks in DNA molecules. Detection or even depletion of this -producing bacteria could help to understand the role of these strains in the context of CRC. In this work, we performed a large-scale screening of the cluster in more than 6,000 isolates of . The results obtained reveal that not all the -detected strains could produce a functional genotoxin and, using antibodies against -specific peptides from surface cell proteins, a methodology for detection and depletion of + bacteria in gut microbiotas was proposed. With our method, we were able to deplete a human gut microbiota of this + strains, opening the door to strain-directed microbiota modification and intervention studies that allow us to understand the relation between these genotoxic strains and some gastrointestinal diseases.IMPORTANCEThe human gut microbiome has also been hypothesized to play a crucial role in the development and progression of colorectal carcinoma (CRC). Between the microorganisms of this community, the strains carrying the genomic island were shown to be capable of promoting colon tumorigenesis in a colorectal cancer mouse model, and their presence seems to be directly related to a distinct mutational signature in patients suffering CRC. This work proposes a novel method for the detection and depletion of -carrying bacteria in human gut microbiotas. In contrast to methods based on probes, this methodology allows the depletion of low-abundance bacterial strains maintaining the viability of both targeted and non-targeted fractions of the microbiota, allowing the study of the contribution of these -carrying strains to different diseases, such as CRC, and their role in other physiological, metabolic or immune processes.