Abstract
Accumulating evidence indicates that the human intestinal microbiota can contribute to the etiology of colorectal cancer. Triggering factors, including inflammation and bacterial infections, may favor the shift of the gut microbiota from a mutualistic to a pro-carcinogenic configuration. In this context, certain bacterial pathogens can exert a pro-tumoral activity by producing enzymatically-active protein toxins that either directly induce host cell DNA damage or interfere with essential host cell signaling pathways involved in cell proliferation, apoptosis, and inflammation. This review is focused on those toxins that, by mimicking carcinogens and cancer promoters, could represent a paradigm for bacterially induced carcinogenesis.
Highlights
Nowadays, the human body is worldwide recognized as the home to a complex community, crowded and various, composed by at least 100 trillion microbial cells [1] that have certainly coexisted with their host since the most ancient times [2] (Figure 1)
Certain bacterial pathogens can exert a pro-tumoral activity by producing enzymatically-active protein toxins that either directly induce host cell DNA damage or interfere with essential host cell signaling pathways involved in cell proliferation, apoptosis, and inflammation
Genome instability is most readily caused by bacterial protein toxins that trigger host cell double-strand DNA breaks (DSBs), such as the cytolethal distending toxin (Cdt) and the colibactin (Figure 3A,B)
Summary
The human body is worldwide recognized as the home to a complex community, crowded and various, composed by at least 100 trillion microbial cells [1] that have certainly coexisted with their host since the most ancient times [2] (Figure 1). The microbial ecosystem that resides in and on the human body constitutes, collectively, the microbiota, and the genes encoded are known as the microbiome. The gut microbiota from the Hadza, a community of Tanzanian hunter–gatherers whose lifestyle closely resembles that of Paleolithic humans, may furnish interesting clues on the co-evolution of microbiota–human host. IGnetnhoismreviineswta, bielsitiydeissumpdoastinregaoduilrypcraevuisoeuds breyvibeawctoenriathl epsraomteeintotpoixci[n2s3]t,hwate wtrigllgdeirschuossthcoewll tdhoeuebnleco-sutrnatnerdoDf NprAotbeirneavkirsu(lDenScBes)f,ascutocrhs apsrothdeucyedtobleythgaultdbiastcetenrdiainwgittohxhinos(tCcdetl)lsamndaythreescuolltibinactthine m(Faignuipreu3laAti,oBn).of crucial host cell pathways involved in cancer onset
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