Bacterial sneak attack

Bacteria make a whole range of toxic products that interact in a very precise manner with eukaryotic cellular machinery. These toxins typically interfere with key eukaryotic processes, such as protein synthesis and cellular signalling components. Transient infection of eukaryotic cells with commensal and extraintestinal pathogenic Escherichia coli of phylogenetic group B2 blocks mitosis and induces megalocytosis. This trait is linked to a genomic island that encodes giant modular nonribosomal peptide and polyketide synthases. Polyketides and nonribosomal peptides are extremely large classes of natural products that are assembled from simple acyl-coenzyme A or amino acid monomers. Contact with E. coli expressing this gene cluster causes DNA double-strand breaks and activation of the DNA damage checkpoint pathway, leading to cell cycle arrest and eventually to cell death. This functional nonribosomal peptide polyketide synthase gene cluster is widely distributed in commensal E. coli strains and is even found in a strain used as a probiotic agent. The genotoxic effect may be exploited by the bacteria to slow the rate of renewal of the intestinal epithelium by blocking the cell cycle. These findings may also provide clues about the role of microorganisms in the development of colonic or prostate cancers.