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Tuesday, August 15, 2006 Commensal and Pathogen: Not So Black and White Anymore  Move over HPV and EBV, viruses are no longer the only microbes that can mess with your DNA. In a recent Science paper by Nougayrède et al., Escherichia coli was found to induce DNA damage in eukaryotic cells.E. coli is well-known for being the workhorse of the molecular cell biologist and one of the usual residents of the gut microflora. Some E. coli also cause disease. So far, so good--we know that some strains live in relative harmony in our digestive tract and other strains make us sick. But from the observations of Nougayrède et al., this distinction isn't so cut and dried. E. coli is a bit of a Jekyll and Hyde--what some strains consider an aid for surviving harmoniously with a host, others use as virulence factors. When E. coli was added to different mammalian cells, the researchers noticed that the commensal strains and the strains isolated from meningitis and urinary tract infections caused a decidedly different reaction to the cells than laboratory or enteropathogenic/enterohemorrhagic strains. Adding certain E. coli strains caused the host cells to undergo megalocytosis--in other words, the cell became terribly bloated and ceased to divide. This phenomenom was not seen when the mammalian cells were incubated with dead bacteria or when the bacteria were separated from the cells with a 0.2 mm permeable membrane. The cause of megalocytosis, then, was not caused by any toxin that the E. coli was excreting but from something happening during direct bacteria to cell contact. Nougayrède et al. discovered that E. coli induced megalocytosis required a set of genes which they called the "pks island." This genomic island contains the instructions needed to make peptide-polyketide hybrid compounds--nonribosomal peptide megasynthases (NRPs) and polyketide megasynthases (PKs). NRPs and PKs are also produced by other bacteria and fungi, some of which are used for therapeutic agents. At any rate, the compounds made by E.coli aren't so nice. Here, it wreaks havoc on genomic stability as a genotoxin. The pks island allows the bacterium to deliver its PK-NRP hybrid compound to the eukaryotic cell which causes DNA double-strand breaks. When DNA damage is induced, a cellular signaling pathway is activated to halt the cell cycle. Ultimately, cells enlarge and then die. Further survey of different E. coli strains revealed that the pks island was only found in the B2 group of E. coli which contains commensal strains as well as strains that cause disease outside of the intestine. Nougayrède et al. speculate that the pks island acts as a fitness factor enabling the bacteria to stop the cell cycle to effectively colonize the host. Because different strains make different amounts of genotoxin this may affect whether a particular strain can live as a harmless commensal or a pathogen as well as being a possible link to intestinal cancer. [posted by S. Y. Affolee on 8:39 AM : ]
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