colibactin and Bacterial-Infections

Mammalian cells possess sophisticated genome surveillance and repair mechanisms, executed by the so-called DNA damage response (DDR), failure of which leads to accumulation of DNA damage and genomic instability. Mounting evidence suggests that bacterial infections can elicit DNA damage in host cells, and certain pathogens induce such damage as part of their multi-faceted infection programme. Bacteria-mediated DNA damage can occur either directly through the formation of toxins with genotoxic activities or indirectly as a result of the activation of cell-autonomous or immune defence mechanisms against the pathogen. Moreover, host-cell signalling routes involved in the DDR can be altered in response to an infection, and this, in the context of DNA damage elicited by the pathogen, has the potential to trigger mutations and cancer.

Topics: Animals; Bacterial Infections; Chlamydia trachomatis; DNA Damage; DNA Repair; Genome, Human; Genomic Instability; Helicobacter pylori; Host-Pathogen Interactions; Humans; Peptides; Polyketides; Shigella flexneri

Prostate adenocarcinoma is the second most commonly diagnosed cancer in men worldwide, and the initiating factors are unknown. Oncogenic TMPRSS2:ERG (ERG+) gene fusions are facilitated by DNA breaks and occur in up to 50% of prostate cancers. Infection-driven inflammation is implicated in the formation of ERG+ fusions, and we hypothesized that these fusions initiate in early inflammation-associated prostate cancer precursor lesions, such as proliferative inflammatory atrophy (PIA), prior to cancer development. We investigated whether bacterial prostatitis is associated with ERG+ precancerous lesions in unique cases with active bacterial infections at the time of radical prostatectomy. We identified a high frequency of ERG+ non-neoplastic-appearing glands in these cases, including ERG+ PIA transitioning to early invasive cancer. These lesions were positive for ERG protein by immunohistochemistry and

Topics: Atrophy; Bacterial Infections; DNA Breaks; Humans; Male; Oncogene Fusion; Peptides; Polyketides; Prostate; Prostatectomy; Prostatic Neoplasms; Prostatitis; Serine Endopeptidases; Transcriptional Regulator ERG