Get aminoacids is not modified by ETA and DT, thus protecting cells from DT- or ETA-mediated cell death. Besides its antimicrobial activity, several lines of evidence suggest an additional regulatory role for HNP-1 when it is not recognized as a substrate, as described for ART5 and ART1. Here we showed that HNP-1 is able to reduce NarE transferase activity. This reduction is more evident at high concentrations of HNP-1, likely to be present in the site of inflammation. Of note the NADase activity, a reaction not usually involved in the toxicity process, is not affected. On the other hand, auto-ADP-ribosylation, which could be an intramolecular mechanism regulating the two activities is enhanced. Although physiological substrates for CT and LT are well known and the extent of modification is limited, members of the antimicrobial peptide family may serve as novel substrates for these ADP-ribosylating toxins. At the onset of infection, bacterial Vismodegib pathogens have evolved different countermeasures to limit the effectiveness of antimicrobials and to counteract the immune system. The modification of antimicrobial components of the innate immune system by bacterial ADP-ribosylating toxins may represent a mechanism that could facilitate bacterial colonization. In the context of the primary immune response, the ADP-ribosylation of HNP-1 may affect both the anti-microbial weapons released by neutrophils and the interplay between inflammatory cells, eventually facilitating the onset of an infectious disease. Hence, our study showing arginine-specific ADP-ribosylation of human defensins catalyzed by some bacterial toxins may be relevant in the onset of infectious diseases. Prostate cancer is the most frequently diagnosed male cancer and the second leading cause of cancer death in men in the United States. Each year in the US, there are approximately 230,000 new cases of prostate cancer and approximately 195,000 radical prostatectomies are performed. However, few patients may be saved by these treatments because only a minority of cases will die of the disease if left untreated. The number needed to treat to save one life estimated in two studies was 12–15 and up to 48. Numerous nomograms and related prediction methods have been created based on clinical variables at the time of diagnosis but, to date, such tools have provided limited advice regarding which patients harbor aggressive disease requiring radical treatment possibly followed by adjuvant therapy and which patients may be suitable for a more conservative active surveillance program. Enormous efforts have been invested in the development of biomarkers for prognosis of prostate cancer with an emphasis on features of the tumor epithelial component in retrospective samples. However, few accepted and clinically employed biomarkers have been developed. One barrier to biomarker discovery may be the cell-type heterogeneity and the polyclonal/multifocal nature of the accumulated genetic alterations at the time of diagnosis. In contrast, the tumor microenvironment exhibits much more limited mutations and loss of heterozygosity but may respond to paracrine signals from nearby tumor.With distinct expression profiles which correlate with poor outcome. Indeed, we have demonstrated that tumorassociated stroma without regard to subtype possesses unique expression profiles when compared to normal stroma. We used these gene expression changes to develop a classifier that can accurately diagnose the presence of tumor in prostate cancer cases even if the samples used for analysis do not contain recognizable tumor. This approach has clinical potential for resolving hundreds of thousands of ambiguous biopsies performed in the US every year.