The identification and characterization of a novel CAMP from Stf76, a Sulfolobus islandicus plasmid-virus pSSVx transcription factor

The increasing resistance of bacteria to classical types of antibiotics has become a serious problem in the health community dealing with infectious diseases. As more strains of pathogenic bacteria become resistant to antibiotics, the need to develop new antimicrobial agents becomes more critical. Antimicrobial peptides have been viewed as possible alternatives to classical antibiotics1, however, their use has yet to become widespread because more research on discovering their exact mechanism of action is needed. The cationic antimicrobial peptides (CAMPs) are an interesting class of antibacterial molecules that could overcome the problem of multi-drug resistance because they are an essential component of the innate immune response of multicellular eukaryotes. Furthermore they show very advantageous properties: they are relatively small molecules with a broad spectrum of activity (Gram +, Gram -, yeasts and fungi) on both dividing and resting cells; they are able to damage bacterial membranes, thus reducing the onset of resistant strains. Moreover they have an effective action on mature biofilms (another important resistant factor) and possess additional immunomodulatory properties that include chemotaxis, induction of cytokine release, regulation of angiogenesis and anti-inflammatory activity. Thus, CAMPs could be considered as a bridge between innate and adaptive immunity. A quantitative prediction of antibacterial activity and the localization of a CAMP within the sequence of a well characterized DNA-binding protein Stf76 from the Sulfolobus islandicus plasmid-virus pSSVx2 has been performed by means of bioinformatic tools. Once identified the peptide, here named PepC, it has been characterized from a structural and a functional point of view. Antimicrobial assays on a wide range of microorganisms have been performed. Far-UV circular dichroism spectra of PepC alone and in the presence of different detergents have been registered highlighting a propensity to form helical structure. Moreover, PepC showed a significantly greater fusion activity in DOPE/DOPG LUVs compared with the fusion activity in DOPC/DOPG LUVs. In addition leakage assays showed a capability of PepC-induced pore formation. All the results will be widely discussed. References 1. Rezansoff AJ, et al J Pept Res. 2005 May;65(5):491-501.. 2. Contursi P., Pirone L.; Farina B. et al. Nucleic Acids Res. 2014 Mar 25. 3. Galdiero S, et al. Int J Mol Sci. 2013 Sep12;14(9):18758-89.