טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
M.Sc Thesis
M.Sc StudentOhad Meir
SubjectCharacterization of C14KKc12K: A Miniature Bactericidal
Lipopeptide with Anti-Biofilm Properties
DepartmentDepartment of Biotechnology and Food Engineering
Supervisors Full Professors Mor Amram
Professor Emeritus Cogan Uri
Full Thesis textFull thesis text - English Version


Abstract

The wide spread occurrence of multi drug resistant bacteria combined with the dwindling supply of efficacious antibacterials, is a growing worldwide concern for Human health. In addition, the prevalence of bacterial biofilms in the medicinal and industrial arenas poses an even greater challenge. Membrane active compounds, exerting antibacterial activities through non-specific modes of action are considered attractive candidates for de-novo design of new antimicrobial agents. Namely, the peptidomimetic family of oligo-acyl-lysyls was investigated for its ability to mimic host defense peptides. Here, C14KKc12K (i.e. myristoyl-lysyl-lysyl-aminolauryl-lysyl-amide), a representative of this peptidomimetic family was studied with respect to its physical, antibacterial and mechanistic properties. Tested against more than 50 bacterial strains, C14KKc12K was found to have broad-spectrum of activity, with minimal inhibitory concentrations in the low micro-molar range against Gram positive and Gram negative bacteria. Its bactericidal mode of action was shown to resemble the characteristic actions exerted by host defense peptides, through damaging the membranes of both Gram positive and Gram negative bacteria. C14KKc12K was demonstrated to have high binding affinity for lipopolysaccharides, much like the gold-standard lipopolysaccharide binder polymyxin B - a cyclic lipopeptide used as last resort antibiotic in the treatment of Gram negative infections. Moreover, C14KKc12K retained its bactericidal activity in complex media such as Human saliva, albeit at higher doses. Nevertheless, its antibacterial potency was equivalent to chlorhexidine, the gold-standard antibacterial agent used in the treatment of oral inflammations. Even when challenged with the treatment of Streptococcus mutans preformed biofilms, C14KKc12K exerted antibacterial activities, equipotent to chlorhexidine. Collectively, the results establish C14KKc12K as the shortest, broad-spectrum bactericidal oligo-acyl-lysyl, and position it on equal terms with commercially used gold-standards.