BREAKING INTERINSIC ANTIBIOTIC RESSISTANCE OUTER MEMBRANE-PERMIABLIZING PEPTIDES FROM INNATE BACTERIAL PROTEOMES

Abstract

Intrinsic antibiotic resistance is the innate ability of bacteria to resist antimicrobial agents. The most defining structure that confers intrinsic antibiotic resistance, is the outer membrane of Gram-negative bacteria. It is a highly impermeable barrier that impedes various antibiotics from reaching their targets. A lot of research focuses on finding and developing novel drug candidates with increased antibacterial activity, but less research has been done on selective outer membrane permeabilization compounds. Such compounds could render Gram-negative bacteria susceptible to almost all known antimicrobials. It has been shown that the bacterial proteome is host to proteins containing a membrane-anchoring motif, which exerts selectivity towards the outer membrane. The aim of this Master thesis is to investigate the outer membrane permeabilizing properties of peptides derived from membrane-binding domains of innate peptides. This is realized through development and optimization of assays to assess the peptides outer and inner membrane activity against Mycobacterium smegmatis In addition, antibacterial activity was tested against both E. coli. Here I show that 16 out of 18 innate peptides derived from M. smegmatis and E.coli are active against the outer membrane of M. smegmatis. Expect peptides SepF11 and SepF14 all the other peptides shown outer membrane permeabilization in Mycobacterium smegmatis which is a very interesting finding and can be further used to solve the the problem of membrane permeabilising by antibiotics and may be used to solve the antibiotic resistance exist in MDR strains of Mycobacterium tuberculosis.