Abstract
Cationic antimicrobial peptides (CAMPs) occur naturally in numerous organisms and are considered as a class of antibiotics with promising potential against multi-resistant bacteria. Herein, we report a strategy that can lead to the discovery of novel small CAMPs with greatly enhanced antimicrobial activity and retained antibiofilm potential. We geared our efforts towards i) the N-terminal cysteine functionalization of a previously reported small synthetic cationic peptide (peptide 1037, KRFRIRVRV-NH2), ii) its dimerization through a disulfide bond, and iii) a preliminary antimicrobial activity assessment of the newly prepared dimer against Pseudomonas aeruginosa and Burkholderia cenocepacia, pathogens responsible for the formation of biofilms in lungs of individuals with cystic fibrosis. This dimer is of high interest as it does not only show greatly enhanced bacterial growth inhibition properties compared to its pep1037 precursor (up to 60 times), but importantly, also displays antibiofilm potential at sub-MICs. Our results suggest that the reported dimer holds promise for its use in future adjunctive therapy, in combination with clinically-relevant antibiotics.
Highlights
Antibiotic resistance is a serious and growing phenomenon, as well as a primary public health concern [1, 2]
The ability of cys-pep1037 dimer to inhibit the growth of P. aeruginosa was evaluated by determining its minimum inhibitory concentration (MIC) against two different strains of P. aeruginosa, notably ATCC 27853 and ATCC 15442, and results were compared to the Minimum Inhibitory Concentration (MIC) of native pep1037 against the same strains
MIC values determined for pep1037 were in agreement with previously reported MIC values of the same peptide against two Gram-negative pathogens, P. aeruginosa (PAO1 and PA14) and B. cenocepacia (4813), from 304 to > 608 μg/ mL, respectively [19]
Summary
Antibiotic resistance is a serious and growing phenomenon, as well as a primary public health concern [1, 2]. New resistance mechanisms have emerged, making generations of antibiotics virtually ineffective, resulting in prolonged illness, greater risk of death and higher costs. Development of new antibiotics and other novel strategies are critically needed. Biofilm-associated bacteria possess 10–1,000 fold greater resistance to antibiotic treatment compared to freely-floating, planktonic cells, making established biofilm infections especially difficult to eradicate [3, 4]. The severe antibiotic resistance of Pseudomonas aeruginosa and Burkholderia cenocepacia in lungs of Cystic Fibrosis (CF) patients has been associated with the formation of drug resistant biofilms [6, 7].
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