Thamri Amal, Létourneau Myriam, Djoboulian Alex, Chatenet David, Déziel Eric, Castonguay Annie, Perreault Jonathan
INRS - Institut Armand-Frappier, Université du Québec, Laval, Québec, Canada.
PLoS One. 2017 Mar 15;12(3):e0173783. doi: 10.1371/journal.pone.0173783. eCollection 2017.
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.
阳离子抗菌肽（CAMPs）天然存在于众多生物体中，被认为是一类对抗多重耐药细菌具有潜在应用前景的抗生素。在此，我们报告一种策略，该策略可用于发现新型的小阳离子抗菌肽，其抗菌活性显著增强且保留了抗生物膜潜力。我们致力于：i）对先前报道的一种小合成阳离子肽（肽1037，KRFRIRVRV-NH2）进行N端半胱氨酸功能化；ii）通过二硫键使其二聚化；iii）对新制备的二聚体针对铜绿假单胞菌和洋葱伯克霍尔德菌进行初步抗菌活性评估，这两种病原体可在囊性纤维化患者肺部形成生物膜。这种二聚体备受关注，因为与它的pep1037前体相比，它不仅表现出显著增强的细菌生长抑制特性（高达60倍），而且重要的是，在亚抑菌浓度下也具有抗生物膜潜力。我们的结果表明，所报道的二聚体有望与临床相关抗生素联合用于未来的辅助治疗。
