Travé-Asensio Sergi, Tort-Miró Aida, Pinheiro Silvana, Garcia-Fruitós Elena, Arís Anna, Zamora William J
IRTA, Ruminant Production, Torre Marimon, Caldes de Montbui, Catalonia, Spain.
CBio3 Laboratory, School of Chemistry, University of Costa Rica, San José, Costa Rica.
Microb Biotechnol. 2025 Sep;18(9):e70204. doi: 10.1111/1751-7915.70204.
Host defence peptides (HDPs) represent a valuable class of antimicrobial agents with the potential to address the growing threat of antimicrobial resistance (AMR). Here, we have studied recombinant constructs based on a combination of HDPs fused to the GFP protein and multidomain proteins combining three or four HDPs in a single polypeptide, referred to as first and second generation antimicrobials, respectively. These recombinant peptides were tested against Gram-positive and Gram-negative bacteria associated with healthcare infections. In addition, in silico studies provided insight into the antimicrobial structure-activity relationships of these biomolecules. For the first generation of antimicrobials, amphipathicity mainly explains the average antimicrobial activity against the Gram-positive strains. In the case of the Gram-negative bacteria, it depends on the quantity and the exposed area of the Ser and Thr amino acids. For the second generation of antimicrobials, the order of domains is crucial to act against Gram-positive strains, preferably by positioning the most bioactive domain against the Gram-positive pathogen at the ends.
宿主防御肽（HDPs）是一类有价值的抗菌剂，有潜力应对日益严重的抗菌药物耐药性（AMR）威胁。在此，我们研究了基于与绿色荧光蛋白（GFP）融合的HDP组合的重组构建体，以及在单个多肽中结合三个或四个HDP的多结构域蛋白，分别称为第一代和第二代抗菌剂。这些重组肽针对与医疗保健感染相关的革兰氏阳性菌和革兰氏阴性菌进行了测试。此外，计算机模拟研究深入了解了这些生物分子的抗菌构效关系。对于第一代抗菌剂，两亲性主要解释了对革兰氏阳性菌株的平均抗菌活性。对于革兰氏阴性菌，这取决于丝氨酸（Ser）和苏氨酸（Thr）氨基酸的数量和暴露面积。对于第二代抗菌剂，结构域的顺序对于对抗革兰氏阳性菌株至关重要，最好是将最具生物活性的结构域定位在对抗革兰氏阳性病原体的末端。
