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Antibacterial efficacy of in-house designed cell-penetrating peptide against multi-drug resistant strains of Salmonella Enteritidis and Salmonella Typhimurium
Environmental Microbiology ( IF 5.1 ) Pub Date : 2021-09-16 , DOI: 10.1111/1462-2920.15778
Maria Anto Dani Nishanth 1 , Sirsant Bhoomika 1, 2 , Diksha Gourkhede 1 , Bhargavi Dadimi 1 , Jess Vergis 3 , Satya Veer Singh Malik 1 , Sukhadeo Baliram Barbuddhe 4 , Deepak Bhiwa Rawool 1, 4
Affiliation  

The in vitro antibacterial efficacy of an in-house designed cell-penetrating peptide (CPP) variant of Cecropin A (1–7)-Melittin (CAMA) (CAMA-CPP) against the characterized multi-drug resistant (MDR) field strains of Salmonella Enteritidis and Salmonella Typhimurium were evaluated and compared with two identified CPPs namely, P7 and APP, keeping CAMA as control. Initially, the minimum inhibitory concentration (MIC) (μg ml−1) of in-house designed CAMA-CPP, APP and CAMA was determined to be 3.91, whereas that of P7 was 7.81; however, the minimum bactericidal concentration (MBC) of all the peptides were twice the MIC. CAMA-CPP and CAMA were found to be stable under different conditions (high-end temperatures, proteinase-K, cationic salts, pH and serum) when compared to the other CPPs. Moreover, CAMA-CPP exhibited negligible cytotoxicity in HEp-2 and RAW 264.7 cell lines as well as haemolysis in the sheep and human erythrocytes with no adverse effects against the commensal gut lactobacilli. In vitro time-kill assay revealed that the MBC levels of CAMA-CPP and APP could eliminate the intracellular MDR-Salmonella infections from mammalian cell lines; however, CAMA and P7 peptides were ineffective. CAMA-CPP appears to be a promising antimicrobial candidate and opens up further avenues for its in vivo clinical translation.

中文翻译:

内部设计的细胞穿透肽对肠炎沙门氏菌和鼠伤寒沙门氏菌的多重耐药菌株的抗菌功效

内部设计的 Cecropin A (1-7)-Melittin (CAMA) (CAMA-CPP) 细胞穿透肽 (CPP) 变体对表征的多药耐药 (MDR) 野毒株的体外抗菌功效评估肠炎沙门氏菌鼠伤寒沙门氏菌,并与两种已鉴定的 CPP 即 P7 和 APP 进行比较,以 CAMA 作为对照。最初,最小抑制浓度 (MIC) (μg ml -1) 内部设计的 CAMA-CPP、APP 和 CAMA 确定为 3.91,而 P7 为 7.81;然而,所有肽的最低杀菌浓度(MBC)是MIC的两倍。与其他 CPP 相比,发现 CAMA-CPP 和 CAMA 在不同条件下(高端温度、蛋白酶-K、阳离子盐、pH 和血清)是稳定的。此外,CAMA-CPP 在 HEp-2 和 RAW 264.7 细胞系中表现出可忽略不计的细胞毒性,并且在绵羊和人类红细胞中表现出溶血作用,对共生肠道乳酸杆菌没有不良影响。体外计时杀灭实验表明,CAMA-CPP和APP的MBC水平可以消除细胞内的MDR-沙门氏菌。来自哺乳动物细胞系的感染;然而,CAMA 和 P7 肽无效。CAMA-CPP 似乎是一种很有前途的抗菌候选药物,并为其体内临床转化开辟了进一步的途径。
更新日期:2021-09-16
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