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抗菌效力的体内设计的细胞穿透肽对多重耐药菌株的肠炎沙门氏菌和鼠伤寒沙门氏菌。

Antibacterial efficacy of in-house designed cell-penetrating peptide against multi-drug resistant strains of Salmonella Enteritidis and Salmonella Typhimurium.

机构信息

Division of Veterinary Public Health, ICAR-Indian Veterinary Research Institute, Izatnagar, Uttar Pradesh, 243 122, India.

Department of Veterinary Public Health, Bihar Veterinary College, Bihar Animal Sciences University, Patna, Bihar, 800 014, India.

出版信息

Environ Microbiol. 2022 Jun;24(6):2747-2758. doi: 10.1111/1462-2920.15778. Epub 2021 Sep 23.

Abstract

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 ) 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.

摘要

我们评估并比较了一种新型细胞穿透肽(CPP)变体 Cecropin A(1-7)-Melittin(CAMA)(CAMA-CPP)与两种已鉴定的 CPP(P7 和 APP)对已确定的多药耐药(MDR)肠炎沙门氏菌和鼠伤寒沙门氏菌的体外抗菌功效,同时以 CAMA 作为对照。首先,确定了 CAMA-CPP、APP 和 CAMA 的最低抑菌浓度(MIC)(μg/ml)分别为 3.91、7.81 和 3.91,而 P7 的 MIC 为 7.81;然而,所有肽的最低杀菌浓度(MBC)均为 MIC 的两倍。与其他 CPP 相比,CAMA-CPP 和 CAMA 在不同条件(高温、蛋白酶-K、阳离子盐、pH 值和血清)下均稳定。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和绵羊及人红细胞的溶血作用,对共生肠道乳杆菌也无不良影响。体外时效杀菌试验表明,CAMA-CPP 和 APP 的 MBC 水平可消除哺乳动物细胞系中的细胞内 MDR 沙门氏菌感染;然而,CAMA 和 P7 肽无效。CAMA-CPP 似乎是一种很有前途的抗菌候选物,并为其体内临床转化开辟了新的途径。

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