Internalization, distribution, and activity of peptide H2 against the intracellular multidrug-resistant bovine mastitis-causing bacterium Staphylococcus aureus
Internalization, distribution, and activity of peptide H2 against the intracellular multidrug-resistant bovine mastitis-causing bacterium Staphylococcus aureus
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肽 H2 对细胞内多重耐药牛乳腺炎致病菌金黄色葡萄球菌的内化、分布和活性
DOI：
10.1038/s41598-019-44459-x
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发表时间：
2019-05
影响因子：
4.6
通讯作者：
Wang Jianhua
中科院分区：
文献类型：
--
作者：
Wang Xiao;Teng Da;Wang Xiumin;Hao Ya;Chen Huixian;Mao Ruoyu;Wang Jianhua
牛乳腺炎主要由金黄色葡萄球菌引起，金黄色葡萄球菌难以消灭，易从抗菌剂中逃逸，因其感染的胞内性和耐多药性，可能引起反复感染。本研究在牛乳腺上皮细胞MAC-T细胞和小鼠乳腺中研究了NZ2114衍生物肽H18R （H2）对耐甲氧西林金黄色葡萄球菌（MRSA）和耐多药牛金黄色葡萄球菌的胞内活性。H2对金黄色葡萄球菌的最低抑制浓度为0.5 ~ 1 μg/ml；H2比其亲本肽NZ2114表现出更低的细胞毒性（MAC-T细胞存活率：H2处理为100%，NZ2114 （256 μg/ml）处理为60.7%）。H2主要通过网格蛋白介导的内吞作用内化到MAC-T细胞中，并分布在细胞质中。对MRSA ATCC43300、乳腺炎分离株金黄色葡萄球菌CVCC 3051和E48的细胞内抑制率分别大于99%、99%和94%；这些高于万古霉素组（23-47%）。在金黄色葡萄球菌e48诱导的乳腺炎小鼠模型中，100 μg H2和万古霉素处理后，每个乳腺的细菌数量分别减少3.96和1.59 log CFU。此外，与NZ2114和万古霉素类似，H2减轻了乳腺组织的病理损伤和肺泡内多形核中性粒细胞的浸润。这些结果表明，H2可以作为治疗金黄色葡萄球菌性乳腺炎的安全有效的候选药物。
Bovine mastitis is mainly caused by Staphylococcus aureus, which is difficult to eliminate, prone to escape from antibacterial agents, and may cause recurring infections due to the intracellular nature of its infection and multidrug resistance. In this study, the intracellular activities of the NZ2114 derivative peptide H18R (H2) against methicillin-resistant S. aureus (MRSA) and multidrug-resistant bovine S. aureus strains were investigated in bovine mammary epithelial MAC-T cells and mouse mammary glands. The minimum inhibitory concentrations of H2 against S. aureus were 0.5‒1 μg/ml; H2 displayed a lower cytotoxicity than its parental peptide NZ2114 (survival rates of MAC-T cells: 100% [H2 treatment] vs 60.7% [NZ2114 (256 μg/ml) treatment]). H2 was internalized into MAC-T cells mainly via clathrin-mediated endocytosis, and distributed in the cytoplasm. The intracellular inhibition rates against MRSA ATCC43300, the mastitis isolates S. aureus CVCC 3051 and E48 were above 99%, 99%, and 94%, respectively; these were higher than those in case of vancomycin (23–47%). In the mouse model of S. aureus E48-induced mastitis, after treatment with 100 μg of H2 and vancomycin, bacterial numbers in each mammary gland were reduced by 3.96- and 1.59-log CFU, respectively. Additionally, similar to NZ2114 and vancomycin, H2 alleviated the histopathological damage of the mammary tissue and polymorphonuclear neutrophil infiltration in the alveoli. These results suggest that H2 can be used as a safe and effective candidate for treating S. aureus-induced mastitis.
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影响因子：
5
作者：
Yong Zhang;D. Teng;Xiumin Wang;R. Mao;Xintao Cao;Xiaoyuan Hu;Lifen Zong;Jianhua Wang
通讯作者：
Yong Zhang;D. Teng;Xiumin Wang;R. Mao;Xintao Cao;Xiaoyuan Hu;Lifen Zong;Jianhua Wang
影响因子：
3.4
作者：
Wang, Liangliang;Si, Wei;Zhao, Xin
通讯作者：
Zhao, Xin
影响因子：
3.3
作者：
W. Mamo;M. Lindahl;P. Jonsson
通讯作者：
W. Mamo;M. Lindahl;P. Jonsson
DOI：
--
发表时间：
1981
期刊：
--
影响因子：
--
作者：
W. Hildemann
通讯作者：
W. Hildemann
影响因子：
64.8
作者：
Mygind, PH;Fischer, RL;Kristensen, HH
通讯作者：
Kristensen, HH