In vitro and in vivo efficacy of combinations of colistin and different endolysins against clinical strains of multi-drug resistant pathogens
In vitro and in vivo efficacy of combinations of colistin and different endolysins against clinical strains of multi-drug resistant pathogens
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DOI：
10.1038/s41598-020-64145-7
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发表时间：
2020-04-28
影响因子：
4.6
通讯作者：
Tomas, Maria
中科院分区：
文献类型：
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作者：
Blasco, Lucia;Ambroa, Anton;Tomas, Maria
多药耐药（MDR）病原菌的出现正在危及抗菌药物的价值，而抗菌药物以前改变了医学科学的进程。在这项研究中，我们鉴定了分别存在于噬菌体Ab 1051 Phi和Ab 1052 Phi基因组中的内溶素ElyA 1和ElyA 2（GH 108-PG 3家族）。使用浊度降低试验测试这些内溶素对MDR临床分离株（鲍氏不动杆菌、铜绿假单胞菌和肺炎克雷伯菌）的壁溶活性。测定内溶素、粘菌素以及内溶素和粘菌素的组合的最小抑制浓度（MIC），并且通过时间杀灭曲线确认每种处理的抗微生物活性。内溶素ElyA 1对所有25株A.鲍曼不动杆菌和铜绿假单胞菌对17株K.肺炎。内溶素ElyA 2不显示任何此类活性。粘菌素和ElyA 1的组合抗微生物活性导致所有研究菌株的粘菌素MIC降低，除了K。肺炎。这些结果在G.在小鼠皮肤和肺感染模型中的应用。总之，在体外和体内研究中，将粘菌素（1/4 MIC）与新的内溶素ElyA 1（350 μ g）组合增强了粘菌素的杀菌活性。这将可能减少临床实践中使用的粘菌素剂量。
The emergence of multidrug resistant (MDR) pathogenic bacteria is jeopardizing the value of antimicrobials, which had previously changed the course of medical science. In this study, we identified endolysins ElyA1 and ElyA2 (GH108-PG3 family), present in the genome of bacteriophages Ab1051 Phi and Ab1052 Phi, respectively. The muralytic activity of these endolysins against MDR clinical isolates (Acinetobacter baumannii, Pseudomonas aeruginosa and Klebsiella pneumoniae) was tested using the turbidity reduction assay. Minimal inhibitory concentrations (MICs) of endolysin, colistin and a combination of endolysin and colistin were determined, and the antimicrobial activity of each treatment was confirmed by time kill curves. Endolysin ElyA1 displayed activity against all 25 strains of A. baumannii and P. aeruginosa tested and against 13 out of 17 strains of K. pneumoniae. Endolysin ElyA2 did not display any such activity. The combined antimicrobial activity of colistin and ElyA1 yielded a reduction in the colistin MIC for all strains studied, except K. pneumoniae. These results were confirmed in vivo in G. mellonella survival assays and in murine skin and lung infection models. In conclusion, combining colistin (1/4 MIC) with the new endolysin ElyA1 (350 mu g) enhanced the bactericidal activity of colistin in both in vitro and in vivo studies. This will potentially enable reduction of the dose of colistin used in clinical practice.