Muharram Magdy Mohamed, Abulhamd Ashraf Tawfik, Aldawsari Mohammed F, Alqarni Mohamed Hamed, Labrou Nikolaos E
Department of Pharmaceutics, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Alkharj 11942, Saudi Arabia.
Department of Microbiology, College of Science, Al-Azhar University, Cairo 11884, Egypt.
Antibiotics (Basel). 2020 Mar 30;9(4):148. doi: 10.3390/antibiotics9040148.
Given the worldwide increase in antibiotic resistant bacteria, bacteriophage derived endolysins represent a very promising new alternative class of antibacterials in the fight against infectious diseases. Endolysins are able to degrade the prokaryotic cell wall, and therefore have potential to be exploited for biotechnological and medical purposes. is a Gram-positive multidrug-resistant (MDR) bacterium of human skin. It is a health concern as it is involved in nosocomial infections. Genome-based screening approach of the complete genome of virus PH15 allowed the identification of an endolysin gene (Ph28; NCBI accession number: YP_950690). Bioinformatics analysis of the Ph28 protein predicted that it is a two-domain enzyme composed by a CHAP (22-112) and MurNAc-LAA (171-349) domain. Phylogenetic analysis and molecular modelling studies revealed the structural and evolutionary features of both domains. The MurNAc-LAA domain was cloned, and expressed in BL21 (DE3). In turbidity reduction assays, the recombinant enzyme can lyse more efficiently untreated cells, compared to other strains, suggesting enhanced specificity for . These results suggest that the MurNAc-LAA domain from Ph28 endolysin may represent a promising new enzybiotic.
鉴于全球抗生素耐药菌的增加，噬菌体来源的内溶素在对抗传染病方面代表了一类非常有前景的新型抗菌剂。内溶素能够降解原核细胞壁，因此有潜力用于生物技术和医学目的。[具体细菌名称]是一种人类皮肤的革兰氏阳性多重耐药（MDR）细菌。由于它与医院感染有关，因此是一个健康问题。基于基因组的对[具体病毒名称]病毒PH15完整基因组的筛选方法，使得一个内溶素基因（Ph28；NCBI登录号：YP_950690）得以鉴定。对Ph28蛋白的生物信息学分析预测它是一种双结构域酶，由一个CHAP（22 - 112）和MurNAc - LAA（171 - 349）结构域组成。系统发育分析和分子建模研究揭示了这两个结构域的结构和进化特征。MurNAc - LAA结构域被克隆，并在[具体表达宿主菌名称]BL21（DE3）中表达。在浊度降低试验中，与其他[具体细菌名称]菌株相比，重组酶能够更有效地裂解未处理的[具体细菌名称]细胞，表明对[具体细菌名称]具有增强的特异性。这些结果表明，来自Ph28内溶素的MurNAc - LAA结构域可能代表一种有前景的新型酶抗菌剂。
