Yang Hang, Wang Mengyue, Yu Junping, Wei Hongping
Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases, Wuhan Institute of Virology, Chinese Academy of Sciences Wuhan, China.
Front Microbiol. 2015 Dec 22;6:1471. doi: 10.3389/fmicb.2015.01471. eCollection 2015.
The global emergence of multidrug-resistant (MDR) bacteria is a growing threat to public health worldwide. Natural bacteriophage lysins are promising alternatives in the treatment of infections caused by Gram-positive pathogens, but not Gram-negative ones, like Acinetobacter baumannii and Pseudomonas aeruginosa, due to the barriers posed by their outer membranes. Recently, modifying a natural lysin with an antimicrobial peptide was found able to break the barriers, and to kill Gram-negative pathogens. Herein, a new peptide-modified lysin (PlyA) was constructed by fusing the cecropin A peptide residues 1-8 (KWKLFKKI) with the OBPgp279 lysin and its antibacterial activity was studied. PlyA showed good and broad antibacterial activities against logarithmic phase A. baumannii and P. aeruginosa, but much reduced activities against the cells in stationary phase. Addition of outer membrane permeabilizers (EDTA and citric acid) could enhance the antibacterial activity of PlyA against stationary phase cells. Finally, no antibacterial activity of PlyA could be observed in some bio-matrices, such as culture media, milk, and sera. In conclusion, we reported here a novel peptide-modified lysin with significant antibacterial activity against both logarithmic (without OMPs) and stationary phase (with OMPs) A. baumannii and P. aeruginosa cells in buffer, but further optimization is needed to achieve broad activity in diverse bio-matrices.
多重耐药（MDR）细菌在全球范围内的出现对全球公共卫生构成了日益严重的威胁。天然噬菌体溶菌酶是治疗革兰氏阳性病原体引起的感染的有前景的替代物，但对于革兰氏阴性病原体，如鲍曼不动杆菌和铜绿假单胞菌则无效，因为它们的外膜会造成障碍。最近，发现用抗菌肽修饰天然溶菌酶能够突破这些障碍，并杀死革兰氏阴性病原体。在此，通过将天蚕素A肽的第1 - 8位残基（KWKLFKKI）与OBPgp279溶菌酶融合构建了一种新的肽修饰溶菌酶（PlyA），并研究了其抗菌活性。PlyA对对数生长期的鲍曼不动杆菌和铜绿假单胞菌显示出良好且广泛的抗菌活性，但对稳定期细胞的活性则大大降低。添加外膜通透剂（EDTA和柠檬酸）可以增强PlyA对稳定期细胞的抗菌活性。最后，在一些生物基质中，如培养基、牛奶和血清中未观察到PlyA的抗菌活性。总之，我们在此报道了一种新型的肽修饰溶菌酶，其在缓冲液中对对数期（无外膜蛋白）和稳定期（有外膜蛋白）的鲍曼不动杆菌和铜绿假单胞菌细胞均具有显著的抗菌活性，但需要进一步优化以在多种生物基质中实现广泛的活性。
