Department of Biochemistry and Genetics, Jan Kochanowski University, Kielce, Poland.
Department of Pathogen Biology and Immunology, Institute of Genetics and Microbiology, University of Wroclaw, Wroclaw, Poland.
Bioorg Chem. 2019 Oct;91:103121. doi: 10.1016/j.bioorg.2019.103121. Epub 2019 Jul 11.
Nowadays, the researchers make a big effort to find new alternatives to overcome bacterial drug resistance. One option is the application of bacteriophage endolysins enable to degrade peptidoglycan (PG) what in consequence leads to bacterial cell lysis. In this study we examine phage KP27 endolysin mixed with poly(propyleneimine) dendrimers to evaluate an antimicrobial effect against Pseudomonas aeruginosa. Polycationic compounds destabilize bacterial outer membrane (OM) helping endolysins to gain access to PG. We found out that not only bacterial lipopolysaccharide (LPS) is the main hindrance for highly charged cationic dendrimers to disrupt OM and make endolysin reaching the target but also the dendrimer surface modification. The reduction of a positive charge and concentration in maltose poly(propyleneimine) dendrimers significantly increased an antibacterial effect of endolysin. The application of recombinant lysins against Gram-negative bacteria is one of the future therapy options, thus OM permeabilizers such as cationic dendrimers may be of high interest to be combined with PG-degrading enzymes.
如今,研究人员正在努力寻找新的替代品来克服细菌的药物耐药性。一种选择是应用噬菌体溶菌素,使细菌肽聚糖(PG)降解,从而导致细菌细胞裂解。在这项研究中,我们研究了噬菌体 KP27 溶菌素与聚(丙稀亚胺)树枝状大分子的混合,以评估其对铜绿假单胞菌的抗菌作用。带正电荷的化合物会破坏细菌外膜(OM),帮助溶菌素进入 PG。我们发现,不仅是细菌脂多糖(LPS),高度带正电荷的阳离子树枝状大分子破坏 OM 并使溶菌素到达靶标,而且还有树枝状大分子的表面修饰。麦芽糖聚(丙稀亚胺)树枝状大分子的正电荷和浓度降低显著增加了溶菌素的抗菌作用。重组溶菌素在革兰氏阴性菌中的应用是未来治疗选择之一,因此,像阳离子树枝状大分子这样的 OM 通透剂可能是与 PG 降解酶结合的高度关注对象。