Paškevičius Šarūnas, Starkevič Urtė, Misiūnas Audrius, Vitkauskienė Astra, Gleba Yuri, Ražanskienė Aušra
Nomads UAB, Geležinio vilko 29A, Vilnius, Lithuania.
Vilnius University, Institute of Biotechnology, Saulėtekio al. 7, Vilnius, Lithuania.
PLoS One. 2017 Oct 3;12(10):e0185782. doi: 10.1371/journal.pone.0185782. eCollection 2017.
The emergence, persistence and spread of antibiotic-resistant human pathogenic bacteria heralds a growing global health crisis. Drug-resistant strains of gram-negative bacteria, such as Pseudomonas aeruginosa, are especially dangerous and the medical and economic burden they impose underscore the critical need for finding new antimicrobials. Recent studies have demonstrated that plant-expressed bacteriocins of the colicins family can be efficient antibacterials against all major enteropathogenic strains of E. coli. We extended our studies of colicin-like bacteriocins to pyocins, which are produced by strains of P. aeruginosa for ecological advantage against other strains of the same species. Using a plant-based transient expression system, we expressed six different pyocins, namely S5, PaeM, L1, L2, L3 and one new pyocin, PaeM4, and purified them to homogeneity. Among these pyocins, PaeM4 demonstrated the broadest spectrum of activity by controlling 53 of 100 tested clinical isolates of P. aeruginosa. The activity of plant-made pyocins was confirmed in the agar drop, liquid culture susceptibility and biofilm assays, and in the Galleria mellonella animal infection model.
抗生素耐药性人类病原菌的出现、持续存在和传播预示着一场日益严重的全球健康危机。革兰氏阴性菌的耐药菌株,如铜绿假单胞菌,尤其危险,它们所带来的医学和经济负担凸显了寻找新型抗菌药物的迫切需求。最近的研究表明,植物表达的大肠杆菌素家族细菌素可有效对抗所有主要的致病性大肠杆菌菌株。我们将对类大肠杆菌素细菌素的研究扩展到绿脓菌素,绿脓菌素由铜绿假单胞菌菌株产生,用于在生态上对抗同一物种的其他菌株。利用基于植物的瞬时表达系统,我们表达了六种不同的绿脓菌素,即S5、PaeM、L1、L2、L3以及一种新的绿脓菌素PaeM4,并将它们纯化至同质。在这些绿脓菌素中,PaeM4通过控制100株受试铜绿假单胞菌临床分离株中的53株,表现出最广泛的活性谱。植物制造的绿脓菌素的活性在琼脂扩散、液体培养敏感性和生物膜测定以及大蜡螟动物感染模型中得到了证实。