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重组 R2-噬菌体能有效治疗感染性创面。

Recombinant R2-pyocin cream is effective in treating infected wounds.

机构信息

Department of Biological Sciences, Texas Tech University, Lubbock, TX, USA.

Department of Surgery, Texas Tech University Health Sciences Center, Lubbock, TX, USA.

出版信息

Can J Microbiol. 2021 Dec;67(12):919-932. doi: 10.1139/cjm-2021-0207. Epub 2021 Aug 26.

Abstract

, a gram-negative opportunistic pathogen, is one of the major species isolated from infected chronic wounds. The multidrug resistance exhibited by and its ability to form biofilms that are difficult to eradicate, along with the rising cost of producing new antibiotics, has necessitated the search for alternatives to standard antibiotics. Pyocins are antimicrobial compounds produced by that protect themselves from their competitors. We synthesized and purified recombinant R2 pyocin and used it in an aqueous solution (rR2P) or formulated in polyethylene glycol (rR2PC) to treat infected wounds. Clinical strains of were found to be sensitive (completely), partially sensitive, or resistant to rR2P. In the in vitro biofilm model, rR2P inhibited biofilm development by rR2P-sensitive isolates, while rR2PC eliminated partial biofilms formed by these strains in an in vitro wound biofilm model. In the murine model of excision wounds, and at 24 h post-infection, rR2PC application significantly reduced the bioburden of the clinical isolate BPI86. Application of rR2PC containing two glycoside hydrolase antibiofilm agents eliminated BPI86 from infected wounds. These results suggest that the topical application of rR2PC is an effective therapy for treating wounds infected with R2P-senstive strains.

摘要

铜绿假单胞菌是一种革兰氏阴性机会致病菌,是从感染性慢性创面中分离出来的主要菌种之一。铜绿假单胞菌表现出的多药耐药性,以及其形成的生物膜难以消除的特性,再加上生产新抗生素的成本不断上升,这使得人们有必要寻找替代标准抗生素的方法。噬菌体是由铜绿假单胞菌产生的抗菌化合物,可以保护自己免受竞争对手的侵害。我们合成并纯化了重组铜绿假单胞菌 R2 噬菌体,并将其用于水溶液(rR2P)或聚乙二醇(rR2PC)配方中,以治疗感染性伤口。临床分离株被发现对 rR2P 敏感(完全敏感)、部分敏感或耐药。在体外生物膜模型中,rR2P 抑制了 rR2P 敏感分离株的生物膜发育,而 rR2PC 则消除了这些菌株在体外创面生物膜模型中形成的部分生物膜。在切除伤口的小鼠模型中,感染后 24 小时,rR2PC 的应用显著降低了临床分离株 BPI86 的生物负荷。含有两种糖苷水解酶抗生物膜剂的 rR2PC 的应用将 BPI86 从感染性伤口中消除。这些结果表明,rR2PC 的局部应用是治疗 R2P 敏感铜绿假单胞菌感染伤口的有效疗法。

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