Pseudomonas aeruginosa keratitis in mice: effects of topical bacteriophage KPP12 administration.

Pseudomonas aeruginosa keratitis in mice: effects of topical bacteriophage KPP12 administration.
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小鼠铜绿假单胞菌角膜炎:局部噬菌体KPP12给药的影响。

DOI:
10.1371/journal.pone.0047742
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Fukushima A
Fukushima A
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Fukuda K;Ishida W;Uchiyama J;Rashel M;Kato S;Morita T;Muraoka A;Sumi T;Matsuzaki S;Daibata M;Fukushima A

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研究了噬菌体KPP 12对小鼠绿脓杆菌角膜炎的治疗作用。形态学分析表明噬菌体KPP 12是肌尾病毒科的成员,形态型A1,DNA序列分析表明噬菌体KPP 12与PB1样病毒相似。对噬菌体KPP 12基因组的分析没有鉴定出任何与耐药性、致病性或溶原性相关的基因,因此噬菌体KPP 12可能是治疗性的良好候选者。KPP 12显示了从临床眼科感染中分离的铜绿假单胞菌菌株的广泛宿主范围。用铜绿假单胞菌接种划破的角膜导致严重的角膜炎和最终的角膜穿孔。随后单剂量给予KPP 12滴眼液显著改善了疾病结局,并保持了受感染角膜的结构完整性和透明度。KPP12治疗导致中性粒细胞浸润的抑制和感染角膜中细菌清除的极大增强。这些结果表明,噬菌体滴眼液可能是一种新的预防或替代治疗药物,用于治疗继发于耐药菌的感染性角膜炎。
The therapeutic effects of bacteriophage (phage) KPP12 in Pseudomonas aeruginosa keratitis were investigated in mice. Morphological analysis showed that phage KPP12 is a member of the family Myoviridae, morphotype A1, and DNA sequence analysis revealed that phage KPP12 is similar to PB1-like viruses. Analysis of the phage KPP12 genome did not identify any genes related to drug resistance, pathogenicity or lysogenicity, and so phage KPP12 may be a good candidate for therapeutic. KPP12 showed a broad host range for P. aeruginosa strains isolated from clinical ophthalmic infections. Inoculation of the scarified cornea with P. aeruginosa caused severe keratitis and eventual corneal perforation. Subsequent single-dose administration of KPP12 eye-drops significantly improved disease outcome, and preserved the structural integrity and transparency of the infected cornea. KPP12 treatment resulted in the suppression of neutrophil infiltration and greatly enhanced bacterial clearance in the infected cornea. These results indicate that bacteriophage eye-drops may be a novel adjunctive or alternative therapeutic agent for the treatment of infectious keratitis secondary to antibiotic-resistant bacteria.
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