关键词: Pseudomonas aeruginosa antibiotic resistance extensively drug resistant eye drops jumbo phage

Mesh : Humans Bacteriophages / genetics Pseudomonas Infections / microbiology Anti-Bacterial Agents / pharmacology therapeutic use Plasmids Pseudomonas aeruginosa Pseudomonas Phages / genetics

来  源:   DOI:10.1128/aac.00654-23   PDF(Pubmed)

Abstract:
Antibiotic-resistant bacteria present an emerging challenge to human health. Their prevalence has been increasing across the globe due in part to the liberal use of antibiotics that has pressured them to develop resistance. Those bacteria that acquire mobile genetic elements are especially concerning because those plasmids may be shared readily with other microbes that can then also become antibiotic resistant. Serious infections have recently been related to the contamination of preservative-free eyedrops with extensively drug-resistant (XDR) isolates of Pseudomonas aeruginosa, already resulting in three deaths. These drug-resistant isolates cannot be managed with most conventional antibiotics. We sought to identify alternatives to conventional antibiotics for the lysis of these XDR isolates and identified multiple bacteriophages (viruses that attack bacteria) that killed them efficiently. We found both jumbo phages (>200 kb in genome size) and non-jumbo phages that were active against these isolates, the former killing more efficiently. Jumbo phages effectively killed the three separate XDR P. aeruginosa isolates both on solid and liquid medium. Given the ongoing nature of the XDR P. aeruginosa eyedrop outbreak, the identification of phages active against them provides physicians with several novel potential alternatives for treatment.
摘要:
抗生素抗性细菌对人类健康提出了新的挑战。它们的患病率在全球范围内一直在增加,部分原因是抗生素的自由使用迫使它们产生耐药性。那些获得可移动遗传元件的细菌尤其令人担忧,因为这些质粒可能很容易与其他微生物共享,这些微生物也可能产生抗生素抗性。最近,严重感染与不含防腐剂的滴眼液被铜绿假单胞菌的广泛耐药(XDR)分离株污染有关,已经导致三人死亡。这些耐药分离株不能用大多数常规抗生素来管理。我们试图确定用于裂解这些XDR分离物的常规抗生素的替代品,并确定了有效杀死它们的多种噬菌体(攻击细菌的病毒)。我们发现了对这些分离株有活性的巨型噬菌体(基因组大小>200kb)和非巨型噬菌体,前者杀人更有效。巨型噬菌体在固体和液体培养基上有效地杀死了三种单独的XDR铜绿假单胞菌分离株。鉴于XDR铜绿假单胞菌滴眼液爆发的持续性质,对它们有活性的噬菌体的鉴定为医生提供了几种新的潜在治疗方法。
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