WS11.03Infectious dynamics of bacteriophages that lyse diverse cystic fibrosis Stenotrophomonas maltophilia isolates

IF 5.4 2区医学 Q1 RESPIRATORY SYSTEM

Journal of Cystic Fibrosis Pub Date : 2025-06-01 DOI:10.1016/j.jcf.2025.03.554

C. Crisan , D. Van Tyne , J. Goldberg

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引用次数: 0

Abstract

Objectives

Bacterial pulmonary infections are an important health burden for people with cystic fibrosis (pwCF), even for those taking the CFTR modulator, elexacaftor/tezacaftor/ivacaftor (ETI). Stenotrophomonas maltophilia complex (Smc) is a bacterial pathogen that infects ∼5-30% of pwCF. Infections can lead to increased mortality, more frequent pulmonary exacerbations, and a higher probability of hospitalization. Isolates are often multidrug-resistant, and infections persist even after ETI treatment. Therefore, alternative therapies for Smc are urgently needed. Bacteriophages (phages) are viruses that infect bacteria but do not affect human cells. Lytic phages are efficient at killing specific bacteria (generally from a single species or genus) but leave the healthy microbiome unharmed. Phage therapy uses lytic phages to eradicate bacterial infections and has been successfully administered to pwCF. Smc CF isolates are genomically diverse, and this diversity could impact the ability of phages to target multiple strains. Few phages that lyse CF Smc isolates have been described.

Methods

We isolated lytic Smc phages from soil (Lsmp1) and from wastewater (STM02, STM03, STM04, STM05, and STM06). We performed infection assays to determine the host range of these phages on 25 genomically diverse Smc isolates (12 from pwCF). We also analyzed the genomes of the phages we isolated.

Results

We observed that Lsmp1 and STM06 are specialists, and each only lyse a single, but distinct Smc strain. By contrast, STM02, STM03, STM04, and STM05 are generalists and lyse multiple genetically distinct strains. Lsmp1 has a genome of ∼42 kilobases and is distantly related to the other five phages we studied, which all have genomes of ∼60-61 kilobases.

Conclusions

In this study, we identified both specialist and generalist phages that infect diverse Smc isolates. These results could lead to the development of novel therapies for pwCF infected by multidrug-resistant Smc strains.

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裂解多种囊性纤维化嗜麦芽寡养单胞菌分离株噬菌体的感染动力学

细菌性肺部感染是囊性纤维化（pwCF）患者的重要健康负担，即使对于服用CFTR调节剂、elexaftor /tezacaftor/ivacaftor （ETI）的患者也是如此。嗜麦芽寡养单胞菌复合体（Smc）是一种细菌病原体，感染约5-30%的pwCF。感染可导致死亡率增加，更频繁的肺部恶化，住院的可能性更高。分离株通常具有多重耐药性，即使在ETI治疗后感染仍然存在。因此，迫切需要替代治疗Smc的方法。噬菌体是感染细菌但不影响人体细胞的病毒。裂解噬菌体能够有效地杀死特定的细菌（通常来自单一的物种或属），但不会伤害健康的微生物群。噬菌体疗法使用溶解噬菌体来根除细菌感染，并已成功地用于pwCF。Smc CF分离物具有基因组多样性，这种多样性可能影响噬菌体靶向多种菌株的能力。很少有噬菌体可以分解CF - Smc分离物。方法分别从土壤（Lsmp1）和废水（STM02、STM03、STM04、STM05和STM06）中分离出可溶性Smc噬菌体。我们对25个基因组不同的Smc分离株（12个来自pwCF）进行了感染试验，以确定这些噬菌体的宿主范围。我们还分析了我们分离的噬菌体的基因组。结果我们观察到Lsmp1和STM06是专门的，它们各自只裂解一种不同的Smc菌株。相比之下，STM02、STM03、STM04和STM05是通才，能够裂解多个遗传上不同的菌株。Lsmp1具有约42千碱基的基因组，与我们研究的其他五种噬菌体有远亲关系，它们都具有约60-61千碱基的基因组。结论在本研究中，我们发现了感染多种Smc分离株的专门型和通才型噬菌体。这些结果可能导致开发新的治疗方法，用于耐多药Smc菌株感染的pwCF。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Cystic Fibrosis 医学-呼吸系统

CiteScore

10.10

自引率

13.50%

发文量

1361

审稿时长

50 days

期刊介绍： The Journal of Cystic Fibrosis is the official journal of the European Cystic Fibrosis Society. The journal is devoted to promoting the research and treatment of cystic fibrosis. To this end the journal publishes original scientific articles, editorials, case reports, short communications and other information relevant to cystic fibrosis. The journal also publishes news and articles concerning the activities and policies of the ECFS as well as those of other societies related the ECFS.