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高耐药性囊性纤维化来源菌株中噬菌体抗性进化与抗生素敏感性之间的权衡

Tradeoffs Between Evolved Phage Resistance and Antibiotic Susceptibility in a Highly Drug-Resistant Cystic Fibrosis-Derived Strain.

作者信息

Wilburn Kaylee, Matrishin Cole B, Choudhury Anika, Larsen Ray, Wildschutte Hans

机构信息

Department of Biological Sciences, Bowling Green State University, Bowling Green, Ohio, USA.

Department of Oral Biology, University at Buffalo, Buffalo, New York, USA.

出版信息

Phage (New Rochelle). 2024 Jun 21;5(2):45-52. doi: 10.1089/phage.2023.0022. eCollection 2024 Jun.

Abstract

BACKGROUND

Multi-drug resistant pathogens pose significant challenges towards the effective resolution of bacterial infections. A promising alternative strategy is phage therapy in which limited applications has afforded lifesaving resolution from drug resistant pathogens. However, adoption of this strategy is hampered by narrow bacteriophage host ranges, and as with antibiotics, bacteria can acquire resistance to phage.

METHODS

To address these issues, we isolated 25 broad-host range phages against multiple cystic fibrosis (CF)-derived clinical strains thus promoting their application against conspecific pathogens. To investigate evolved resistance to phage in relation to antibiotic resistance, one CF-derived strain was exposed to a lytic phage over a short time scale.

RESULTS

Trade-offs were observed in which evolved phage resistant strains showed decreased resistance to antibiotics. These traits that likely reflect single nucleotide polymorphisms.

CONCLUSION

Results suggest phage and antibiotics may be a combined approach to treat bacterial infections.

摘要

背景

多重耐药病原体对有效解决细菌感染构成重大挑战。一种有前景的替代策略是噬菌体疗法,其有限的应用已为耐药病原体感染提供了挽救生命的治疗效果。然而,该策略的应用受到噬菌体宿主范围狭窄的阻碍,并且与抗生素一样,细菌可获得对噬菌体的抗性。

方法

为解决这些问题,我们分离出25种针对多种源自囊性纤维化(CF)的临床菌株的广宿主范围噬菌体,从而促进其针对同种病原体的应用。为研究与抗生素抗性相关的噬菌体抗性进化,在短时间内将一种源自CF的菌株暴露于一种裂解性噬菌体。

结果

观察到权衡取舍,即进化出噬菌体抗性的菌株对抗生素的抗性降低。这些性状可能反映了单核苷酸多态性。

结论

结果表明噬菌体和抗生素可能是治疗细菌感染的联合方法。

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