Piché Laurie C, Bories Sophie, Liato Viacheslav, Paquet Valérie E, Saucier Linda, Létourneau-Montminy Marie-Pierre, Charette Steve J, Dubar Rodrigue, Labrie Simon J, Lagüe Patrick, Vincent Antony T
Institut de biologie intégrative et des systèmes (IBIS), Université Laval, Quebec City, QC, G1V 0A6, Canada.
Département des sciences animales, Faculté des sciences de l'agriculture et de l'alimentation, Université Laval, Pavillon Paul-Comtois, 2425 Rue de L'Agriculture, Quebec City, QC, G1V 0A6, Canada.
BMC Genomics. 2025 May 6;26(1):448. doi: 10.1186/s12864-025-11605-x.
Antibiotic resistance is a major issue affecting all spheres of human activity, including agriculture. One significant example is the Avian Pathogenic Escherichia coli (APEC), a bacterium that infects poultry and leads to substantial economic losses in the farming industry. As antibiotics lose efficacity, bacteriophages (phages) -viruses that specifically target bacteria-are emerging as a promising alternative to antibiotics for treating and preventing bacterial infections. However, bacteria can develop resistance to phages through various mechanisms. Studying the coevolution between a phage and its host bacterium is important to gain insight into the phage's potential as a therapeutic agent. This study investigates the evolutionary responses of an APEC strain and a laboratory E. coli strain to a commercial phage originally isolated from APEC.
In most cases, phage resistance resulted in a significant increase in mucoidy. Genomic analysis revealed that this resistance consistently correlated with amino acid changes, particularly in proteins involved in colanic acid production, such as YrfF. Further investigation of a mutation found in the YrfF protein demonstrated that this mutation altered the protein's structure and its interaction with the membrane. Transcriptomic analysis confirmed that the genes involved in colanic acid production were significantly overexpressed. Although the strains possessed a CRISPR-Cas system, it did not contribute to phage resistance.
This study suggests that specific amino acid changes in key proteins may be a mechanism employed by E. coli, including APEC, to defend against phage infections.
抗生素耐药性是影响人类活动各个领域（包括农业）的一个主要问题。一个显著的例子是禽致病性大肠杆菌（APEC），这种细菌感染家禽并给养殖业带来巨大经济损失。随着抗生素效力的丧失，噬菌体（专门靶向细菌的病毒）作为治疗和预防细菌感染的抗生素的一种有前景的替代品正在兴起。然而，细菌可以通过各种机制对噬菌体产生耐药性。研究噬菌体与其宿主细菌之间的共同进化对于深入了解噬菌体作为治疗剂的潜力很重要。本研究调查了一种APEC菌株和一种实验室大肠杆菌菌株对最初从APEC分离的商业噬菌体的进化反应。
在大多数情况下，噬菌体抗性导致黏液样性显著增加。基因组分析表明，这种抗性始终与氨基酸变化相关，特别是在参与产生结肠酸的蛋白质中，如YrfF。对YrfF蛋白中发现的一个突变的进一步研究表明，该突变改变了蛋白质的结构及其与膜的相互作用。转录组分析证实，参与结肠酸产生的基因显著过表达。尽管这些菌株拥有CRISPR-Cas系统，但它对噬菌体抗性没有贡献。
本研究表明，关键蛋白质中的特定氨基酸变化可能是大肠杆菌（包括APEC）抵御噬菌体感染所采用的一种机制。
