The great phage escape: Activating and escaping lactococcal antiphage systems

• 成果类型: Article
• 署名作者: Mosterd, Cas; Grafakou, Andriana; Charneco, Guillermo Ortiz; de Waal, Paul P.; van Rijswijck, Irma M. H.; van Peij, Noel N. M. E.; Pechoux, Christine; Kulakauskas, Saulius; Cambillau, Christian; Mahony, Jennifer; van Sinderen, Douwe
• 署名单位: University College Cork; University College Cork; AgroParisTech; INRAE; Universite Paris Saclay; Universite Paris Saclay; INRAE; AgroParisTech; Aix-Marseille Universite; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB)
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-14283
• DOI: 10.1073/pnas.2426508122
• 发表日期: 2025-06-17
• 关键词: abortive infection mechanism; bacteriophage; protein; sensitivity; identification; resistance; DEFENSE; region; genes

摘要

In recent years, the number of newly discovered systems that bacteria use to combat bacteriophages is increasing at an impressive rate. To obtain mechanistic insights into several antiphage systems identified in previous studies, we isolated 66 phage escape mutants which had become insensitive to 13 distinct, plasmid- encoded lactococcal phage mutants identified a total of 15 mutated genes. Six of the encoded proteins appear to activate specific antiphage systems. Furthermore, AbiA escape mutants were found to be insensitive to AbiJ, while distinct antiphage systems (AbiG and AbiP) were observed to be activated by a major phage tail protein, indicating mechanistic commonalities. similar sensing mechanisms, whereas our data indicate mechanistic differences between Septu homologues from different genera. Based on our escape mutant sequence analysis, previously predicted domains, and experimental data using the purified endolysin of phage c2, we propose that Audmula modifies the cell wall of the host bacterium, delaying cell lysis and release of progeny phages, protecting the host cell by a heretofore unknown mode of action. The obtained advances in our understanding of lactococcal antiphage mechanisms provide fundamental insights into phage-host interactions, which undoubtedly benefits the dairy industry but may also be useful for biotechnological or biomedical applications.