Tesson Florian, Huiting Erin, Wei Linlin, Ren Jie, Johnson Matthew, Planel Rémi, Cury Jean, Feng Yue, Bondy-Denomy Joseph, Bernheim Aude
Institut Pasteur, CNRS UMR3525, Molecular Diversity of Microbes Lab, 25-28 rue du Docteur Roux, 75015, Paris, France.
Department of Microbiology and Immunology, University of California San Francisco, Genentech Hall Room N372E UCSF Mail Code 2200 600 16th Street San Francisco, San Francisco, CA 94158, USA.
Nucleic Acids Res. 2025 Jan 7;53(1). doi: 10.1093/nar/gkae1171.
The co-evolution of prokaryotes, phages and mobile genetic elements (MGEs) has driven the diversification of defense and anti-defense systems alike. Anti-defense proteins have diverse functional domains, sequences and are typically small, creating a challenge to detect anti-defense homologs across prokaryotic and phage genomes. To date, no tools comprehensively annotate anti-defense proteins within a desired sequence. Here, we developed 'AntiDefenseFinder'-a free open-source tool and web service that detects 156 anti-defense systems of one or more proteins in any genomic sequence. Using this dataset, we identified 47 981 anti-defense systems distributed across prokaryotes and their viruses. We found that some genes co-localize in 'anti-defense islands', including Escherichia coli T4 and Lambda phages, although many appear standalone. Eighty-nine per cent anti-defense systems localize only or preferentially in MGE. However, >80% of anti-Pycsar protein 1 (Apyc1) resides in nonmobile regions of bacterial genomes. Evolutionary analysis and biochemical experiments revealed that Apyc1 likely originated in bacteria to regulate cyclic nucleotide (cNMP) signaling, but phage co-opted Apyc1 to overcome cNMP-utilizing defenses. With the AntiDefenseFinder tool, we hope to facilitate the identification of the full repertoire of anti-defense systems in MGEs, the discovery of new protein functions and a deeper understanding of host-pathogen arms race.
原核生物、噬菌体和移动遗传元件（MGEs）的共同进化推动了防御系统和反防御系统的多样化。反防御蛋白具有多样的功能结构域、序列，且通常较小，这给在原核生物和噬菌体基因组中检测反防御同源物带来了挑战。迄今为止，尚无工具能全面注释所需序列中的反防御蛋白。在此，我们开发了“反防御蛋白发现者”——一种免费的开源工具和网络服务，可在任何基因组序列中检测一种或多种蛋白的156种反防御系统。利用该数据集，我们在原核生物及其病毒中鉴定出47981个反防御系统。我们发现一些基因共定位于“反防御岛”，包括大肠杆菌T4和λ噬菌体，尽管许多基因看起来是独立存在的。89%的反防御系统仅定位或优先定位在MGE中。然而，超过80%的抗Pycsar蛋白1（Apyc1）位于细菌基因组的非移动区域。进化分析和生化实验表明，Apyc1可能起源于细菌以调节环核苷酸（cNMP）信号传导，但噬菌体采用Apyc1来克服利用cNMP的防御。借助“反防御蛋白发现者”工具，我们希望促进对MGE中反防御系统全部组成的鉴定、新蛋白功能的发现以及对宿主-病原体军备竞赛的更深入理解。
