Department of Biochemistry and Biophysics, Texas A&M University, College Station, TX 77843, USA.
Center for Phage Technology, Texas A&M University, College Station, TX 77843, USA.
Science. 2024 Apr 5;384(6691):eadl0635. doi: 10.1126/science.adl0635.
The retractile type IV pilus (T4P) is important for virulence of the opportunistic human pathogen . The single-stranded RNA (ssRNA) phage PP7 binds to T4P and is brought to the cell surface through pilus retraction. Using fluorescence microscopy, we discovered that PP7 detaches T4P, which impairs cell motility and restricts the pathogen's virulence. Using cryo-electron microscopy, mutagenesis, optical trapping, and Langevin dynamics simulation, we resolved the structure of PP7, T4P, and the PP7/T4P complex and showed that T4P detachment is driven by the affinity between the phage maturation protein and its bound pilin, plus the pilus retraction force and speed, and pilus bending. Pilus detachment may be widespread among other ssRNA phages and their retractile pilus systems and offers new prospects for antibacterial prophylaxis and therapeutics.
回缩型 IV 型菌毛 (T4P) 对机会性病原体的毒力很重要。单链 RNA (ssRNA) 噬菌体 PP7 结合到 T4P 上,并通过菌毛回缩带到细胞表面。通过荧光显微镜,我们发现 PP7 会脱离 T4P,从而损害细胞的运动能力并限制病原体的毒力。通过低温电子显微镜、突变、光镊和朗之万动力学模拟,我们解析了 PP7、T4P 和 PP7/T4P 复合物的结构,并表明 PP7 与结合的菌毛之间的亲和力、菌毛回缩力和速度以及菌毛弯曲驱动了 T4P 的脱离。菌毛脱离可能在其他 ssRNA 噬菌体及其回缩菌毛系统中很普遍,为抗菌预防和治疗提供了新的前景。