López-Pérez Júlia, Cortés Pilar, Campoy Susana, Erill Ivan, Llagostera Montserrat
Molecular Microbiology Group, Departament de Genètica i de Microbiologia, Universitat Autònoma de Barcelona, 08193 Cerdanyola del Vallès, Barcelona, Spain.
Departament d'Enginyeria de la Informació i de les Comunicacions Àrea de Ciències de la Computació i Intel·ligència Artificial, Universitat Autònoma de Barcelona, 08193 Cerdanyola del Vallès, Barcelona, Spain.
Int J Mol Sci. 2025 May 20;26(10):4918. doi: 10.3390/ijms26104918.
The study of bacterial defense mechanisms against phages is becoming increasingly relevant due to their impact on the effectiveness of phage therapy. Employing a multifaceted approach that combines bioinformatics, molecular microbiology, TEM microscopy, and conventional microbiology techniques, here, we identify the gene as a novel defense factor targeting the virulent phage UAB_Phi20, acquired by Typhimurium through lateral transfer on the IncI1α conjugative plasmid pUA1135 after oral phage therapy in broilers. IbfA, a two-domain protein containing ATPase and TOPRIM domains, significantly reduces UAB_Phi20 productivity, as indicated by decreased EOP, ECOI, and a diminished burst size, potentially reducing cellular viability without causing observable lysis. Our results indicate that IbfA enhances the transcription of early genes, including the antirepressor , which inhibits the C2 repressor of the lytic cycle. This may cause an imbalance in Cro/C2 concentration, leading to the observed reduction in the transcription of late genes encoding structural and cellular lysis proteins, and resulting in the abortion of UAB_Phi20 infection.
由于细菌防御噬菌体的机制对噬菌体疗法的有效性有影响，因此对其的研究变得越来越重要。在这里，我们采用了一种多方面的方法，结合了生物信息学、分子微生物学、透射电子显微镜和传统微生物学技术，确定该基因是一种针对烈性噬菌体UAB_Phi20的新型防御因子，它是鼠伤寒沙门氏菌在肉鸡口服噬菌体治疗后通过侧向转移在IncI1α接合质粒pUA1135上获得的。IbfA是一种含有ATPase和TOPRIM结构域的双结构域蛋白，如EOP、ECOI降低和爆发大小减小所示，它显著降低了UAB_Phi20的生产力，可能在不引起明显裂解的情况下降低细胞活力。我们的结果表明，IbfA增强了早期基因的转录，包括抗阻遏物，它抑制裂解周期的C2阻遏物。这可能导致Cro/C2浓度失衡，导致观察到的编码结构和细胞裂解蛋白的晚期基因转录减少，从而导致UAB_Phi20感染流产。
