Tobares Romina A, Martino Román A, Colque Claudia A, Castillo Moro Gaston L, Moyano Alejandro J, Albarracín Orio Andrea G, Smania Andrea M
Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Química Biológica "Ranwel Caputto", Córdoba, Argentina.
CONICET. Universidad Nacional de Córdoba. Centro de Investigaciones en Química Biológica de Córdoba (CIQUIBIC), Córdoba, Argentina.
NPJ Biofilms Microbiomes. 2025 Jan 13;11(1):14. doi: 10.1038/s41522-024-00644-z.
Biofilms are critical in the persistence of Pseudomonas aeruginosa infections, particularly in cystic fibrosis patients. This study explores the adaptive mechanisms behind the phenotypic switching between Small Colony Variants (SCVs) and revertant states in P. aeruginosa biofilms, emphasizing hypermutability due to Mismatch Repair System (MRS) deficiencies. Through experimental evolution and whole-genome sequencing, we show that both wild-type and mutator strains undergo parallel evolution by accumulating compensatory mutations in factors regulating intracellular c-di-GMP levels, particularly in the Wsp and Yfi systems. While wild-type strains face genetic constraints, mutator strains bypass these by accessing alternative genetic pathways regulating c-di-GMP and biofilm formation. This increased genetic accessibility, driven by higher mutation rates and specific mutational biases, supports sustained cycles of SCV conversion and reversion. Our findings underscore the crucial role of hypermutability in P. aeruginosa adaptation, with significant implications for managing persistent infections in clinical settings.
生物膜在铜绿假单胞菌感染的持续性中起着关键作用，尤其是在囊性纤维化患者中。本研究探讨了铜绿假单胞菌生物膜中小菌落变体（SCV）与回复态之间表型转换背后的适应性机制，强调了错配修复系统（MRS）缺陷导致的高突变性。通过实验进化和全基因组测序，我们表明野生型菌株和突变菌株通过在调节细胞内c-di-GMP水平的因子中积累补偿性突变而经历平行进化，特别是在Wsp和Yfi系统中。虽然野生型菌株面临遗传限制，但突变菌株通过进入调节c-di-GMP和生物膜形成的替代遗传途径绕过了这些限制。由较高的突变率和特定的突变偏向驱动的这种增加的遗传可及性，支持了SCV转换和回复的持续循环。我们的发现强调了高突变性在铜绿假单胞菌适应中的关键作用，对临床环境中持续性感染的管理具有重要意义。
