Besse Alison, Menetrey Quentin, Jean-Pierre Vincent, Huc-Brandt Sylvaine, Aujoulat Fabien, Dupont Chloé, Chiron Raphaël, Armengaud Jean, Jumas-Bilak Estelle, Molle Virginie, Grenga Lucia, Marchandin Hélène
HydroSciences Montpellier, Univ Montpellier, CNRS, IRD, Montpellier, France.
INFINITE-Institute for Translational Research in Inflammation, Univ Lille, INSERM, Lille, France.
Sci Rep. 2025 Jul 2;15(1):23392. doi: 10.1038/s41598-025-06075-w.
The colonization and persistence of Pseudomonas aeruginosa in chronically diseased lungs are driven by various virulence factors. However, pulmonary infections in cystic fibrosis (CF) patients are predominantly polymicrobial. While Achromobacter xylosoxidans is an opportunistic pathogen in these patients, its impact on P. aeruginosa virulence during co-infection remains largely unknown. This study investigated P. aeruginosa interaction with two clonally related A. xylosoxidans strains, Ax 198 and Ax 200, co-isolated from CF sputum. We found that the interaction was strain-dependent, with Ax 200 significantly reducing P. aeruginosa virulence in a zebrafish model, providing the first in vivo evidence of this interaction. Proteomic analysis revealed that P. aeruginosa proteome was differently impacted by the two A. xylosoxidans strains, with Ax 200 altering proteins involved in biofilm formation, swimming motility, iron acquisition, and secretion systems. These findings were validated by phenotypic assays, confirming that A. xylosoxidans affected major P. aeruginosa virulence phenotypes, including biofilm formation, swimming motility, and siderophore production. Genetic analysis confirmed that distinct regulatory mechanisms, including iron cycle pathways, may account for the strain-dependent effects. These findings reveal a novel multi-target competitive mechanism through which A. xylosoxidans significantly disrupts P. aeruginosa virulence.
铜绿假单胞菌在慢性疾病肺部的定殖和持续存在是由多种毒力因子驱动的。然而，囊性纤维化（CF）患者的肺部感染主要是多微生物感染。虽然木糖氧化无色杆菌是这些患者中的一种机会致病菌，但其在共感染期间对铜绿假单胞菌毒力的影响仍 largely unknown。本研究调查了铜绿假单胞菌与从CF痰液中共分离出的两种克隆相关的木糖氧化无色杆菌菌株Ax 198和Ax 200的相互作用。我们发现这种相互作用具有菌株依赖性，Ax 200在斑马鱼模型中显著降低了铜绿假单胞菌的毒力，为这种相互作用提供了首个体内证据。蛋白质组学分析表明，两种木糖氧化无色杆菌菌株对铜绿假单胞菌蛋白质组的影响不同，Ax 200改变了参与生物膜形成、游动性、铁摄取和分泌系统的蛋白质。这些发现通过表型分析得到验证，证实木糖氧化无色杆菌影响了铜绿假单胞菌的主要毒力表型，包括生物膜形成、游动性和铁载体产生。遗传分析证实，包括铁循环途径在内的不同调控机制可能解释了菌株依赖性效应。这些发现揭示了一种新的多靶点竞争机制，通过该机制木糖氧化无色杆菌显著破坏了铜绿假单胞菌的毒力。
