Department of Microbiology and Immunology, Jacobs School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, New York, USA.
Infect Immun. 2021 Sep 16;89(10):e0017721. doi: 10.1128/IAI.00177-21. Epub 2021 Jul 19.
Proteus mirabilis is a leading uropathogen of catheter-associated urinary tract infections (CAUTIs), which are among the most common health care-associated infections worldwide. A key factor that contributes to P. mirabilis pathogenesis and persistence during CAUTI is the formation of catheter biofilms, which provide increased resistance to antibiotic treatment and host defense mechanisms. Another factor that is important for bacterial persistence during CAUTI is the ability to resist reactive oxygen species (ROS), such as through the action of the catalase enzyme. Potent catalase activity is one of the defining biochemical characteristics of P. mirabilis, and the single catalase () gene in strain HI4320 was recently identified as a candidate fitness factor for UTI, CAUTI, and bacteremia. Here, we show that disruption of results in increased ROS levels, increased sensitivity to peroxide, and decreased biofilm biomass. The biomass defect was due to a decrease in the production of extracellular polymeric substances (EPS) by the mutant and specifically due to reduced carbohydrate content. Importantly, the biofilm defect resulted in decreased antibiotic resistance and a colonization defect during experimental CAUTI. The mutant also exhibited decreased fitness in a bacteremia model, supporting a dual role for catalase in P. mirabilis biofilm development and immune evasion.
奇异变形杆菌是导致与导尿管相关的尿路感染(CAUTIs)的主要病原体之一,而 CAUTIs 是全球最常见的与医疗保健相关的感染之一。导致奇异变形杆菌在 CAUTI 中发病和持续存在的一个关键因素是导管生物膜的形成,这增加了对抗生素治疗和宿主防御机制的抵抗力。另一个在 CAUTI 期间对细菌持续存在很重要的因素是抵抗活性氧(ROS)的能力,例如通过过氧化氢酶酶的作用。强大的过氧化氢酶活性是奇异变形杆菌的定义生化特征之一,最近在 HI4320 菌株中鉴定出单个过氧化氢酶()基因是尿路感染、CAUTI 和菌血症的候选适应度因子。在这里,我们表明 基因的破坏会导致 ROS 水平升高、对过氧化物的敏感性增加以及生物膜生物量减少。生物量缺陷是由于 突变体产生的细胞外聚合物质(EPS)减少,特别是由于碳水化合物含量减少。重要的是,生物膜缺陷导致抗生素耐药性降低和实验性 CAUTI 期间的定植缺陷。该 突变体在菌血症模型中也表现出适应性降低,这支持了过氧化氢酶在奇异变形杆菌生物膜发育和免疫逃避中的双重作用。