Center for Microbial Pathogenesis, Research Institute at Nationwide Children's Hospital, Columbus, Ohio, United States of America.
Department of Microbial Infection and Immunity, The Ohio State University, Columbus, Ohio, United States of America.
PLoS Pathog. 2021 Jan 19;17(1):e1009209. doi: 10.1371/journal.ppat.1009209. eCollection 2021 Jan.
Salmonella Typhi is the primary causative agent of typhoid fever; an acute systemic infection that leads to chronic carriage in 3-5% of individuals. Chronic carriers are asymptomatic, difficult to treat and serve as reservoirs for typhoid outbreaks. Understanding the factors that contribute to chronic carriage is key to development of novel therapies to effectively resolve typhoid fever. Herein, although we observed no distinct clustering of chronic carriage isolates via phylogenetic analysis, we demonstrated that chronic isolates were phenotypically distinct from acute infection isolates. Chronic carriage isolates formed significantly thicker biofilms with greater biomass that correlated with significantly higher relative levels of extracellular DNA (eDNA) and DNABII proteins than biofilms formed by acute infection isolates. Importantly, extracellular DNABII proteins include integration host factor (IHF) and histone-like protein (HU) that are critical to the structural integrity of bacterial biofilms. In this study, we demonstrated that the biofilm formed by a chronic carriage isolate in vitro, was susceptible to disruption by a specific antibody against DNABII proteins, a successful first step in the development of a therapeutic to resolve chronic carriage.
伤寒沙门氏菌是伤寒的主要病原体；这是一种全身性的急性感染，导致 3-5%的个体成为慢性携带者。慢性携带者无症状，难以治疗，是伤寒爆发的传染源。了解导致慢性携带的因素是开发新型疗法以有效治疗伤寒的关键。虽然在此研究中，我们通过系统发生分析并未观察到慢性携带分离株的明显聚类，但我们证明慢性分离株在表型上与急性感染分离株不同。慢性携带分离株形成的生物膜更厚，生物量更大，与急性感染分离株形成的生物膜相比，其细胞外 DNA（eDNA）和 DNABII 蛋白的相对水平明显更高。重要的是，细胞外 DNABII 蛋白包括整合宿主因子（IHF）和组蛋白样蛋白（HU），它们对细菌生物膜的结构完整性至关重要。在这项研究中，我们证明了体外慢性携带分离株形成的生物膜易受针对 DNABII 蛋白的特异性抗体的破坏，这是开发治疗慢性携带的方法的成功的第一步。
