Instituto Universitario de Investigación en Ciencias de la Salud (IUNICS), Universidad de las Islas Baleares and Instituto de Investigación Sanitaria de les Illes Balears (IDISBA), Palma de Mallorca, Spain.
Center for Biological Research-Margarita Salas and Centro de Investigación Biomédica En Red (CIBER) de Enfermedades Raras, Madrid, Spain.
Front Immunol. 2024 Sep 4;15:1449003. doi: 10.3389/fimmu.2024.1449003. eCollection 2024.
Pseudomonas aeruginosa is a leading cause of nosocomial bloodstream infections. The outcome of these infections depends on the virulence of the microorganism as well as host-related conditions and factors. The complement system plays a crucial role in defense against bloodstream infections. counteracts complement attack by recruiting Factor H (FH) that inhibits complement amplification on the bacterial surface. Factor H-related proteins (FHRs) are a group of plasma proteins evolutionarily related to FH that have been postulated to interfere this bacterial evasion mechanism. In this study, we demonstrate that FHR-3 competes with purified FH for binding to and identify EF-Tu as a common bacterial target for both complement regulator factors. Importantly, elevated levels of FHR-3 in human serum promote complement activation, leading to increased opsonization and killing of . Conversely, physiological concentrations of FHR-3 have no significant effect. Our findings suggest that FHR-3 may serve as a protective host factor against infections.
铜绿假单胞菌是医院获得性血流感染的主要致病菌。这些感染的结果取决于微生物的毒力以及宿主相关的条件和因素。补体系统在抵御血流感染中起着至关重要的作用。通过招募因子 H (FH)来中和补体攻击,从而抑制细菌表面的补体放大。因子 H 相关蛋白 (FHRs) 是一组与 FH 具有进化关系的血浆蛋白,据推测它们可以干扰这种细菌逃避机制。在这项研究中,我们证明 FHR-3 与 竞争结合,并确定 EF-Tu 是这两种补体调节因子的共同细菌靶标。重要的是,人血清中 FHR-3 水平的升高可促进补体激活,导致 被更多地调理和杀伤。相反,生理浓度的 FHR-3 没有显著影响。我们的研究结果表明,FHR-3 可能作为一种保护性宿主因子,对抗 感染。