AUTHOR=González-Alsina Alex , Martín-Merinero Héctor , Mateu-Borrás Margalida , Verd María , Doménech-Sánchez Antonio , Goldberg Joanna B. , Rodríguez de Córdoba Santiago , Albertí Sebastián TITLE=Role of factor H-related protein 3 in Pseudomonas aeruginosa bloodstream infections JOURNAL=Frontiers in Immunology VOLUME=15 YEAR=2024 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1449003 DOI=10.3389/fimmu.2024.1449003 ISSN=1664-3224 ABSTRACT=

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. P. aeruginosa 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 P. aeruginosa 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 P. aeruginosa. Conversely, physiological concentrations of FHR-3 have no significant effect. Our findings suggest that FHR-3 may serve as a protective host factor against P. aeruginosa infections.