3 years ago

Sensing Mg2+ contributes to the resistance of Pseudomonas aeruginosa to complement-mediated opsonophagocytosis

Antonio Doménech-Sánchez, Sofía Izquierdo-Rabassa, Joanna B. Goldberg, Carlos Juan, Mohammad Qadi, Sebastián Albertí, Robert E.W. Hancock, Margalida Mateu Borrás
Pseudomonas aeruginosa adaptation to survive in the host hinges on its ability to probe the environment and respond appropriately. Rapid adaptation is often mediated by two-component regulatory systems, such as the PhoP/PhoQ system that responds to Mg2+ ion concentration. However, there is limited information about the role of PhoQ in P. aeruginosa bloodstream infections. We used a murine model of systemic infection to test the virulence of a PhoQ-deficient mutant. Mutation of PhoQ impaired the virulence and the ability to cause bacteremia of P. aeruginosa. In the presence of blood concentrations of Mg2+, a PhoQ mutant bound more C3 and was more susceptible to complement-mediated opsonophagocytosis than the parent strain, suggesting a direct effect of the Mg2+ on the modulation of expression of a bacterial component controlled by the PhoP/PhoQ system. Ligand blot analysis, C3 binding experiments and opsonophagocytosis assays identified this component as the outer membrane protein OprH, expression of which impaired the virulence of P. aeruginosa in a murine model of systemic infection. We demonstrate that expression of PhoQ is essential to detect Mg2+ and reduce the expression of OprH, a previously unrecognized C3 binding molecule that promotes the opsonophagocytosis of P. aeruginosa. This article is protected by copyright. All rights reserved.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1111/1462-2920.13889

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