Contribution of intramacrophage stages to Pseudomonas aeruginosa infection outcome in zebrafish embryos: insights from mgtC and oprF mutants.

Autor: Hajjar H; Laboratory of Pathogens and Host Immunity (LPHI), Université de Montpellier, CNRS-UMR5294, INSERM, Montpellier, France., Berry L; Laboratory of Pathogens and Host Immunity (LPHI), Université de Montpellier, CNRS-UMR5294, INSERM, Montpellier, France., Wu Y; Institut Pasteur, Université Paris Cité, CNRS UMR3691, Cellular Biology and Microbial Infection Unit, Paris, France., Touqui L; Sorbonne Université, Inserm U938, Centre de Recherche Saint-Antoine (CRSA), Paris, France.; Institut Pasteur, Université de Paris Cité, Mucoviscidose et Bronchopathies Chroniques, Paris, France., Vergunst AC; Bacterial Virulence and Chronic Infections (VBIC), Université de Montpellier, INSERM, U1047, Nîmes, France. annette.vergunst@umontpellier.fr., Blanc-Potard AB; Laboratory of Pathogens and Host Immunity (LPHI), Université de Montpellier, CNRS-UMR5294, INSERM, Montpellier, France. anne.blanc-potard@umontpellier.fr.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2024 Mar 15; Vol. 14 (1), pp. 6297. Date of Electronic Publication: 2024 Mar 15.
DOI: 10.1038/s41598-024-56725-8
Abstrakt: Pseudomonas aeruginosa often colonizes immunocompromised patients, causing acute and chronic infections. This bacterium can reside transiently inside cultured macrophages, but the contribution of the intramacrophic stage during infection remains unclear. MgtC and OprF have been identified as important bacterial factors when P. aeruginosa resides inside cultured macrophages. In this study, we showed that P. aeruginosa mgtC and oprF mutants, particular the latter one, had attenuated virulence in both mouse and zebrafish animal models of acute infection. To further investigate P. aeruginosa pathogenesis in zebrafish at a stage different from acute infection, we monitored bacterial load and visualized fluorescent bacteria in live larvae up to 4 days after infection. Whereas the attenuated phenotype of the oprF mutant was associated with a rapid elimination of bacteria, the mgtC mutant was able to persist at low level, a feature also observed with the wild-type strain in surviving larvae. Interestingly, these persistent bacteria can be visualized in macrophages of zebrafish. In a short-time infection model using a macrophage cell line, electron microscopy revealed that internalized P. aeruginosa wild-type bacteria were either released after macrophage lysis or remained intracellularly, where they were localized in vacuoles or in the cytoplasm. The mgtC mutant could also be detected inside macrophages, but without causing cell damage, whereas the oprF mutant was almost completely eliminated after phagocytosis, or localized in phagolysosomes. Taken together, our results show that the main role of OprF for intramacrophage survival impacts both acute and persistent infection by this bacterium. On the other hand, MgtC plays a clear role in acute infection but is not essential for bacterial persistence, in relation with the finding that the mgtC mutant is not completely eliminated by macrophages.
(© 2024. The Author(s).)
Databáze: MEDLINE
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