Genome-wide screen in human plasma identifies multifaceted complement evasion of Pseudomonas aeruginosa

Autor: Manon Janet-Maitre, Stéphane Pont, Frerich M. Masson, Serena Sleiman, Julian Trouillon, Mylène Robert-Genthon, Benoît Gallet, Chantal Dumestre-Perard, Sylvie Elsen, Christine Moriscot, Bart W. Bardoel, Suzan H. M. Rooijakkers, François Cretin, Ina Attrée
Přispěvatelé: Groupe Pathogenèse Bactérienne et Réponses Cellulaires / Bacterial Pathogenesis and Cellular Responses Group (IBS-PBRC), Institut de biologie structurale (IBS - UMR 5075), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA), Groupe Microscopie Electronique et Méthodes (IBS-MEM), Integrated Structural Biology Grenoble (ISBG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-European Molecular Biology Laboratory [Grenoble] (EMBL)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), University Medical Center [Utrecht], Laboratoire d'Immunologie, CHU Grenoble
Rok vydání: 2023
Předmět:
Zdroj: Plos Pathogens
PLoS Pathogens
PLoS Pathogens, 2023, 1386 (1), pp.325-345. ⟨10.1371/journal.ppat.1011023⟩
PLoS Pathogens, 2023, 19 (1), pp.e1011023. ⟨10.1371/journal.ppat.1011023⟩
ISSN: 1553-7366
1553-7374
DOI: 10.1371/journal.ppat.1011023
Popis: Pseudomonas aeruginosa, an opportunistic Gram-negative pathogen, is a leading cause of bacteremia with a high mortality rate. We recently reported that P. aeruginosa forms a persister-like sub-population of evaders in human plasma. Here, using a gain-of-function transposon sequencing (Tn-seq) screen in plasma, we identified and validated previously unknown factors affecting bacterial persistence in plasma. Among them, we identified a small periplasmic protein, named SrgA, whose expression leads to up to a 100-fold increase in resistance to killing. Additionally, mutants in pur and bio genes displayed higher tolerance and persistence, respectively. Analysis of several steps of the complement cascade and exposure to an outer-membrane-impermeable drug, nisin, suggested that the mutants impede membrane attack complex (MAC) activity per se. Electron microscopy combined with energy-dispersive X-ray spectroscopy (EDX) revealed the formation of polyphosphate (polyP) granules upon incubation in plasma of different size in purD and wild-type strains, implying the bacterial response to a stress signal. Indeed, inactivation of ppk genes encoding polyP-generating enzymes lead to significant elimination of persisting bacteria from plasma. Through this study, we shed light on a complex P. aeruginosa response to the plasma conditions and discovered the multifactorial origin of bacterial resilience to MAC-induced killing.
Databáze: OpenAIRE
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