0434495 - ÚMG 2015 RIV US eng J - Journal Article
Hartlová, A. - Link, M. - Balounová, Jana - Benešová, Martina - Resch, U. - Strašková, A. - Sobol, Margaryta - Filimonenko, Anatolij - Hozák, Pavel - Krocová, Z. - Gekara, N. - Filipp, Dominik - Stulík, J.
Quantitative Proteomics Analysis of Macrophage-Derived Lipid Rafts Reveals Induction of Autophagy Pathway at the Early Time of Francisella tularensis LVS Infection.
Journal of Proteome Research. Roč. 13, č. 2 (2014), s. 796-804. ISSN 1535-3893. E-ISSN 1535-3907
R&D Projects: GA MO(CZ) OVUOFVZ200808
Institutional support: RVO:68378050
Keywords : innate immune response * bacterial infection * lipid rafts * Francisella tularensis * phagocytosis * autophagy
Subject RIV: EB - Genetics ; Molecular Biology
Impact factor: 4.245, year: 2014 ; AIS: 1.288, rok: 2014
DOI: https://doi.org/10.1021/pr4008656

Francisella tularensis is a highly infectious intracellular pathogen that has evolved an efficient strategy to subvert host defense response to survive inside the host. The molecular mechanisms regulating these host-pathogen interactions and especially those that are initiated at the time of the bacterial entry via its attachment to the host plasma membrane likely predetermine the intracellular fate of pathogen. Here, we provide the evidence that infection of macrophages with F. tularensis leads to changes in protein composition of macrophage-derived lipid rafts, isolated as detergent-resistant membranes (DRMs). Using SILAC-based quantitative proteomic approach, we observed the accumulation of autophagic adaptor protein p62 at the early, stages of microbe-host cell interaction. We confirmed the colocalization of the p62 with ubiquitinated and LC3-decorated intracellular F. tularensis microbes with its maximum at 1 h postinfection. Furthermore, the infection of p62-knockdown host cells led to the transient increase in the intracellular number of microbes up to 4 h after in vitro infection. Together, these data suggest that the activation of the autophagy pathway in F. tularensis infected macrophages, which impacts the early phase of microbial proliferation, is subsequently circumvented by ongoing infection.
Permanent Link: http://hdl.handle.net/11104/0238541