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Coxiella burnetii Infection of Host Cells Involves PKC substrate MARCKS
Author(s) -
Whitlock Sara,
Funk Cornelius Joel
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.744.3
Subject(s) - marcks , coxiella burnetii , vacuole , protein kinase c , biology , microbiology and biotechnology , cytoplasm , phosphorylation
The human disease Q‐fever is initiated as a respiratory tract infection by the bacterium Coxiella burnetii . Acute infections typically result in flu‐like symptoms and can be treated with antibiotics, but untreated chronic infections can lead to severe conditions including endocarditis. Bacteria enter alveolar macrophages within a phagosome, but instead of being destroyed by cellular enzymes bacterial cells induce the host cell to develop a lysosome‐like organelle called the parasitophorous vacuole (PV) where replication takes place. The PV starts small but grows in size to accommodate the increasing number of replicating cells. Manipulation of the host infection by C. burnetii includes altering Protein Kinase C (PKC) cell signaling events beginning at early times of the infection. PKC activation is initiated through multiple isoforms that sequentially phosphorylate downstream substrates. MARCKS is one of several PKC substrates phosphorylated during infections. The objective of this study was to localize MARCKS using antibodies and examine the role of MARCKS using specific inhibitors. Our results indicate that MARCKS localizes to the PV membrane and surrounding cytoplasm. The level of MARCKS protein was knocked‐down using siRNA treatment of HeLa cells. Infected cells treated with MARCKS siRNA contained C. burnetii , but many PV's were larger in size and contained fewer bacteria than those of infected cells treated with control siRNA. A peptide inhibitor of MARCKS appeared to have a similar effect on infected THP‐1 cells by causing enlarged PV's compared to control peptide treatments. These results indicate that MARCKS may have a role in regulating or controlling the size of C. burnetii ‐induced PV's through manipulation of the host cell PKC signaling system. Support or Funding Information Supported by a grant from Arkansas INBRE (NIH NIGMS P20 GM103429).