<i>Legionella
pneumophila,</i> the etiological
agent of Legionnaires’ disease, replicates intracellularly in protozoan and
human hosts. Successful colonization and replication of this pathogen in host
cells requires the Dot/Icm type IVB secretion system, which translocates over 330
effector proteins into the host cell to modulate various cellular processes. In
this study, we identified RavK (Lpg0969) as a Dot/Icm substrate that targets
the host cytoskeleton and reduces actin filament abundance in mammalian cells
upon ectopic expression. RavK harbors an H<sub>95</sub>E<sub>XX</sub>H<sub>99</sub> (x, any amino acid)
motif associated with diverse metalloproteases, which is essential for the
inhibition of yeast growth and for the induction of cell rounding in HEK293T
cells. We demonstrate that the actin is the cellular target of RavK and that
this effector cleaves actin at a site between residues Thr351 and Phe352. Importantly,
RavK-mediated actin cleavage occurs during <i>L.
pneumophila </i>infection. Cleavage by RavK abolishes the ability of actin to
form polymers. Furthermore, an F352A mutation renders actin resistant to
RavK-mediated cleavage; expression of the mutant in mammalian cells suppresses
the cell rounding phenotype caused by RavK, further establishing that actin is
the physiological substrate of RavK. Thus, <i>L. pneumophila</i> exploits
components of the host cytoskeleton by multiple effectors with distinct
mechanisms, highlighting the importance of modulating cellular processes
governed by the actin cytoskeleton in the intracellular life cycle of this
pathogen.
| Identifer | oai:union.ndltd.org:purdue.edu/oai:figshare.com:article/7391237 |
| Date | 04 January 2019 |
| Creators | Yao Liu (5930000) |
| Source Sets | Purdue University |
| Detected Language | English |
| Type | Text, Thesis |
| Rights | CC BY 4.0 |
| Relation | https://figshare.com/articles/MODULATION_OF_HOST_ACTIN_CYTOSKELETON_BY_A_LEGIONELLA_PNEUMOPHILA_EFFECTOR/7391237 |
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