Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 102, Issue 5, Pages 1673-1678Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0406873102
Keywords
macrophage; secretory pathway; endoplasmic reticulum; pathogenesis
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The pathogen Brucella abortus resides inside macrophages within a unique, replication-permissive organelle that is derived from the endoplasmic reticulum (ER). Although dependent on the Brucella type IV secretion system VirB, the mechanisms governing the biogenesis of this compartment remain elusive. Here, we investigated a putative role of the early secretory pathway in ER membrane accretion by the Brucella-containing vacuoles (BCVs). We show that BCVs interact with ER exit sites (ERES), and blockade of Sar1 activity, which disrupts ERES, prevents intracellular replication of Brucella. In cells expressing the dominant interfering form Sar1[T39N], BCVs do not acquire ER membranes, suggesting that they are unable to mature into replicative organelles. By contrast, treatments that block subsequent secretory events do not affect bacterial replication. We propose that Sar1-dependent ERES functions, but not subsequent secretory events, are essential for the biogenesis of the Brucella replicative compartment and, thus, bacterial replication. These results assign an essential role for Sar1 in pathogenesis of an intracellular bacterium.
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