Burkholderia pseudomallei BicA protein promotes pathogenicity in macrophages by regulating invasion, intracellular survival, and virulence

Jacob L. Stockton, Nittaya Khakhum, Heather L. Stevenson, Alfredo G. Torres

Research output: Contribution to journalArticlepeer-review

Abstract

Burkholderia pseudomallei (Bpm) is the causative agent of melioidosis disease. Bpm is a facultative intracellular pathogen with a complex life cycle inside host cells. Pathogenic success depends on a variety of virulence factors with one of the most critical being the type 6 secretion system (T6SS). Bpm uses the T6SS to move into neighboring cells, resulting in multinucleated giant cell (MNGC) formation, a strategy used to disseminate from cell to cell. Our prior study using a dual RNA-seq analysis to dissect T6SS-mediated virulence on intestinal epithelial cells identifiedBicA as a factor upregulated in a T6SS mutant. BicA regulates both type 3 secretion system (T3SS) and T6SSs; however, the extent of its involvement during disease progression is unclear. To fully dissect the role of BicA during systemic infection, we used two macrophage cell lines paired with a pulmonary in vivo challenge murine model. We found that ΔbicA has a distinct intracellular replication defect in both immortalized and primary macrophages, which begins as early as 1 h post-infection. This intracellular defect is linked with the lackof cell-to-cell dissemination and MNGC formation as well as a defect in T3SS expression. The in vitro phenotype translated in vivo as ΔbicA was attenuated in a pulmonary model of infection, demonstrating a distinct macrophage activation profileand a lack of pathological features present in the wild type. Overall, these results highlight the role of BicA in regulating intracellular virulence and demonstrate that specificregulation of secretion systems has a significanteffecton host response and Bpm pathogenesis.

Original languageEnglish (US)
JournalmSphere
Volume8
Issue number5
DOIs
StatePublished - Oct 2023

Keywords

  • B. pseudomallei
  • BicA
  • invasion
  • macrophages
  • regulation
  • type 3 secretion system
  • type 6 secretion system

ASJC Scopus subject areas

  • Microbiology
  • Molecular Biology

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