loading page

Mycobacterium Tuberculosis Protein PE17 Induces Organelle Disruptions Upon Heterologous Expression in A549 Human Airway Epithelial Cells
  • +5
  • Allyson T. Loy,
  • Lucinda N. Shaffer,
  • Sophia T. Gavalas,
  • Anna A. Mermilliod,
  • Frederick Quinn,
  • Adrian J. Wolstenholme,
  • Barbara J. Reaves,
  • Vincent Starai
Allyson T. Loy
University of Georgia Department of Microbiology
Author Profile
Lucinda N. Shaffer
University of Georgia Department of Microbiology
Author Profile
Sophia T. Gavalas
University of Georgia Department of Microbiology
Author Profile
Anna A. Mermilliod
University of Georgia Department of Microbiology
Author Profile
Frederick Quinn
University of Georgia Department of Infectious Diseases
Author Profile
Adrian J. Wolstenholme
University of Georgia Department of Infectious Diseases
Author Profile
Barbara J. Reaves
University of Georgia Department of Infectious Diseases
Author Profile
Vincent Starai
University of Georgia Department of Microbiology

Corresponding Author:[email protected]

Author Profile

Abstract

Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis. Its success as a pathogen is dependent on an arsenal of secreted virulence factors which target host cell organelles. In this report, we have characterized the effects of two proteins known to be secreted by Mtb on eukaryotic mitochondria: ESAT-6 and a member of the poorly-described PE/PPE protein family, PE17. Intracellular expression of ESAT-6 in A549 cells did not induce mitochondrial fragmentation. In contrast, expression of PE17 caused extensive mitochondrial fragmentation and an overall reduction in mass. Further characterization of the effects of PE17 within host cells revealed a dramatic decrease in the mass of the trans-Golgi network and the Golgi stack with lesser but significant decreases in late endosomes and lysosomes. The endoplasmic reticulum and organelles of the early endocytic pathway were not significantly affected. PE17 specifically colocalized with large, cytoplasmic lipid droplets via a C-terminal domain, suggesting a significant role for PE17 in the disruption of multiple host cell organelles and a novel interaction with host lipid droplets.
16 Feb 2023Submitted to Molecular Microbiology
17 Feb 2023Submission Checks Completed
17 Feb 2023Assigned to Editor
18 Feb 2023Reviewer(s) Assigned
12 Mar 2023Review(s) Completed, Editorial Evaluation Pending
13 Mar 2023Editorial Decision: Revise Minor