Screening Mycobacterium tuberculosis secreted proteins identifies Mpt64 as a eukaryotic membrane-binding bacterial effector

Chelsea E. Stamm, Breanna L. Pasko, Sujittra Chaisavaneeyakorn, Luis H. Franco, Vidhya R. Nair, Bethany A. Weigele, Neal M Alto, Michael U Shiloh

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis, is one of the most successful human pathogens. One reason for its success is that Mtb can reside within host macrophages, a cell type that normally functions to phagocytose and destroy infectious bacteria. However, Mtb is able to evade macrophage defenses in order to survive for prolonged periods of time. Many intracellular pathogens secrete virulence factors targeting host membranes and organelles to remodel their intracellular environmental niche. We hypothesized that Mtb secreted proteins that target host membranes are vital for Mtb to adapt to and manipulate the host environment for survival. Thus, we characterized 200 secreted proteins from Mtb for their ability to associate with eukaryotic membranes using a unique temperature-sensitive yeast screen and to manipulate host trafficking pathways using a modified inducible secretion screen. We identified five Mtb secreted proteins that both associated with eukaryotic membranes and altered the host secretory pathway. One of these secreted proteins, Mpt64, localized to the endoplasmic reticulum during Mtb infection of murine and human macrophages and impaired the unfolded protein response in macrophages. These data highlight the importance of secreted proteins in Mtb pathogenesis and provide a basis for further investigation into their molecular mechanisms.

Original languageEnglish (US)
Article numbere00354-19
JournalmSphere
Volume4
Issue number3
DOIs
StatePublished - May 1 2019

Fingerprint

Mycobacterium tuberculosis
Membranes
Proteins
Macrophages
Unfolded Protein Response
Mycobacterium Infections
Secretory Pathway
Virulence Factors
Phagocytosis
Endoplasmic Reticulum
Organelles
Tuberculosis
Yeasts
Bacteria
Temperature
Survival

Keywords

  • Effector functions
  • Mycobacterium tuberculosis
  • Pathogenesis

ASJC Scopus subject areas

  • Microbiology
  • Molecular Biology

Cite this

Screening Mycobacterium tuberculosis secreted proteins identifies Mpt64 as a eukaryotic membrane-binding bacterial effector. / Stamm, Chelsea E.; Pasko, Breanna L.; Chaisavaneeyakorn, Sujittra; Franco, Luis H.; Nair, Vidhya R.; Weigele, Bethany A.; Alto, Neal M; Shiloh, Michael U.

In: mSphere, Vol. 4, No. 3, e00354-19, 01.05.2019.

Research output: Contribution to journalArticle

Stamm, Chelsea E. ; Pasko, Breanna L. ; Chaisavaneeyakorn, Sujittra ; Franco, Luis H. ; Nair, Vidhya R. ; Weigele, Bethany A. ; Alto, Neal M ; Shiloh, Michael U. / Screening Mycobacterium tuberculosis secreted proteins identifies Mpt64 as a eukaryotic membrane-binding bacterial effector. In: mSphere. 2019 ; Vol. 4, No. 3.
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