Secretome of obligate intracellular Rickettsia

Joseph J Gillespie1, Simran J Kaur2, M Sayeedur Rahman2

  • 1Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, USA jgillespie@som.umaryland.edu.

Insights

Rickettsia bacteria are intracellular parasites causing emerging infectious diseases. This review details their secreted proteins and secretion systems, identifying gaps in understanding protein pathways crucial for pathogenicity.

Area of Science:

  • Microbiology and Infectious Diseases
  • Molecular Biology
  • Bioinformatics

Background:

  • Rickettsia are obligate intracellular parasites causing emerging infectious diseases and potential bioterrorism threats.
  • Current treatments for Rickettsia infections rely on antibiotics, and no effective vaccines are commercially available.
  • Understanding Rickettsia pathogenicity mechanisms is crucial, with a focus on secreted proteins interacting with host cells.

Purpose of the Study:

  • To comprehensively review the Rickettsia secretome, including secretion systems and characterized secretory proteins.
  • To provide novel structural and functional insights into Rickettsia secretion systems using bioinformatics and phylogenomics.
  • To identify unassigned secretory proteins and poorly understood signal sequences involved in Rickettsia pathogenicity.

Main Methods:

  • Systematic review of all known Rickettsia secretion systems and characterized secretory proteins.
  • Bioinformatic and phylogenomic analyses to elucidate structural and functional aspects of secretion systems.
  • Identification of potential moonlighting proteins on Rickettsia surfaces.

Main Results:

  • Detailed characterization of six Rickettsia secretion systems and 19 secretory proteins.
  • Identification of potential moonlighting proteins involved in Rickettsia-host interactions.
  • Discovery that most characterized secretory proteins are not assigned to their cognate secretion pathways.
  • Poor understanding of signal sequences mediating protein translocation for most secretion pathways.

Conclusions:

  • This review serves as a blueprint for understanding Rickettsia protein translocation pathways.
  • It will aid in linking characterized secreted proteins to their specific secretion systems.
  • The findings facilitate the identification of novel secreted proteins critical for Rickettsia's intracellular lifestyle and pathogenicity.

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