Role of PPE18 protein in intracellular survival and pathogenicity of Mycobacterium tuberculosis in mice

PLoS One. 2012;7(12):e52601. doi: 10.1371/journal.pone.0052601. Epub 2012 Dec 28.

Abstract

Background: Ever since its discovery the mycobacterial proline-proline-glutamic acid (PPE) family of proteins has generated a huge amount of interest. Understanding the role of these proteins in the pathogenesis of Mycobacterium tuberculosis (Mtb) is important. We have demonstrated earlier that the PPE18 protein of Mtb induces IL-10 production in macrophages with subsequent downregulation of pro-inflammatory cytokines like IL-12 and TNF-α and favors a T-helper (Th) 2-type of immune response.

Methodology/principal findings: Using a ppe18 genetic knock-out Mtb strain, we have now carried out infection studies in mice to understand the role of PPE18 in Mtb virulence. The studies reveal that lack of PPE18 leads to attenuation of Mtb in vivo. Mice infected with the ppe18 deleted strain have reduced infection burden in lung, liver and spleen and have better survival rates compared to mice infected with the wild-type Mtb strain.

Conclusions/significance: Taken together our data suggest that PPE18 could be a crucial virulence factor for intracellular survival of Mtb.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Bacterial / genetics
  • Antigens, Bacterial / metabolism*
  • Antigens, Bacterial / physiology
  • Bacterial Load
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Bacterial Proteins / physiology
  • Female
  • Gene Knockout Techniques
  • Host-Pathogen Interactions
  • Liver / microbiology
  • Liver / pathology
  • Lung / microbiology
  • Lung / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microbial Viability
  • Mycobacterium tuberculosis / metabolism
  • Mycobacterium tuberculosis / pathogenicity
  • Mycobacterium tuberculosis / physiology*
  • Spleen / microbiology
  • Spleen / pathology
  • Tuberculosis, Pulmonary / microbiology*
  • Virulence

Substances

  • Antigens, Bacterial
  • Bacterial Proteins
  • Rv1196 protein, Mycobacterium tuberculosis

Grant support

This work was supported by the grants (BT/PR/7890/MED/14/1171/2006 and BT/01/COE/07/02) from Department of Biotechnology (DBT), Government of India and a core grant to Centre for DNA Fingerprinting and Diagnostics (CDFD), India by DBT. This work was also supported by research fellowship to KHB from the Council of Scientific and Industrial Research (CSIR), India and by DBT Research Associateship in Biotechnology and Life Sciences to AA from the Department of Biotechnology (DBT), Government of India. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.