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Interactions of attenuated Mycobacterium tuberculosis phoP mutant with human macrophages

Nadia L Ferrer1, Ana B Gomez, Olivier Neyrolles

  • 1Grupo de Genética de Micobacterias, Departamento de Microbiología, Medicina Preventiva y Salud Pública, Universidad de Zaragoza, Zaragoza, Spain.

Plos One
|October 2, 2010
PubMed
Abstract

Insights

The Mycobacterium tuberculosis phoP mutant SO2 shows increased binding to human macrophages and reduced intracellular growth, suggesting potential as an attenuated tuberculosis vaccine candidate.

Area of Science:

  • Immunology
  • Microbiology
  • Vaccinology

Background:

  • Mycobacterium tuberculosis (M. tuberculosis) phoP mutant SO2, derived from a clinical isolate, is attenuated in murine models.
  • This attenuation suggests SO2's potential as a live-attenuated vaccine candidate against tuberculosis.

Purpose of the Study:

  • To investigate the adhesion, intracellular replication, and trafficking of M. tuberculosis SO2 in human macrophages.
  • To compare SO2's behavior with the wild-type M. tuberculosis strain in a human cellular context.

Main Methods:

  • Analysis of SO2 adhesion to human monocyte-derived macrophages and THP-1 cells.
  • Assessment of intracellular replication and trafficking of SO2 within human macrophages.
  • Comparison of SO2 with wild-type M. tuberculosis regarding nitric oxide (NO) susceptibility.

Main Results:

  • SO2 exhibited enhanced adhesion to human phagocytic cells compared to the wild-type strain.
  • Impaired intracellular replication of SO2 was observed in both monocyte-derived macrophages and THP-1 cells.
  • Intracellular trafficking analysis indicated SO2 has an impaired ability to block phagosome-lysosome fusion.

Conclusions:

  • M. tuberculosis SO2 demonstrates enhanced binding to human macrophages and altered intracellular trafficking.
  • The study discusses the altered lipid profile and ESAT-6 secretion of the phoP mutant SO2 in relation to its attenuation.
  • Findings support SO2's potential as an attenuated vaccine candidate against tuberculosis.

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