Oxidation of macrophage membrane cholesterol by intracellular Rhodococcus equi

R Linder1, A W Bernheimer

  • 1School of Health Sciences, Hunter College, City University of New York, New York 10010, USA.

Insights

Virulent Rhodococcus equi survives within macrophages by oxidizing cholesterol, while non-virulent strains are eliminated. Cooperative bacterial toxins may enhance host tissue damage.

Area of Science:

  • Microbiology
  • Immunology
  • Biochemistry

Background:

  • Bacterial pathogens can evade host immune responses through various mechanisms.
  • Cholesterol oxidase is an enzyme produced by some bacteria that can modify host cell membranes.
  • Cooperation between bacterial species can lead to enhanced virulence and host tissue damage.

Purpose of the Study:

  • To investigate the role of cholesterol oxidase in the intracellular survival of Rhodococcus equi within macrophages.
  • To determine the effect of co-infection with Corynebacterium pseudotuberculosis on R. equi survival and cholesterol oxidation.
  • To explore the contribution of cooperative bacterial toxins to host tissue damage.

Main Methods:

  • Phagocytosis assays using cultured mouse macrophages (PD388D1) and virulent (ATCC 33701) and non-virulent (4219) strains of Rhodococcus equi.
  • Measurement of intracellular bacterial survival and macrophage membrane cholesterol oxidation.
  • Co-phagocytosis experiments with R. equi and Corynebacterium pseudotuberculosis, followed by analysis of oxidation products.

Main Results:

  • Virulent R. equi, producing cholesterol oxidase, survived intracellularly and oxidized macrophage membrane cholesterol.
  • Non-virulent R. equi, lacking cholesterol oxidase, was eliminated by macrophages and did not cause cholesterol oxidation.
  • Co-phagocytosis of R. equi with C. pseudotuberculosis resulted in a 10-fold increase in cholesterol oxidation product (4-cholesten-3-one).

Conclusions:

  • Cholesterol oxidase production is crucial for the intracellular survival of virulent Rhodococcus equi in macrophages.
  • Cooperation between R. equi and C. pseudotuberculosis enhances bacterial virulence through synergistic action of their respective toxins.
  • Bacterial cooperative toxins play a significant role in mediating host tissue damage during infection.