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Measurement of Heme Synthesis Levels in Mammalian Cells
09:43

Measurement of Heme Synthesis Levels in Mammalian Cells

Published on: July 9, 2015

Two coregulated efflux transporters modulate intracellular heme and protoporphyrin IX availability in Streptococcus

Annabelle Fernandez1, Delphine Lechardeur, Aurélie Derré-Bobillot

  • 1Institut National de la Recherche Agronomique, UMR1319 Micalis, Bâtiment 222, Domaine de Vilvert, Jouy-en-Josas, France. annabelle.fernandez@jouy.inra.fr

Plos Pathogens
|April 28, 2010
PubMed

Insights

Streptococcus agalactiae scavenges heme for virulence. New efflux systems (pefA-pefB, pefR-pefC-pefD) regulate heme and protoporphyrin IX (PPIX) levels, crucial for bacterial respiration and infection.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Pathogenesis

Background:

  • Streptococcus agalactiae is a significant neonatal pathogen causing septicemia.
  • The bacterium requires scavenged heme for respiration and virulence but lacks heme synthesis pathways.
  • Mechanisms regulating intracellular heme and protoporphyrin IX (PPIX) in S. agalactiae remain uncharacterized.

Purpose of the Study:

  • To identify and characterize the regulatory mechanisms controlling heme and PPIX homeostasis in Streptococcus agalactiae.
  • To investigate the role of novel efflux systems in managing intracellular porphyrin levels.
  • To determine the impact of these systems on bacterial respiration and virulence.

Main Methods:

  • Identification and characterization of two novel operons (pefA-pefB and pefR-pefC-pefD) involved in porphyrin efflux.
  • In vitro and in vivo assays to assess bacterial phenotypes, including porphyrin sensitivity and virulence.
  • Analysis of PefR, a MarR-superfamily repressor, and its interaction with heme and PPIX.

Main Results:

  • Two new operons, pefA-pefB and pefR-pefC-pefD, mediate heme and PPIX efflux in S. agalactiae.
  • PefR acts as a repressor for both operons, with repression alleviated by heme or PPIX.
  • Mutants lacking both efflux systems show increased sensitivity to porphyrins and intracellular accumulation.
  • A DeltapefR mutant exhibits defective heme-dependent respiration and reduced virulence.

Conclusions:

  • A novel efflux regulon, controlled by PefR, is essential for regulating intracellular heme and PPIX availability in S. agalactiae.
  • This efflux system is critical for enabling heme-dependent respiration and host infection by the pathogen.
  • Understanding these heme homeostasis mechanisms offers potential targets for combating neonatal infections.

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