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Mitochondrial antibiograms in personalized medicine.

David Pacheu-Grau1, Aurora Gómez-Durán, Eldris Iglesias

  • 1Departamento de Bioquímica, Biologa Molecular y Celular, Universidad de Zaragoza, 50013 Zaragoza, Spain.

Human Molecular Genetics
|December 11, 2012
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Summary

Mitochondrial DNA (mtDNA) variations influence patient responses to ribosomal antibiotics. Certain genetic variations in mitochondrial ribosomes can cause adverse drug reactions, suggesting personalized antibiotic therapy based on mitochondrial antibiograms.

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Area of Science:

  • Pharmacogenomics
  • Mitochondrial Biology
  • Bacterial Infections

Background:

  • Ribosomal antibiotics combat bacteria but can cause adverse drug reactions.
  • Mitochondrial ribosomes, due to endosymbiotic origins, are unintended targets of these antibiotics.
  • Genetic variations in individuals may contribute to antibiotic sensitivity.

Purpose of the Study:

  • To investigate if specific mitochondrial DNA (mtDNA) haplogroup polymorphisms cause off-target effects of ribosomal antibiotics.
  • To analyze the impact of these interactions on mitochondrial protein synthesis and oxygen consumption.

Main Methods:

  • Constructed 25 transmitochondrial cell lines from individuals with high-frequency European mtDNA haplogroups.
  • Cultured cell lines with and without common ribosomal antibiotics.
  • Assessed mitochondrial protein synthesis and oxygen consumption.

Main Results:

  • Linezolid treatment significantly reduced mitochondrial translation products in cybrids with the m.3010A allele.
  • Ratios of key mitochondrial respiratory proteins (p.MT-CO1/SDHA, Complex IV/CS) were lower in cybrids with the m.3010A allele after linezolid exposure.

Conclusions:

  • Specific mtDNA polymorphisms, like m.3010A, can lead to adverse effects from ribosomal antibiotics.
  • Implementing mitochondrial antibiograms for common mtDNA polymorphisms and antibiotics is recommended for personalized medicine.
  • This approach can help avoid side effects and optimize antibiotic therapy.