Perturbation of genome integrity to fight pathogenic microorganisms

Kinga Nyíri, B. Vértessy

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Background: Resistance against antibiotics is unfortunately still a major biomedical challenge for a wide range of pathogens responsible for potentially fatal diseases. Scope of review: In this study, we aim at providing a critical assessment of the recent advances in design and use of drugs targeting genome integrity by perturbation of thymidylate biosynthesis. Major conclusion: We find that research efforts from several independent laboratories resulted in chemically highly distinct classes of inhibitors of key enzymes within the routes of thymidylate biosynthesis. The present article covers numerous studies describing perturbation of this metabolic pathway in some of the most challenging pathogens like Mycobacterium tuberculosis, Plasmodium falciparum, and Staphylococcus aureus. General significance: Our comparative analysis allows a thorough summary of the current approaches to target thymidylate biosynthesis enzymes and also include an outlook suggesting novel ways of inhibitory strategies. This article is part of a Special Issue entitled "Science for Life" Guest Editor: Dr. Austen Angell, Dr. Salvatore Magazù and Dr. Federica Migliardo.

Original languageEnglish
JournalBiochimica et Biophysica Acta - General Subjects
DOIs
Publication statusAccepted/In press - Mar 3 2016

Fingerprint

Biological Science Disciplines
Biosynthesis
Enzyme Inhibitors
Plasmodium falciparum
Drug Delivery Systems
Microbial Drug Resistance
Metabolic Networks and Pathways
Mycobacterium tuberculosis
Microorganisms
Staphylococcus aureus
Genes
Genome
Pathogens
Enzymes
Research
Anti-Bacterial Agents

Keywords

  • DNA repair
  • Drug resistance
  • DUTPase
  • Mycobacteria
  • Plasmodium
  • Thymidylate biosynthesis
  • Thymidylate synthase
  • ThyX

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

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abstract = "Background: Resistance against antibiotics is unfortunately still a major biomedical challenge for a wide range of pathogens responsible for potentially fatal diseases. Scope of review: In this study, we aim at providing a critical assessment of the recent advances in design and use of drugs targeting genome integrity by perturbation of thymidylate biosynthesis. Major conclusion: We find that research efforts from several independent laboratories resulted in chemically highly distinct classes of inhibitors of key enzymes within the routes of thymidylate biosynthesis. The present article covers numerous studies describing perturbation of this metabolic pathway in some of the most challenging pathogens like Mycobacterium tuberculosis, Plasmodium falciparum, and Staphylococcus aureus. General significance: Our comparative analysis allows a thorough summary of the current approaches to target thymidylate biosynthesis enzymes and also include an outlook suggesting novel ways of inhibitory strategies. This article is part of a Special Issue entitled {"}Science for Life{"} Guest Editor: Dr. Austen Angell, Dr. Salvatore Magaz{\`u} and Dr. Federica Migliardo.",
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AU - Vértessy, B.

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N2 - Background: Resistance against antibiotics is unfortunately still a major biomedical challenge for a wide range of pathogens responsible for potentially fatal diseases. Scope of review: In this study, we aim at providing a critical assessment of the recent advances in design and use of drugs targeting genome integrity by perturbation of thymidylate biosynthesis. Major conclusion: We find that research efforts from several independent laboratories resulted in chemically highly distinct classes of inhibitors of key enzymes within the routes of thymidylate biosynthesis. The present article covers numerous studies describing perturbation of this metabolic pathway in some of the most challenging pathogens like Mycobacterium tuberculosis, Plasmodium falciparum, and Staphylococcus aureus. General significance: Our comparative analysis allows a thorough summary of the current approaches to target thymidylate biosynthesis enzymes and also include an outlook suggesting novel ways of inhibitory strategies. This article is part of a Special Issue entitled "Science for Life" Guest Editor: Dr. Austen Angell, Dr. Salvatore Magazù and Dr. Federica Migliardo.

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KW - Drug resistance

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KW - Thymidylate synthase

KW - ThyX

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