title: Perturbation of genome integrity to fight pathogenic microorganisms.
abstract: Resistance against antibiotics is unfortunately still a major biomedical challenge for a wide range of pathogens responsible for potentially fatal diseases.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Dept. Biotechnology, Budapest University of Technology and Economics, 4 Szent Gellért tér, Budapest HU 1111, Hungary; Institute of Enzymology, RCNS, Hungarian Academy of Sciences, 2 Magyar tudósok körútja, Budapest HU 1117, Hungary. Electronic address: nyiri.kinga@ttk.mta.hu.
authors.forename: Kinga
authors.initials: K
authors.lastname: Nyíri
authors.affiliation: Dept. Biotechnology, Budapest University of Technology and Economics, 4 Szent Gellért tér, Budapest HU 1111, Hungary; Institute of Enzymology, RCNS, Hungarian Academy of Sciences, 2 Magyar tudósok körútja, Budapest HU 1117, Hungary. Electronic address: vertessy@mail.bme.hu.
authors.forename: Beáta G
authors.initials: BG
authors.lastname: Vértessy
mesh_terms: D000818:Animals; D001419:Bacteria / Q000201:enzymology / Q000235:genetics* / Q000472:pathogenicity*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D042822:Genomic Instability; D010271:Parasites / Q000235:genetics* / Q000472:pathogenicity*; D014780:Viruses / Q000235:genetics* / Q000472:pathogenicity*
chemical_list: D004791:Enzyme Inhibitors
keywords: DNA repair; Mycobacteria; Plasmodium; ThyX; Thymidylate biosynthesis; Thymidylate synthase; dUTPase; drug resistance