title: Effect of 4-methoxy 1-methyl 2-oxopyridine 3-carbamide on Staphylococcus aureus by inhibiting UDP-MurNAc-pentapeptide, peptidyl deformylase and uridine monophosphate kinase.
abstract: OBJECTIVE
  The present study aimed to investigate the anti-Staphylococcus aureus and anti-biofilm properties of 4-methoxy-1-methyl-2-oxopyridine-3-carbamide (MMOXC) on S. aureus UDP-MurNAc-pentapeptide (MurF), peptidyl deformylase (PDF) and uridine monophosphate kinase (UMPK).
  
  
  RESULTS
  The in vitro efficacy of MMOXC was evaluated using quantitative polymerase chain reaction, in vitro assays and broth microdilution methods. Further, the minimum inhibitory concentration (MIC), IC50and zone of inhibition were recorded in addition to the anti-biofilm property. MMOXC inhibited pure recombinant UMPK and PDF enzymes with a Kiof 0·37 and 0·49 μmol l-1. However Kiwas altered for MurF with varying substrates. The MurF Kifor UMT, d-Ala-d-Ala and ATP as substrates was 0·3, 0·25 and 1·4 μmol l-1, respectively. Real-time PCR analysis showed a significant reduction in PDF and MurF expression which correlated with the MIC90at 100 μmol l-1and IC50in the range 42 ± 1·5 to 50 ± 1 μmol l-1against all strains tested. At 5 μmol l-1MMOXC was able completely to remove preformed biofilms of S. aureus and other drug resistant strains.
  
  
  CONCLUSIONS
  MMOXC was able to kill S. aureus and drug resistant strains tested by inhibiting MurF, UMPK and PDF enzymes and completely obliterated preformed biofilms.
  
  
  CONCLUSIONS
  Growth reduction and biofilm removal are prerequisites for controlling S. aureus infections. In this study MMOXC exhibited prominent anti-S. aureus and anti-biofilm properties by blocking cell wall formation, RNA biosynthesis and protein maturation.
authors.affiliation: Department of Biotechnology, Sri Venkateswara Institute of Medical Sciences, Tirupati, India.
authors.forename: V
authors.initials: V
authors.lastname: Swarupa
authors.affiliation: Department of Microbiology, Sri Venkateswara Institute of Medical Sciences, Tirupati, India.
authors.forename: A
authors.initials: A
authors.lastname: Chaudhury
authors.affiliation: Department of Biotechnology, Sri Venkateswara Institute of Medical Sciences, Tirupati, India.
authors.forename: P V G
authors.initials: PV
authors.lastname: Krishna Sarma
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D009703:Nucleoside-Phosphate Kinase / Q000037:antagonists & inhibitors*; D060888:Real-Time Polymerase Chain Reaction; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D014508:Urea / Q000378:metabolism / Q000494:pharmacology*; D014538:Uridine Diphosphate N-Acetylmuramic Acid / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors
chemical_list: D000900:Anti-Bacterial Agents; D014538:Uridine Diphosphate N-Acetylmuramic Acid; C002225:UDP-N-acetylmuramic acid pentapeptide; D014508:Urea; C023276:uridine monophosphate kinase; D009703:Nucleoside-Phosphate Kinase
keywords: 
  IC
  50
  ; 
  K
  i
  ; 
  MIC
  ; 
  PCR
  ; anti-biofilm; real-time ZOI