Effect of 4‐methoxy 1‐methyl 2‐oxopyridine 3‐carbamide on Staphylococcus aureus by inhibiting UDP‐MurNAc‐pentapeptide, peptidyl deformylase and uridine monophosphate kinase
2017
Swarupa, V. | Chaudhury, A. | Krishna Sarma, P.V.G.
AIMS: 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). METHODS AND 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), IC₅₀ and zone of inhibition were recorded in addition to the anti‐biofilm property. MMOXC inhibited pure recombinant UMPK and PDF enzymes with a Kᵢ of 0·37 and 0·49 μmol l⁻¹. However Kᵢ was altered for MurF with varying substrates. The MurF Kᵢ for 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 MIC₉₀ at 100 μmol l⁻¹ and IC₅₀ in the range 42 ± 1·5 to 50 ± 1 μmol l⁻¹ against all strains tested. At 5 μmol l⁻¹ MMOXC 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. SIGNIFICANCE AND IMPACT OF THE STUDY: 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.
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