Skip to main content
placeholder image

Propyl-5-hydroxy-3-methyl-1-phenyl-1H-pyrazole-4-carbodithioate (HMPC): A new bacteriostatic agent against methicillin - Resistant Staphylococcus aureus

Journal Article


Abstract


  • The emergence of Staphylococcus aureus strains resistant to 'last resort' antibiotics compels the development of new antimicrobials against this important human pathogen. We found that propyl 5-hydroxy-3-methyl-1-phenyl-1H-pyrazole-4-carbodithioate (HMPC) shows bacteriostatic activity against S. aureus (MIC = 4 μg/ml) and rescues Caenorhabditis elegans from S. aureus infection. Whole-genome sequencing of S. aureus mutants resistant to the compound, along with screening of a S. aureus promoter-lux reporter array, were used to explore possible mechanisms of action. All mutants resistant to HMPC acquired missense mutations at distinct codon positions in the global transcriptional regulator mgrA, followed by secondary mutations in the phosphatidylglycerol lysyltransferase fmtC/mprF. The S. aureus promoter-lux array treated with HMPC displayed a luminescence profile that was unique but showed similarity to DNA-damaging agents and/or DNA replication inhibitors. Overall, HMPC is a new anti-staphylococcal compound that appears to act via an unknown mechanism linked to the global transcriptional regulator MgrA.

Authors


  •   Johnston, Tatiana (external author)
  •   Van Tyne, Daria (external author)
  •   Chen, Roy Fangxing (external author)
  •   Fawzi, Nicolas (external author)
  •   Kwon, Bumsup (external author)
  •   Kelso, Michael J.
  •   Gilmore, Michael (external author)
  •   Mylonakis, Eleftherios (external author)

Publication Date


  • 2018

Citation


  • Johnston, T., Van Tyne, D., Chen, R. F., Fawzi, N. L., Kwon, B., Kelso, M. J., Gilmore, M. S. & Mylonakis, E. (2018). Propyl-5-hydroxy-3-methyl-1-phenyl-1H-pyrazole-4-carbodithioate (HMPC): A new bacteriostatic agent against methicillin - Resistant Staphylococcus aureus. Scientific Reports, 8 (1), 7062-7062.

Scopus Eid


  • 2-s2.0-85046622444

Number Of Pages


  • 0

Start Page


  • 7062

End Page


  • 7062

Volume


  • 8

Issue


  • 1

Place Of Publication


  • United Kingdom

Abstract


  • The emergence of Staphylococcus aureus strains resistant to 'last resort' antibiotics compels the development of new antimicrobials against this important human pathogen. We found that propyl 5-hydroxy-3-methyl-1-phenyl-1H-pyrazole-4-carbodithioate (HMPC) shows bacteriostatic activity against S. aureus (MIC = 4 μg/ml) and rescues Caenorhabditis elegans from S. aureus infection. Whole-genome sequencing of S. aureus mutants resistant to the compound, along with screening of a S. aureus promoter-lux reporter array, were used to explore possible mechanisms of action. All mutants resistant to HMPC acquired missense mutations at distinct codon positions in the global transcriptional regulator mgrA, followed by secondary mutations in the phosphatidylglycerol lysyltransferase fmtC/mprF. The S. aureus promoter-lux array treated with HMPC displayed a luminescence profile that was unique but showed similarity to DNA-damaging agents and/or DNA replication inhibitors. Overall, HMPC is a new anti-staphylococcal compound that appears to act via an unknown mechanism linked to the global transcriptional regulator MgrA.

Authors


  •   Johnston, Tatiana (external author)
  •   Van Tyne, Daria (external author)
  •   Chen, Roy Fangxing (external author)
  •   Fawzi, Nicolas (external author)
  •   Kwon, Bumsup (external author)
  •   Kelso, Michael J.
  •   Gilmore, Michael (external author)
  •   Mylonakis, Eleftherios (external author)

Publication Date


  • 2018

Citation


  • Johnston, T., Van Tyne, D., Chen, R. F., Fawzi, N. L., Kwon, B., Kelso, M. J., Gilmore, M. S. & Mylonakis, E. (2018). Propyl-5-hydroxy-3-methyl-1-phenyl-1H-pyrazole-4-carbodithioate (HMPC): A new bacteriostatic agent against methicillin - Resistant Staphylococcus aureus. Scientific Reports, 8 (1), 7062-7062.

Scopus Eid


  • 2-s2.0-85046622444

Number Of Pages


  • 0

Start Page


  • 7062

End Page


  • 7062

Volume


  • 8

Issue


  • 1

Place Of Publication


  • United Kingdom