Antimicrobial activity of hydralazine against methicillin-resistant and methicillin-susceptible Staphylococcus aureus

Future Microbiol. 2024 Jan:19:91-106. doi: 10.2217/fmb-2023-0160. Epub 2024 Jan 31.

Abstract

Background: Staphylococcus aureus is a human pathogen responsible for high mortality rates. The development of new antimicrobials is urgent. Materials & methods: The authors evaluated the activity of hydralazine along with its synergism with other drugs and action on biofilms. With regard to action mechanisms, the authors evaluated cell viability, DNA damage and molecular docking. Results: MIC and minimum bactericidal concentration values ranged from 128 to 2048 μg/ml. There was synergism with oxacillin (50%) and vancomycin (25%). Hydralazine reduced the viability of biofilms by 50%. After exposure to hydralazine 2× MIC, 58.78% of the cells were unviable, 62.07% were TUNEL positive and 27.03% presented damage in the comet assay (p < 0.05). Hydralazine showed affinity for DNA gyrase and TyrRS. Conclusion: Hydralazine is a potential antibacterial.

Keywords: DNA fragmentation; MRSA; MSSA; TyrRS; gyrase A; hydralazine; repurposing.

Plain language summary

Staphylococcus aureus is a bacterium that can cause infection. Infections of S. aureus are becoming difficult to treat, but developing new drugs is a challenge. Repurposing them may be easier. This study looks at the possibility of using hydralazine, a type of medicine used to treat high blood pressure, against S. aureus. The authors found that hydralazine can kill S. aureus and can be used with other antibiotics, including oxacillin and vancomycin. Hydralazine interferes with important processes for the multiplication and survival of this bacterium. These results are preliminary but encouraging. Further studies are needed to confirm the use of hydralazine as a new treatment for S. aureus infections.

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Humans
  • Methicillin
  • Methicillin Resistance
  • Methicillin-Resistant Staphylococcus aureus*
  • Microbial Sensitivity Tests
  • Molecular Docking Simulation
  • Staphylococcal Infections* / drug therapy
  • Staphylococcal Infections* / microbiology
  • Staphylococcus aureus

Substances

  • Methicillin
  • Anti-Bacterial Agents