Effects of ketamine in methicillin-resistant Staphylococcus aureus and in silico interaction with sortase A

Tatiana do Nascimento Paiva Coutinho1, Fátima Daiana Dias Barroso2,3, Cecília Rocha da Silva2,3

  • 1Christus University Center (UNICHRISTUS), Fortaleza, CE, Brazil.

Insights

Ketamine shows significant antibacterial activity against Methicillin-resistant Staphylococcus aureus (MRSA) strains by damaging cell membranes and DNA. This suggests ketamine could be a potential alternative for developing new MRSA infection treatments.

Area of Science:

  • Microbiology
  • Pharmacology
  • Infectious Diseases

Background:

  • Methicillin-resistant Staphylococcus aureus (MRSA) is a major human pathogen causing difficult-to-treat infections due to antibiotic resistance.
  • Conventional antibiotics are often ineffective against MRSA, necessitating the search for novel therapeutic agents.

Purpose of the Study:

  • To evaluate the antibacterial effect of ketamine against MRSA strains.
  • To investigate the mechanism of action of ketamine.
  • To assess the in silico interaction of ketamine with Sortase A.

Main Methods:

  • Broth microdilution method to determine antibacterial activity.
  • Flow cytometry and molecular docking assays to elucidate the mechanism of action and interaction with Sortase A.

Main Results:

  • Ketamine demonstrated significant antibacterial activity against MRSA strains within a concentration range of 2.49-3.73 mM.
  • The mechanism involves disruption of membrane integrity, DNA damage, reduced cell viability, and induction of apoptosis.
  • Ketamine exhibited affinity for Staphylococcus aureus Sortase A.

Conclusions:

  • Ketamine possesses notable antibacterial properties against MRSA.
  • Its mechanism of action includes cellular damage and apoptosis induction.
  • Ketamine's interaction with Sortase A suggests potential as a novel therapeutic lead for MRSA infections.