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Experimental Endocarditis Model of Methicillin Resistant Staphylococcus aureus MRSA in Rat
Published on: June 4, 2012
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.
Abstract:
Methicillin-resistant Staphylococcus aureus (MRSA) is one of the main human pathogens and is responsible for many diseases, ranging from skin infections to more invasive infections. These infections are dangerous and expensive to treat because these strains are resistant to a large number of conventional antibiotics. Thus, the antibacterial effect of ketamine against MRSA strains, its mechanism of action, and in silico interaction with sortase A were evaluated. The antibacterial effect of ketamine was assessed using the broth microdilution method. Subsequently, the mechanism of action was assessed using flow cytometry and molecular docking assays with sortase A. Our results showed that ketamine has a significant antibacterial activity against MRSA strains in the range of 2.49-3.73 mM. Their mechanism of action involves alterations in membrane integrity and DNA damage, reducing cell viability, and inducing apoptosis. In addition, ketamine had an affinity for S. aureus sortase A. These results indicate that this compound can be used as an alternative to develop new strategies to combat infections caused by MRSA.
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.

