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

Abstract

Methicillin-resistant <i>Staphylococcus aureus</i> (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. Having said that, Antibacterial effect of ketamine against MRSA strains, its mechanism of action and in silico interaction with sortase A was evaluated. The antibacterial effect of ketamine was assessed by 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 to 3.73 mM. Their mechanism of action involves alterations in the membrane integrity and DNA damage, reducing cell viability that provoke death by apoptosis. In addition, Ketamine compound had affinity for S. aureus sortase A. These results indicate that this compound can be an alternative to develop new strategies to combat of infections caused by MRSA.

Ketamine-based Sedation Use in Mechanically Ventilated Critically Ill Patients with COVID-19: A Multicenter Cohort Study

“…ketamine has also been demonstrated to be involved in the growth-inhibiting activity of serious infections acquired in hospitals, such as methicillin-resistant Staphylococcus aureus (MRSA). ( Coutinho et al, 2021 ). Also, our cohort's reduced length of hospital stay might have contributed to the overall risk of acquiring hospital infection owing to less exposure.…”

Improving the treatment of bacterial infections caused by multidrug-resistant bacteria through drug repositioning

“…This enzyme is responsible for the acquisition of iron from host cells, the adhesion of bacteria to the extracellular matrix of the host, and the evasion of its immune system. A similar mechanism of antibacterial activity occurs in the case of lidocaine and procaine, these damage the bacterial cell membrane, leading to changes in permeability and ion outflow within the bacterial cell (Coutinho et al, 2021). An ongoing clinical trial (NCT04843982, in the recruitment phase) aims to evaluate the anti-inflammatory effect of one of the ketamine stereoisomers in the acute phase of sepsis.…”

“…Some anesthetic drugs also have antimicrobial activity. In vitro, studies have confirmed the effectiveness of ketamine against strains of P. aeruginosa, E. faecalis, S. pyogenes, S. epidermidis and S. aureus, including those resistant to methicillin (Begec et al, 2013;Coutinho et al, 2021;Sokolowska et al, 2023). The drug is believed to induce apoptosis by altering the integrity of the cell membrane and damaging bacterial DNA.…”