Memantine hydrochloride promotes the antibacterial effect of neutrophils against methicillin-resistant Staphylococcus aureus and the related mechanism / 中华微生物学和免疫学杂志

ABSTRACT

Objective:To investigate whether memantine hydrochloride (MEM) could promote the bactericidal effect of neutrophils against methicillin-resistant Staphylococcus aureus (MRSA) and the possible mechanism. Methods:Neutrophils were co-incubated with different concentrations of MEM and MRSA for 4 h. Then the cell lysates were collected and cultured on plate for survival bacteria counting. After co-incubation, the neutrophils were collected to detect the production of reactive oxygen species (ROS) and the release of neutrophil extracellular traps (NETs). A mouse model of MRSA infection was established, and then the mice were treated with or without MEM. Blood, spleen and kidney samples were collected from the mice for bacterial colony counting and blood procalcitonin (PCT) detection. In the 48 h survival experiment, the mice were first infected with MRSA, and then treated with MEM or PBS. The survival rates of the mice were calculated and the survival curves were drawn.Results:The number of MRSA co-cultured with neutrophils decreased significantly in the presence of MEM, and within a certain concentration range, the survival number of MRSA decreased with the increase of MEM concentration. Moreover, MEM could significantly promote the production of ROS by neutrophils and the formation of NETs. In vivo experiment showed that the concentration of PCT in mouse blood samples was lower in the MRSA+ MEM group than in the MRSA+ PBS group. The animal experiment also revealed that MEM significantly decreased the bacteria loads in mouse blood and organs and increased the 48 h survival rate after MRSA infection.Conclusions:MEM could significantly promote the bactericidal effect of neutrophils against MRSA, which might be related to the enhanced generation of ROS by neutrophils and the formation of NETs.