D-Serine inhibits the attachment and biofilm formation of methicillin-resistant Staphylococcus aureus

• Published in: Biochemical and biophysical research communications 2021-01, Vol.537, p.50-56
• Main Authors: Iwata, Yasunori, Sakai, Norihiko, Yoneda, Ikuko, Senda, Yasuko, Sakai-Takemori, Yukiko, Oshima, Megumi, Nakagawa-Yoneda, Shiori, Ogura, Hisayuki, Sato, Koichi, Minami, Taichiro, Kitajima, Shinji, Toyama, Tadashi, Yamamura, Yuta, Miyagawa, Taro, Hara, Akinori, Shimizu, Miho, Furuichi, Kengo, Matsushima, Kouji, Wada, Takashi
• Format: Article
• Language: English
• Subjects: Animals; Bacterial Adhesion - drug effects; Biofilm; Biofilms - drug effects; Catheters - microbiology; D-serine; Disease Models, Animal; Down-Regulation - drug effects; Down-Regulation - genetics; Gene Expression Regulation, Bacterial - drug effects; Methicillin-Resistant Staphylococcus aureus - drug effects; Methicillin-Resistant Staphylococcus aureus - genetics; Methicillin-Resistant Staphylococcus aureus - physiology; Mice; Mice, Inbred BALB C; MRSA; Peritonitis - microbiology; Peritonitis - pathology; Polyvinyl Chloride; Serine - pharmacology
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2020.12.078

Although therapeutic agents for methicillin-resistant Staphylococcus aureus (MRSA) are clinically available, MRSA infection is still a life-threatening disease. Bacterial attachment and biofilm formation contribute significantly to the initiation of MRSA infection. Controlling MRSA’s attachment and biofilm formation might reduce the frequency of MRSA infection. According to recent data, some amino acids can reduce MRSA’s attachment on plates; however, their precise inhibitory mechanisms remain unclear. Therefore, we explored the effect of the amino acids on bacterial adhesion and biofilm formation in vitro and in vivo MRSA infection models. We tested the inhibitory effect of amino acids on MRSA and Escherichia coli (E. coli) in the attachment assay. Moreover, we evaluated the therapeutic potential of amino acids on the in vivo catheter infection model. Among the amino acids, D-Serine (D-Ser) was found to reduce MRSA’s ability to attach on plate assay. The proliferation of MRSA was not affected by the addition of D-Ser; thus, D-Ser likely only played a role in preventing attachment and biofilm formation. Then, we analyzed the expression of genes related to attachment and biofilm formation. D-Ser was found to reduce the expressions of AgrA, SarS, IcaA, DltD, and SdrD. Moreover, the polyvinyl chloride catheters treated with D-Ser had fewer MRSA colonies. D-Ser treatment also reduced the severity of infection in the catheter-induced peritonitis model. Moreover, D-Ser reduced the attachment ability of E. coli. D-Ser inhibits the attachment and biofilm formation of MRSA by reducing the expression of the related genes. Also, the administration of D-Ser reduces the severity of catheter infection in the mouse model. Therefore, D-Ser may be a promising therapeutic option for MRSA as well as E. coli infection. •D-Serine (D-Ser) was found to reduce methicillin-resistant Staphylococcus aureus (MRSA)’s ability to attach on the plate.•D-Ser reduced the expressions of the attachment related genes.•D-Ser treated polyvinyl chloride catheters showed less numbers of MRSA attachment.•D-Ser treatment also reduced the severity of infection in the catheter-induced peritonitis model.