Xylitol Inhibits Growth and Blocks Virulence in Serratia marcescens

Abstract

<i>Serratia marcescens</i> is an opportunistic nosocomial pathogen and causes wound and burn infections. It shows high resistance to antibiotics and its pathogenicity is mediated by an arsenal of virulence factors. Another therapeutic option to such infections is targeting quorum sensing (QS), which controls the expression of different <i>S. marcescens</i> virulence factors. Prevention of QS can deprive <i>S. marcescens</i> from its bacterial virulence without applying stress on the bacterial growth and facilitates the eradication of the bacteria by immunity. The objective of the current study is to explore the antimicrobial and antivirulence activities of xylitol against <i>S. marcescens</i>. Xylitol could inhibit the growth of <i>S. marcescens</i>. Sub-inhibitory concentrations of xylitol could inhibit biofilm formation, reduce prodigiosin production, and completely block protease activity. Moreover, xylitol decreased swimming motility, swarming motility and increased the sensitivity to hydrogen peroxide. The expression of <i>rsmA</i>, <i>pigP</i>, <i>flhC</i>, <i>flhD fimA</i>, fimC, <i>shlA bsmB</i>, and <i>rssB</i> genes that regulate virulence factor production was significantly downregulated by xylitol. In silico study showed that xylitol could bind with the SmaR receptor by hydrophobic interaction and hydrogen bonding, and interfere with the binding of the natural ligand with SmaR receptor. An in vivo mice survival test confirmed the ability of xylitol to protect mice against the virulence of <i>S. marcescens</i>. In conclusion, xylitol is a growth and virulence inhibitor in <i>S. marcescens</i> and can be employed for the treatment of <i>S. marcescens</i> wound and burn infections.