AUTHOR=Lin Yu-Chieh , Wu Chun-Yi , Huang Hung-Tse , Lu Mei-Kuang , Hu Wei-Shou , Lee Kung-Ta 

TITLE=Bacillus subtilis natto Derivatives Inhibit Enterococcal Biofilm Formation via Restructuring of the Cell Envelope

JOURNAL=Frontiers in Microbiology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2021.785351

DOI=10.3389/fmicb.2021.785351

ISSN=1664-302X

ABSTRACT=<p><italic>Enterococcus faecalis</italic> is considered a leading cause of hospital-acquired infections. Treatment of these infections has become a major challenge for clinicians because some <italic>E. faecalis</italic> strains are resistant to multiple clinically used antibiotics. Moreover, the presence of <italic>E. faecalis</italic> biofilms can make infections with <italic>E. faecalis</italic> more difficult to eradicate with current antibiotic therapies. Thus, our aim in this study was to investigate the effects of probiotic derivatives against <italic>E. faecalis</italic> biofilm formation. <italic>Bacillus subtilis</italic> natto is a probiotic strain isolated from Japanese fermented soybean foods, and its culture fluid potently inhibited adherence to Caco-2 cell monolayers, aggregation, and biofilm production without inhibiting the growth of <italic>E. faecalis</italic>. An apparent decrease in the thickness of <italic>E. faecalis</italic> biofilms was observed through confocal laser scanning microscopy. In addition, exopolysaccharide synthesis in <italic>E. faecalis</italic> biofilms was reduced by <italic>B. subtilis</italic> natto culture fluid treatment. Carbohydrate composition analysis also showed that carbohydrates in the <italic>E. faecalis</italic> cell envelope were restructured. Furthermore, transcriptome sequencing revealed that the culture fluid of <italic>B. subtilis</italic> natto downregulated the transcription of genes involved in the WalK/WalR two-component system, peptidoglycan biosynthesis and membrane glycolipid biosynthesis, which are all crucial for <italic>E. faecalis</italic> cell envelope synthesis and biofilm formation. Collectively, our work shows that some derivatives present in the culture fluid of <italic>B. subtilis</italic> natto may be useful for controlling <italic>E. faecalis</italic> biofilms.</p>