Streptococcus mutans Membrane Vesicles Harboring Glucosyltransferases Augment Candida albicans Biofilm Development

Abstract

<i>Candida albicans</i>, as the most common fungus in the oral cavity, is often detected in early childhood caries. <i>Streptococcus mutans</i> is the major etiological agent of dental caries, but the role of <i>S. mutans</i> on <i>C. albicans</i> growth and biofilm development remains to be elucidated. Membrane vesicles (MVs) are a cell-secreted subcellular fraction that play an important role in intercellular communication and disease progression. In the present study, we investigated whether MVs from <i>S. mutans</i> augment <i>C. albicans</i> growth and biofilm development. The results indicated that <i>S. mutans</i> MVs augmented <i>C. albicans</i> biofilm development but had no significant effect on <i>C. albicans</i> growth under planktonic conditions. Subsequently, we labeled <i>S. mutans</i> MVs with PKH26 and used confocal laser scanning microscopy (CLSM) to track <i>S. mutans</i> MVs, which were observed to be located in the <i>C. albicans</i> biofilm extracellular matrix. Monosaccharide tests showed that <i>S. mutans</i> MVs contribute to sucrose metabolism in <i>C. albicans</i>. Polysaccharides were significantly enriched in the <i>S. mutans</i> MV-treated group. MVs from Δ<i>gtfBC</i> mutant strains were compared with those from the wild-type <i>S. mutans.</i> The results revealed that MVs from the Δ<i>gtfBC</i> mutant had no effect on <i>C. albicans</i> biofilm formation and exopolysaccharide production. In addition, <i>C. albicans</i> biofilm transcriptional regulators (<i>Ndt80</i>, <i>Als1</i>, <i>Mnn9</i>, <i>Van1</i>, <i>Pmr1</i>, <i>Gca1</i>, and <i>Big1</i>) expression were upregulated in <i>S. mutans</i> MV-treated group. In summary, the results of the present study showed that <i>S. mutans</i> MVs harboring glucosyltransferases involved in exopolysaccharide production augment <i>C. albicans</i> biofilm development, revealing a key role for <i>S. mutans</i> MVs in cross-kingdom interactions between <i>S. mutans</i> and <i>C. albicans</i>.