MdpS and MdpS2 structurally and functionally diverge to regulate Streptococcus oralis mucin degradation

The human oral cavity harbors a diverse microbial community, with oral streptococci, particularly the Streptococcus mitis group, playing a pivotal role in biofilm formation and oral health. Among these, Streptococcus oralis is a key early colonizer that stabilizes oral biofilms. Here, we identify two mucin-degrading proteases, MdpS and MdpS2, that enable S. oralis to degrade MUC5B, the sole gel-forming mucin in saliva. Despite low sequence similarity, these enzymes share a high degree of tertiary structural resemblance and exhibits complementary biological functions. Their activity leads to extensive MUC5B degradation influencing biofilm dynamics by promoting biofilm dispersal and altering MUC5B and/or MUC5AC BCi mucus gels properties, with MdpS2 displaying specificity for MUC5B gels. Our findings reveal a specialized role in biofilm structural remodeling, offering potential avenues for clinical applications in biofilm modulation and mucus degradation.