Mucin O-glycans suppress quorum-sensing pathways and genetic transformation in Streptococcus mutans.

Mucus barriers accommodate trillions of microorganisms throughout the human body while preventing pathogenic colonization1. In the oral cavity, saliva containing the mucins MUC5B and MUC7 forms a pellicle that coats the soft tissue and teeth to prevent infection by oral pathogens, such as Streptococcus mutans2. Salivary mucin can interact directly with microorganisms through selective agglutinin activity and bacterial binding2-4, but the extent and basis of the protective functions of saliva are not well understood. Here, using an ex vivo saliva model, we identify that MUC5B is an inhibitor of microbial virulence. Specifically, we find that natively purified MUC5B downregulates the expression of quorum-sensing pathways activated by the competence stimulating peptide and the sigX-inducing peptide5. Furthermore, MUC5B prevents the acquisition of antimicrobial resistance through natural genetic transformation, a process that is activated through quorum sensing. Our data reveal that the effect of MUC5B is mediated by its associated O-linked glycans, which are potent suppressors of quorum sensing and genetic transformation, even when removed from the mucin backbone. Together, these results present mucin O-glycans as a host strategy for domesticating potentially pathogenic microorganisms without killing them.

Charge Influences Substrate Recognition and Self-Assembly of Hydrophobic FG Sequences.

The nuclear pore complex controls the passage of molecules via hydrophobic phenylalanine-glycine (FG) domains on nucleoporins. Such FG domains consist of repeating units of FxFG, FG, or GLFG sequences, many of which are interspersed with highly charged amino acid sequences. Despite the high density of charge in certain FG domains, if and how charge influences FG-domain self-assembly and selective binding of nuclear transport receptors is largely unexplored. Using rationally designed short peptide sequences, we determined that the charge type and identity of amino acids surrounding FG sequences impact the structure and selectivity of FG-based gels. Moreover, we showed that spatial localization of the charged amino acids with respect to the FG sequence determines the degree to which charge influences hydrophobic interactions. Taken together, our study highlights that charge type and placement of amino acids regulate FG-sequence function and are important considerations when studying the mechanism of nuclear pore complex transport in vivo.

Structure and expression of propanediol utilization microcompartments in Acetonema longum.

Numerous bacteria assemble proteinaceous microcompartments to isolate certain biochemical reactions within the cytoplasm. The assembly, structure, contents, and functions of these microcompartments are active areas of research. Here we show that the Gram-negative sporulating bacterium Acetonema longum synthesizes propanediol utilization (PDU) microcompartments when starved or grown on 1,2-propanediol (1,2-PD) or rhamnose. Electron cryotomography of intact cells revealed that PDU microcompartments are highly irregular in shape and size, similar to purified PDU microcompartments from Salmonella enterica serovar Typhimurium LT2 that were imaged previously. Homology searches identified a 20-gene operon in A. longum that contains most of the structural, enzymatic, and regulatory genes thought to be involved in PDU microcompartment assembly and function. Transcriptional data on PduU and PduC, which are major structural and enzymatic proteins, respectively, as well as imaging, indicate that PDU microcompartment synthesis is induced within 24 h of growth on 1,2-PD and after 48 h of growth on rhamnose.