Abstract
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 binding2,3,4, 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.
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Data availability
The high-throughput sequencing data presented in Figs. 1 and 2 are deposited at the Gene Expression Omnibus under accession number GSE163258. All other data are available from the corresponding author on reasonable request. Source data are provided with this paper.
Code availability
Code used for transcriptional analysis is available at GitHub (https://github.com/cwerlang/Smutans-MUC5B-RNASeq).
References
Hansson, G. C. Mucins and the microbiome. Annu. Rev. Biochem. 89, 769–793 (2020).
Cross, B. W. & Ruhl, S. Glycan recognition at the saliva—oral microbiome interface. Cell. Immunol. 333, 19–33 (2018).
Tabak, L. A. In defense of the oral cavity: structure, biosynthesis, and function of salivary mucins. Annu. Rev. Physiol. 57, 547–564 (1995).
Deng, L. et al. Oral streptococci utilize a Siglec-like domain of serine-rich repeat adhesins to preferentially target platelet sialoglycans in human blood. PLoS Pathog. 10, e1004540 (2014).
Shanker, E. & Federle, M. J. Quorum sensing regulation of competence and bacteriocins in Streptococcus pneumoniae and mutans. Genes 8, 15 (2017).
Nakano, K., Nomura, R. & Ooshima, T. Streptococcus mutans and cardiovascular diseases. Jpn. Dent. Sci. Rev. 44, 29–37 (2008).
Murchison, H. H., Barrett, J. F., Cardineau, G. A. & Curtiss, R. Transformation of Streptococcus mutans with chromosomal and shuttle plasmid (pYA629) DNAs. Infect. Immun. 54, 273–282 (1986).
Villedieu, A. et al. Prevalence of tetracycline resistance genes in oral bacteria. Antimicrob. Agents Chemother. 47, 878–882 (2003).
Chansley, P. E. & Kral, T. A. Transformation of fluoride resistance genes in Streptococcus mutans. Infect. Immun. 57, 1968–1970 (1989).
Hernando-Amado, S., Coque, T. M., Baquero, F. & Martínez, J. L. Defining and combating antibiotic resistance from one health and global health perspectives. Nat. Microbiol. 4, 1432–1442 (2019).
Villedieu, A. et al. Genetic basis of erythromycin resistance in oral bacteria. Antimicrob. Agents Chemother. 48, 2298–2301 (2004).
Olsen, I., Tribble, G. D., Fiehn, N.-E. & Wang, B.-Y. Bacterial sex in dental plaque. J. Oral Microbiol. 5, 20736 (2013).
Loesche, W. J. Role of Streptococcus mutans in human dental decay. Microbiol. Rev. 50, 353–380 (1986).
Loesche, W. J., Rowan, J., Straffon, L. H. & Loos, P. J. Association of Streptococcus mutans with human dental decay. Infect. Immun. 11, 1252–1260 (1975).
Mathews, S. A., Kurien, B. T. & Scofield, R. H. Oral manifestations of Sjögren’s syndrome. J. Dent. Res. 87, 308–318 (2008).
Pramanik, R., Osailan, S. M., Challacombe, S. J., Urquhart, D. & Proctor, G. B. Protein and mucin retention on oral mucosal surfaces in dry mouth patients. Eur. J. Oral. Sci. 118, 245–253 (2010).
Frenkel, E. S. & Ribbeck, K. Salivary mucins in host defense and disease prevention. J. Oral Microbiol. 7, 29759 (2015).
Ahn, S.-J., Wen, Z. T. & Burne, R. A. Multilevel control of competence development and stress tolerance in Streptococcus mutans UA159. Infect. Immun. 74, 1631–1642 (2006).
Ahn, S.-J., Ahn, S.-J., Wen, Z. T., Brady, L. J. & Burne, R. A. Characteristics of biofilm formation by Streptococcus mutans in the presence of saliva. Infect. Immun. 76, 4259–4268 (2008).
Duarte, S. et al. Influences of starch and sucrose on Streptococcus mutans biofilms. Oral Microbiol. Immunol. 23, 206–212 (2008).
Mitchell, T. J. The pathogenesis of streptococcal infections: from tooth decay to meningitis. Nat. Rev. Microbiol. 1, 219–230 (2003).
Frenkel, E. S. & Ribbeck, K. Salivary mucins protect surfaces from colonization by cariogenic bacteria. Appl. Environ. Microbiol. 81, 332–338 (2015).
Frenkel, E. S. & Ribbeck, K. Salivary mucins promote the coexistence of competing oral bacterial species. ISME J. 11, 1286–1290 (2017).
Levine, M. Salivary proteins may be useful for determining caries susceptibility. J. Evid. Based Dent. Pract. 13, 91–93 (2013).
Thomsson, K. A., Schulz, B. L., Packer, N. H. & Karlsson, N. G. MUC5B glycosylation in human saliva reflects blood group and secretor status. Glycobiology 15, 791–804 (2005).
Ajdic, D. et al. Genome sequence of Streptococcus mutans UA159, a cariogenic dental pathogen. Proc. Natl Acad. Sci. USA 99, 14434–14439 (2002).
Paik, S., Brown, A., Munro, C. L., Cornelissen, C. N. & Kitten, T. The sloABCR operon of Streptococcus mutans encodes an Mn and Fe transport system required for endocarditis virulence and its Mn-dependent repressor. J. Bacteriol. 185, 5967–5975 (2003).
Nicolas, G. G. Detection of putative new mutacins by bioinformatic analysis using available web tools. BioData Min. 4, 22 (2011).
Aframian, N. & Eldar, A. A bacterial tower of Babel: quorum-sensing signaling diversity and its evolution. Annu. Rev. Microbiol. 74, 587–606 (2020).
Merritt, J., Qi, F. & Shi, W. A unique nine-gene comY operon in Streptococcus mutans. Microbiology 151, 157–166 (2005).
Underhill, S. A. M. et al. Intracellular signaling by the comRS system in Streptococcus mutans genetic competence. mSphere 3, e00444-18 (2018).
Dufour, D., Cordova, M., Cvitkovitch, D. G. & Lévesque, C. M. Regulation of the competence pathway as a novel role associated with a streptococcal bacteriocin. J. Bacteriol. 193, 6552–6559 (2011).
Hossain, M. S. & Biswas, I. Mutacins from Streptococcus mutans UA159 are active against multiple streptococcal species. Appl. Environ. Microbiol. 77, 2428–2434 (2011).
Merritt, J. & Qi, F. The mutacins of Streptococcus mutans: regulation and ecology. Mol. Oral. Microbiol 27, 57–69 (2012).
Son, M., Shields, R. C., Ahn, S. J., Burne, R. A. & Hagen, S. J. Bidirectional signaling in the competence regulatory pathway of Streptococcus mutans. FEMS Microbiol. Lett. 362, fnv159 (2015).
Reck, M., Tomasch, J. & Wagner-Döbler, I. The alternative sigma factor SigX controls bacteriocin synthesis and competence, the two quorum sensing regulated traits in Streptococcus mutans. PLoS Genet. 11, e1005353 (2015).
Perry, J. A., Cvitkovitch, D. G. & Lévesque, C. M. Cell death in Streptococcus mutans biofilms: a link between CSP and extracellular DNA. FEMS Microbiol. Lett. 299, 261–266 (2009).
Wenderska, I. B. et al. A novel function for the competence inducing peptide, XIP, as a cell death effector of Streptococcus mutans. FEMS Microbiol. Lett. 336, 104–112 (2012).
Perry, D. & Kuramitsu, H. K. Genetic transformation of Streptococcus mutans. Infect. Immun. 32, 1295–1297 (1981).
Desai, K., Mashburn-Warren, L., Federle, M. J. & Morrison, D. A. Development of competence for genetic transformation of Streptococcus mutans in a chemically defined medium. J. Bacteriol. 194, 3774–3780 (2012).
Khan, R. et al. Extracellular identification of a processed type II ComR/ComS pheromone of Streptococcus mutans. J. Bacteriol. 194, 3781–3788 (2012).
Khan, R. et al. A positive feedback loop mediated by Sigma X enhances expression of the streptococcal regulator ComR. Sci. Rep. 7, 5984 (2017).
Nakano, K. et al. Streptococcus mutans clonal variation revealed by multilocus sequence typing. J. Clin. Microbiol. 45, 2616–2625 (2007).
Mukherjee, S. & Bassler, B. L. Bacterial quorum sensing in complex and dynamically changing environments. Nat. Rev. Microbiol. https://doi.org/10.1038/s41579-019-0186-5 (2019).
Visch, L. L., Gravenmade, E. J., Schaub, R. M., Van Putten, W. L. & Vissink, A. A double-blind crossover trial of CMC- and mucin-containing saliva substitutes. Int. J. Oral Max. Surg. 15, 395–400 (1986).
Silverman, H. S. et al. In vivo glycosylation of mucin tandem repeats. Glycobiology 11, 459–471 (2001).
Zalewska, A., Zwierz, K., Zółkowski, K. & Gindzieński, A. Structure and biosynthesis of human salivary mucins. Acta Biochim. Pol. 47, 1067–1079 (2000).
Wheeler, K. M. et al. Mucin glycans attenuate the virulence of Pseudomonas aeruginosa in infection. Nat. Microbiol. 4, 2146–2154 (2019).
Werlang, C., Cárcarmo-Oyarce, G. & Ribbeck, K. Engineering mucus to study and influence the microbiome. Nat. Rev. Mater. https://doi.org/10.1038/s41578-018-0079-7 (2019).
Wang, B. X. et al. Mucin glycans signal through the sensor kinase RetS to inhibit virulence-associated traits in Pseudomonas aeruginosa. Curr. Biol. 31, 90–102 (2021).
Huang, Y., Mechref, Y. & Novotny, M. V. Microscale nonreductive release of O-Linked glycans for subsequent analysis through MALDI mass spectrometry and capillary electrophoresis. Anal. Chem. 73, 6063–6069 (2001).
Khan, R. et al. Comprehensive transcriptome profiles of Streptococcus mutans UA159 map core streptococcal competence genes. mSystems 1, e00038 (2016).
Rayment, S. A., Liu, B., Offner, G. D., Oppenheim, F. G. & Troxler, R. F. Immunoquantification of human salivary mucins MG1 and MG2 in stimulated whole saliva: factors influencing mucin levels. J. Dent. Res. 79, 1765–1772 (2000).
Son, M., Ahn, S.-J., Guo, Q., Burne, R. A. & Hagen, S. J. Microfluidic study of competence regulation in Streptococcus mutans: environmental inputs modulate bimodal and unimodal expression of comX. Mol. Microbiol. 86, 258–272 (2012).
Ricomini Filho, A. P., Khan, R., Åmdal, H. A. & Petersen, F. C. Conserved pheromone production, response and degradation by Streptococcus mutans. Front. Microbiol. 10, 2140 (2019).
Hagen, S. J. & Son, M. Origins of heterogeneity in Streptococcus mutans competence: interpreting an environment-sensitive signaling pathway. Phys. Biol. 14, 015001 (2017).
Hillman, J. D., Mo, J., McDonell, E., Cvitkovitch, D. & Hillman, C. H. Modification of an effector strain for replacement therapy of dental caries to enable clinical safety trials. J. Appl. Microbiol. 102, 1209–1219 (2007).
Singla, D., Sharma, A., Sachdev, V. & Chopra, R. Distribution of Streptococcus mutans and Streptococcus sobrinus in dental plaque of indian pre-school children using PCR and SB-20M agar medium. J. Clin. Diagn. Res. 10, ZC60–ZC63 (2016).
Rodriguez, A. M. et al. Physiological and molecular characterization of genetic competence in Streptococcus sanguinis. Mol. Oral Microbiol. 26, 99–116 (2011).
Darch, S. E. et al. Spatial determinants of quorum signaling in a Pseudomonas aeruginosa infection model. Proc. Natl Acad. Sci. USA 115, 4779–4784 (2018).
Wu, C. et al. Regulation of ciaXRH operon expression and identification of the CiaR regulon in Streptococcus mutans. J. Bacteriol. 192, 4669–4679 (2010).
Qi, F., Merritt, J., Lux, R. & Shi, W. Inactivation of the ciaH gene in Streptococcus mutans diminishes mutacin production and competence development, alters sucrose-dependent biofilm formation, and reduces stress tolerance. Infect. Immun. 72, 4895–4899 (2004).
Biswas, S. & Biswas, I. Role of HtrA in surface protein expression and biofilm formation by Streptococcus mutans. Infect. Immun. 73, 6923–6934 (2005).
Senadheera, M. D. et al. A VicRK signal transduction system in Streptococcus mutans affects gtfBCD, gbpB, and ftf expression, biofilm formation, and genetic competence development. J. Bacteriol. 187, 4064–4076 (2005).
Domenech, A. et al. Proton motive force disruptors block bacterial competence and horizontal gene transfer. Cell Host Microbe 27, 544–555 (2020).
Merritt, J., Zheng, L., Shi, W. & Qi, F. Genetic characterization of the hdrRM operon: a novel high-cell-density-responsive regulator in Streptococcus mutans. Microbiology 153, 2765–2773 (2007).
Okinaga, T., Niu, G., Xie, Z., Qi, F. & Merritt, J. The hdrRM operon of Streptococcus mutans encodes a novel regulatory system for coordinated competence development and bacteriocin production. J. Bacteriol. 192, 1844–1852 (2010).
Alves, L. A. et al. PepO is a target of the two-component systems VicRK and CovR required for systemic virulence of Streptococcus mutans. Virulence 11, 521–536 (2020).
Underhill, S. A. M., Shields, R. C., Burne, R. A. & Hagen, S. J. Carbohydrate and PepO control bimodality in competence development by Streptococcus mutans. Mol. Microbiol. 112, 1388–1402 (2019).
Kaspar, J. R., Lee, K., Richard, B., Walker, A. R. & Burne, R. A. Direct interactions with commensal streptococci modify intercellular communication behaviors of Streptococcus mutans. ISME J. https://doi.org/10.1038/s41396-020-00789-7 (2020).
Idone, V. et al. Effect of an orphan response regulator on Streptococcus mutans sucrose-dependent adherence and cariogenesis. Infect. Immun. 71, 4351–4360 (2003).
Nagasawa, R., Sato, T. & Senpuku, H. Raffinose induces biofilm formation by Streptococcus mutans in low concentrations of sucrose by increasing production of extracellular DNA and fructan. Appl. Environ. Microbiol. 83, e00869 (2017).
Suzuki, Y., Nagasawa, R. & Senpuku, H. Inhibiting effects of fructanase on competence-stimulating peptide-dependent quorum sensing system in Streptococcus mutans. J. Infect. Chemother. 23, 634–641 (2017).
Yoshida, A., Ansai, T., Takehara, T. & Kuramitsu, H. K. LuxS-based signaling affects Streptococcus mutans biofilm formation. Appl. Environ. Microbiol. 71, 2372–2380 (2005).
Son, M., Ghoreishi, D., Ahn, S.-J., Burne, R. A. & Hagen, S. J. Sharply tuned pH response of genetic competence regulation in Streptococcus mutans: a microfluidic study of the environmental sensitivity of comX. Appl. Environ. Microbiol. 81, 5622–5631 (2015).
Nielsen, S. S. in Food Analysis Laboratory Manual 137–141 (Springer, 2017).
Aoki, K. et al. The diversity of O-linked glycans expressed during Drosophila melanogaster development reflects stage- and tissue-specific requirements for cell signaling. J. Biol. Chem. 283, 30385–30400 (2008).
Kumagai, T., Katoh, T., Nix, D. B., Tiemeyer, M. & Aoki, K. In-gel β-elimination and aqueous-organic partition for improved O- and sulfoglycomics. Anal. Chem. 85, 8692–8699 (2013).
Anumula, K. R. & Taylor, P. B. A comprehensive procedure for preparation of partially methylated alditol acetates from glycoprotein carbohydrates. Anal. Biochem. 203, 101–108 (1992).
Liu, Y. et al. The minimum information required for a glycomics experiment (MIRAGE) project: improving the standards for reporting glycan microarray-based data. Glycobiology 27, 280–284 (2017).
Clark, K., Karsch-Mizrachi, I., Lipman, D. J., Ostell, J. & Sayers, E. W. GenBank. Nucleic Acids Res. 44, D67–D72 (2016).
O’Leary, N. A. et al. Reference sequence (RefSeq) database at NCBI: current status, taxonomic expansion, and functional annotation. Nucleic Acids Res. 44, D733–D745 (2016).
Afgan, E. et al. The Galaxy platform for accessible, reproducible and collaborative biomedical analyses: 2018 update. Nucleic Acids Res. 46, W537–W544 (2018).
Huber, W. et al. Orchestrating high-throughput genomic analysis with Bioconductor. Nat. Methods 12, 115–121 (2015).
Anders, S. & Huber, W. Differential expression analysis for sequence count data. Genome Biol. 11, R106 (2010).
Kanehisa, M., Sato, Y., Kawashima, M., Furumichi, M. & Tanabe, M. KEGG as a reference resource for gene and protein annotation. Nucleic Acids Res. 44, D457–D462 (2016).
Thissen, D., Steinberg, L. & Kuang, D. Quick and easy implementation of the Benjamini–Hochberg procedure for controlling the false positive rate in multiple comparisons. J. Educ. Behav. Stat. 27, 77–83 (2002).
Aymanns, S., Mauerer, S., Zandbergen, G., Wolz, C. & Spellerberg, B. High-level fluorescence labeling of Gram-positive pathogens. PLoS ONE 6, e19822 (2011).
Takehara, S., Yanagishita, M., Podyma-Inoue, K. A. & Kawaguchi, Y. Degradation of MUC7 and MUC5B in human saliva. PLoS ONE 8, e69059 (2013).
Acknowledgements
We thank S. Underhill, S. Hagen, S.-J. Ahn and R. Burne for sharing several genetically modified S. mutans UA159 strains; B. Spellerberg for sharing the PBSU101 plasmid; the staff at the Koch Institute Swanson Biotechnology Center for technical support, specifically A. Leshinsky and H. Amoroso in the Biopolymers and Proteomics core; the staff at the MIT BioMicro Center for technical support, especially S. Levine, N. Kamelamela and A. Stortchevoi; and E. S. Frenkel, B. Turner, B. Wang, C. Wu and the entire Ribbeck group at MIT for discussions. We acknowledge funding support from the MIT Deshpande Center, NIBIB/NIH (no. R01-EB017755), NSF CAREER (no. 1454673), NIH Common Fund (no. U01GM125267), the Amgen Scholars Program, the National Institute of Environmental Health Sciences of the NIH (no. P30-ES002109), the NSF MRSEC Program (no. DMR-14-19807), the US Army Research Office under cooperative agreement W911NF-19-2-0026 for the Institute for Collaborative Biotechnologies, the NSF Graduate Research Fellowship Program (no.1122374) and the NIGMS/NIH Interdepartmental Biotechnology Training Program (no. T32 GM008334).
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C.A.W., W.G.C. and K.M.W. generated mucin-related biochemical reagents and protocols. K.A. performed MS analysis. C.A.W., W.G.C., C.T., C.J.M., A.C.B. and K.K. performed transformation and biofilm formation experiments and developed related protocols. C.A.W. isolated RNA and analysed gene expression data. M.T. and K.R. supervised the study. All of the authors contributed to writing and reviewing the manuscript.
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Extended data
Extended Data Fig. 1 MUC5AC glycan pools are highly similar to MUC5B glycan pools in composition and effects on S. mutans gene expression and phenotypes.
MUC5AC glycans were isolated from comercially available pig gastric mucin (Millipore Sigma) using beta-elimination51. MUC5AC was purified from pig stomachs as described previously48,50. Sigma PGM is pig gastric mucin purchased from Millipore Sigma that has been dialysed (100 kDa cut-off) and lyophilized. a, A comparison on the most abundant glycan structures (at least 1% of the pool) in MUC5B and MUC5AC (n = 1). b, MUC5AC glycans are relatively enriched for O-GalNAc core-2 structures and display less fucose than MUC5B. c, RNA-Seq was used to profile the effects of 0.1% MUC5AC glycans on gene expression in S. mutans in parallel with studies on MUC5B mucin and MUC5B glycans (n = 2). d, The expression profiles of MUC5B glycans and MUC5AC glycans have a Pearson’s correlation coefficient of 0.93, indicating that they induce highly similar changes in S. mutans global gene expression. e, MUC5AC glycans have a concentration-dependent influence on comS expression. Nonlinear antagonist binding best-fit curves shown (IC50 = 0.05, HillSlope = -6.5, R2 = 0.51). f, RT-qPCR evaluation of S. mutans gene expression after 2 hours incubation in CM with 0.1 wt% of each supplement. We see that all mucins and mucin glycans downregulate the expression of key quorum sensing genes (n > 4, for full data see Source Data). Interestingly, released mucin glycans (both MUC5B and MUC5AC) have stronger effects than intact mucin proteins (MUC5B and MUC5AC polymers). g, Mucins (MUC5B and MUC5AC) and mucin glycans (MUC5B and MUC5AC) reduce transformation frequency of S. mutans at 0.1 wt% in CMedia. While MUC5AC glycans reduce biofilm formation at 0.1 wt% in CMedia, MUC5B glycans did not. h, Growth profiles in CMedia are not altered when supplemented with 0.1 wt% of various monosaccharides. KEY: pig gastric mucin (PGM), N-acetylgalactosamine (GalNAc), N-acetylglucosamine (GlcNAc), and N-acetylneuraminic acid (Neu5Ac). *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001, NS = not significant. For f, data are means, and significance was assessed using unpaired t tests with the Benjamini-Hochberg correction87. For g, data are geometric means ± geometric standard deviations, and significance was assessed using the Kruskal-Wallis test followed by an uncorrected Dunn’s test, which does not assume a Gaussian distribution.
Extended Data Fig. 2 MUC5B reduces transformation and biofilm formation of S. mutans across various media conditions.
a, MUC5B reduces transformation frequency in multiple media conditions: CM (25%Todd-Hewitt), 100%Todd-Hewitt, 100%Todd-Hewitt + 5% Bacto Yeast Extract. b, MUC5B reduces transformation rates in CM with or without 1% sucrose supplementation to promote biofilm formation. c, MUC5B prevents biofilm formation in CM with and without 1% sucrose supplementation, as observed previously22. d, MUC5B reduces transformation efficiency in CM supplemented with 1-10 μM CSP. e, MUC5B reduces transformation in DM supplemented with XIP and (f) CM supplemented with XIP. XIP is less effective at inducing competence in CM compared to DM. *P < 0.05, **P < 0.01. Data are geometric mean ± geometric standard deviation, and significance was assessed using nonparametric Mann-Whitney tests.
Extended Data Fig. 3 MUC5B reduces transformation rates in ΔcomC, ΔcomE, and ΔcomS strains.
a, S. mutans UA159 ΔcomC, ΔcomDE, and ΔcomE18 have natural transformation rates similar to wildtype, and supplementation with 1 μM CSP does not alter transformation rates in ΔcomE. MUC5B is able to induce the same reduction of transformation rates in ΔcomC and ΔcomE strains as in the wildtype, with and without supplemental CSP. b, We confirm that the ΔcomS31 strain was not transformable. However, when supplemented with 10 μM XIP, the ΔcomS knockout shows transformation rates similar to wildtype. Here, we see that MUC5B mucin and MUC5AC glycans reduce transformation rates in the ΔcomS knockout supplemented with 10 μM XIP. *P < 0.05, **P < 0.01, ***P < 0.001, NS = not significant, ND = not detected. Data are geometric means ± geometric standard deviations, and significance was assessed using nonparametric Mann-Whitney tests.
Extended Data Fig. 4 MUC5B prevents biofilm formation and transformation in multiple Streptococcus mutans strains.
a, MUC5B reduces biofilm formation of multiple strains of S. mutans (UA159, SJ, and 28BE3) in CM. MUC5B has no significant effect on biofilm formation of S. sobrinus 6715 (S. sob). b, MUC5B reduces transformation of S. mutans strain 28BE3 in CM. **P < 0.01, NS = not significant. Data are geometric means ± geometric standard deviations, and significance was assessed using nonparametric Mann-Whitney tests.
Supplementary information
Supplementary Information
Supplementary Table 3 and Figs. 1 and 2.
Supplementary Table 1
Transcriptional analysis of samples treated with 0.1% MUC5B mucin, 0.1% MUC5B glycans and 0.1% MUC5AC glycans.
Supplementary Table 2
Pathway enrichment analysis.
Source data
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Werlang, C.A., Chen, W.G., Aoki, K. et al. Mucin O-glycans suppress quorum-sensing pathways and genetic transformation in Streptococcus mutans. Nat Microbiol 6, 574–583 (2021). https://doi.org/10.1038/s41564-021-00876-1
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DOI: https://doi.org/10.1038/s41564-021-00876-1
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