Identification of Allobaculum mucolyticum as a novel human intestinal mucin degrader

被引:120
作者
van Muijlwijk, Guus H. [1 ]
van Mierlo, Guido [2 ,5 ]
Jansen, Pascal W. T. C. [2 ]
Vermeulen, Michiel [2 ]
Bleumink-Pluym, Nancy M. C. [3 ]
Palm, Noah W. [4 ]
van Putten, Jos P. M. [3 ]
de Zoete, Marcel R. [1 ]
机构
[1] Univ Med Ctr Utrecht, Dept Med Microbiol, Utrecht, Netherlands
[2] Radboud Univ Nijmegen, Fac Sci, Radboud Inst Mol Life Sci, Oncode Inst,Dept Mol Biol, Nijmegen, Netherlands
[3] Univ Utrecht, Dept Biomol Hlth Sci, Utrecht, Netherlands
[4] Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT USA
[5] Ecole Polytech Fed Lausanne EPFL, Sch Life Sci, Inst Bioengn, Lab Syst Biol & Genet, CH-1015 Lausanne, Switzerland
关键词
Allobaculum mucolyticum; microbiota; intestinal mucin; mucin o-glycans; mucin degradation; cazymes; glycosidase; pathobiont; proteome; GUT MICROBIOTA; GEN.-NOV; PATHOGEN; BACTERIA;
D O I
10.1080/19490976.2021.1966278
中图分类号
R57 [消化系及腹部疾病];
学科分类号
100201 [内科学];
摘要
The human gut microbiota plays a central role in intestinal health and disease. Yet, many of its bacterial constituents are functionally still largely unexplored. A crucial prerequisite for bacterial survival and proliferation is the creation and/or exploitation of an own niche. For many bacterial species that are linked to human disease, the inner mucus layer was found to be an important niche. Allobaculum mucolyticum is a newly identified, IBD-associated species that is thought be closely associated with the host epithelium. To explore how this bacterium is able to effectively colonize this niche, we screened its genome for factors that may contribute to mucosal colonization. Up to 60 genes encoding putative Carbohydrate Active Enzymes (CAZymes) were identified in the genome of A. mucolyticum. Mass spectrometry revealed 49 CAZymes of which 26 were significantly enriched in its secretome. Functional assays demonstrated the presence of CAZyme activity in A. mucolyticum conditioned medium, degradation of human mucin O-glycans, and utilization of liberated non-terminal monosaccharides for bacterial growth. The results support a model in which sialidases and fucosidases remove terminal O-glycan sugars enabling subsequent degradation and utilization of carbohydrates for A. mucolyticum growth. A. mucolyticum CAZyme secretion may thus facilitate bacterial colonization and degradation of the mucus layer and may pose an interesting target for future therapeutic intervention.
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