期刊
NATURE MEDICINE
卷 21, 期 9, 页码 1091-+出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nm.3929
关键词
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资金
- Neurobiology Imaging Facility
- Neural Imaging Center as part of NINDS P30 Core Center grant [NS072030]
- NIH [1 S10 OD016401]
- BCH/PCMM
- US National Institutes of Health [PO1 AI1112521, RO1 AI111595, 5T32 HL066987]
- Ragon Institute at MGH
- EMBO Long-Term Fellowship [ALTF 251-2011]
- Human Frontiers Science Program [LT000079/2012]
- UNESCO L'Oreal National and International Women in Science Award
- Fulbright Award
- Weizmann Institute of Science-National Postdoctoral Award Program for Advancing Women in Science
- Cancer Research Institute Irvington Fellowship Program
- departmental Kirschstein-NRSA training grant
- Ragon Institute at MIT
- Ragon Institute at Harvard
- [U19AI095261]
The intestine is densely populated by anaerobic commensal bacteria. These microorganisms shape immune system development, but understanding of host-commensal interactions is hampered by a lack of tools for studying the anaerobic intestinal environment. We applied metabolic oligosaccharide engineering and bioorthogonal click chemistry to label various commensal anaerobes, including Bacteroides fragilis, a common and immunologically important commensal. We studied the dissemination of B. fragilis after acute peritonitis and characterized the interactions of the intact microbe and its polysaccharide components in myeloid and B cell lineages. We were able to assess the distribution and colonization of labeled B. fragilis along the intestine, as well as niche competition after coadministration of multiple species of the microbiota. We also fluorescently labeled nine additional commensals (eight anaerobic and one microaerophilic) from three phyla common in the gut-Bacteroidetes, Firmicutes and Proteobacteria-as well as one aerobic pathogen (Staphylococcus aureus). This strategy permits visualization of the anaerobic microbial niche by various methods, including intravital two-photon microscopy and non-invasive whole-body imaging, and can be used to study microbial colonization and host-microbe interactions in real time.
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