Anything You Can Do I Can Do Better: Divergent Mechanisms to Metabolize Milk Oligosaccharides by Two Bifidobacterial Species David A. Sela IMGC 2013
This is not our planet Bacteria present by 3.9 bya Archaea and Eukaryota by >2 bya Animals appear ~1 bya The platypus diverged from other mammals 180 mya Mammals have evolved in a global bioreactor! Mammals have evolved a codependence on microbes, some of which are essential for normal development and host physiology
Microbial symbionts profoundly influence their host Insect intracellular symbiont Rickettsia Complements nutritional requirements for the host Participates in reproductive manipulation of its insect host- parthenogenesis
Microbial symbionts profoundly influence their host Insect intracellular symbiont Rickettsia Complements nutritional requirements for the host Jeffrey Gordon, Washington University SOM, St. Louis
Milk bioactives Glycopeptides Lactoferrin Secretory IgA Lysozyme Lipids Fat & water soluble vitamins Carbohydrates Pierre Holtz for UNICEF Infant Health
Milk bioactives Pierre Holtz for UNICEF Infant Development & Health Microbial symbionts
Breast milk molds the composition of GIT microbial consortium B. infantis Enrichment in Bifidobacterium sp. and decrease in other taxa Often most abundant genus in the first year of life, across several geographies FF Formula-fed infants do not share this feature Infant-gut associated bifidobacteria BF Yatsunenko, Nature 2012 B. longum subsp. infantis B. longum subsp. longum B. breve B. bifidum
Bifidobacteria are thought to benefit the developing neonate Promote butyrogenesis Acetate has local activity against EHEC Competitive exclusion Ameliorate infections Reinforce tight junctions Anti-inflammatory activity
B. infantis and B. bifidum capture milk glycans through divergent means Genome sequence suggests: Sela, DA, and Mills, DA. Trends in microbiology (2010) infantis- imports intact HMO molecules bifidum- imports some HMO degradation products Please see: Ruiz-Moyano, S., AEM 2013
Ecological distribution of dominant bifidobacteria is age dependent Infants: B. longum (infantis)- 56.2% B. bifidum- 10.7% Mother: B. longum (infantis)- 38.2% B. adolescentis- 20.3% Difficult to discriminate infantis from longum! Turroni F, et al, PLOS ONE 2012
B. bifidum extracellularly processes HMO prior to import B. bifidum B. infantis Asakuma S et al. J. Biol. Chem. 2011 B. bifidum ignores fucose- extracellular fucosidase
Do bifidobacterial transcriptomes vary when consuming different HMO species? COMING SOON
B. infantis transcriptome varies by oligosaccharide COMING SOON
The B. bifidum transcriptome reflects its alternative HMO strategy COMING SOON
Pooled HMO and single species transcriptomes cluster in infantis COMING SOON
Transcriptomes cluster differently in B. bifidum COMING SOON
Pairwise correlations of all infantis and bifidum transcriptomes COMING SOON
COMING SOON
Is this surprising given that it is a primary mucin consumer? Turroni, et al, PNAS 2010 B. bifidum consumes mucin!
Take home COMING SOON
Acknowledgements Daniel Garrido Danielle Lemay Bruce German David Mills Others at FFHI & UCD
Questions? selalab.org davidsela@umass.edu