Anything You Can Do I Can Do Better: Divergent Mechanisms to Metabolize Milk Oligosaccharides by Two Bifidobacterial Species. David A.

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1 Anything You Can Do I Can Do Better: Divergent Mechanisms to Metabolize Milk Oligosaccharides by Two Bifidobacterial Species David A. Sela IMGC 2013

2 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

3 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

4 Microbial symbionts profoundly influence their host Insect intracellular symbiont Rickettsia Complements nutritional requirements for the host Jeffrey Gordon, Washington University SOM, St. Louis

5 Milk bioactives Glycopeptides Lactoferrin Secretory IgA Lysozyme Lipids Fat & water soluble vitamins Carbohydrates Pierre Holtz for UNICEF Infant Health

6 Milk bioactives Pierre Holtz for UNICEF Infant Development & Health Microbial symbionts

7 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

8 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

9 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

10 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

11 B. bifidum extracellularly processes HMO prior to import B. bifidum B. infantis Asakuma S et al. J. Biol. Chem B. bifidum ignores fucose- extracellular fucosidase

12 Do bifidobacterial transcriptomes vary when consuming different HMO species? COMING SOON

13 B. infantis transcriptome varies by oligosaccharide COMING SOON

14 The B. bifidum transcriptome reflects its alternative HMO strategy COMING SOON

15 Pooled HMO and single species transcriptomes cluster in infantis COMING SOON

16 Transcriptomes cluster differently in B. bifidum COMING SOON

17 Pairwise correlations of all infantis and bifidum transcriptomes COMING SOON

18 COMING SOON

19 Is this surprising given that it is a primary mucin consumer? Turroni, et al, PNAS 2010 B. bifidum consumes mucin!

20 Take home COMING SOON

21 Acknowledgements Daniel Garrido Danielle Lemay Bruce German David Mills Others at FFHI & UCD

22 Questions? selalab.org

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