beiko smbe2013-final
TRANSCRIPT
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. . .Conor
Meehan
& Rob Beiko
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Meet the LachnospiraceaeBryant and Small, 1956
fao.org
Wooly Coil+
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Meet the Lachnospiraceae
Bacteria
Archaea
Pigeon:Fir0002/Flagstaffotos (Wikimedia Commons)
Things that are made of cells
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Meet the Lachnospiraceae
Firmicutes
Proteobacteria
Domain Bacteria
ActinobacteriaBacteroidetetetes
Cyanobacteria
Interesting weirdos(Aquificae, Thermotogae, Nitrospirae,Syergistetes, Elusimicrobia, TM7, TMZ,OP6, and so on)
Acidobacteria (maybe)
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Meet the Lachnospiraceae
Clostridia
Phylum Firmicutes(aka, Low-G+C Gram-positives)
Negativicutes
Erysipelotrichia
Thermolithobacteria
Bacilli
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Meet the Lachnospiraceae
Clostridiales
Class Clostridia
Natranaerobiales
Thermoanaerobacterales
Halanaerobiales
Bathrobiales
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Meet the Lachnospiraceae
Lachnospiraceae
Order Clostridiales
CaldicoprobacteraceaeCatabacteriaceae
Ruminococcaceae
ClostridiaceaeEubacteriaceae
GracekellibacteraceaePeptococcaceae
Peptostreptococcaceae
Peptostreptokleptococcaceae
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Lachnospiraceae and the Gastrointestinal Festival
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Lachnospiraceae respond to changing conditions in the gut and rumen
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Dorea(the explorea)
x2
Roseburiax2
Lachnospira
Lachnospiraceae astherapeutics?
Blautia
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Butyricacid
Ben Mills, https://commons.wikimedia.org/
Produced by many (…all?) Lachnospiraceae
- Important energy source. Thanks, microbiome!- Potential regulator of mucosal gene expression- Protective against some diseases (e.g. colitis)- Inhibitor of cancer cell proliferation?- Suppressor of C. difficile
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Taxonomy, phylogeny(16S and so on)
Function (genomes,metagenomes)
Ecology (distribution)
http://bighugelabs.com/badge.phpImage: http://ijsb.sgmjournals.org/content/53/1/201/F3.expansion
An identity for Lachnospiraceae?
Does everyone play the same ecological role (e.g., butyrate production?)
What sort of habitat differentiation exists in the group?
What is their relationship with other groups in the gut and elsewhere?
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Searching for Lachnospiraceae
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EMP samples collected from the QIIME database
GenGIS (http://kiwi.cs.dal.ca/GenGIS)
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Abundance in marker-gene samples
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Taxonomy, Phylogeny, Identity
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Co
nca
ten
ated
gen
es
SSU
Oral Human gut SedimentRumen
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Why the disagreement?
• Is 16S wrong?• Low support values at some nodes
• Is concatenation wrong?• Most individual gene trees reject the concatenated AND
16S phylogenies
• A mess due to lateral gene transfer?
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In search of ecological identity
• Is it butyrate production? Probably NO
Catonella morbi ATCC 51271Cellulosilyticum lentocellum DSM 5427Dorea formicigenerans ATCC 27755Dorea longicatena DSM 13814Lachnospiraceae bacterium 1_1_57FAALachnospiraceae bacterium 2_1_46FAALachnospiraceae bacterium 2_1_58FAALachnospiraceae bacterium 3_1_46FAALachnospiraceae bacterium 4_1_37FAALachnospiraceae bacterium 5_1_57FAALachnospiraceae bacterium 6_1_63FAALachnospiraceae bacterium 8_1_57FAALachnospiraceae bacterium 9_1_43BFAAMarvinbryantia formatexigens DSM 14469Oribacterium sinus F0268Oribacterium sp. oral taxon 078 str. F0262Oribacterium sp. oral taxon 108 str. F0425
Coprococcus eutactus ATCC 27759Butyrivibrio crossotus DSM 2876Butyrivibrio proteoclasticus B316Coprococcus comes ATCC 27758Lachnospiraceae bacterium 1_4_56FAALachnospiraceae bacterium 3_1_57FAA_CT1Shuttleworthia satelles DSM 14600Anaerostipes caccae DSM 14662Anaerostipes sp. 3_2_56FAALachnospiraceae bacterium 5_1_63FAALachnospiraceae oral taxon 107 str. F0167Roseburia intestinalis L1-82Roseburia inulinivorans DSM 16841
Showing 1 or 2 of the 3 known pathways
Showing 0 of the 3 known pathways
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Butyric acid production:three different ways, and a phylogenetic mess
Roseburia-type butyryl-CoA:acetate CoA-transferase
butyryl-CoA:acetate CoA-transferase
Butyrate kinase
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Gut-associated versus everyone else:
2 x sigma factor, 6 x sporulation protein, cell wall hydrolase (22/1)
3 x sporulation protein (22/0)
Others:
- penicillin-binding protein
- Antimicrobial extrusion protein
- Signal transduction / two-component regulators
- …
In search of ecological identity II
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Spo gene trees are largely consistent with one anotherSpo sigma factors present in all genomes– suggestive of LOSS in oral + rumen genomes
SpoIVA –sine qua non
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The metagenome picture
Lachnospiraceae-associated sporulationgenes in human gut vs. rumen metagenomes
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Mostly mammals: a Lachnospiraceae Love Story
• Drop acid• Butyrate production is readily gained and lost (as you
might expect)
• Lose your coat• The capacity for spore production has been lost several
times
• Leave in someone else’s genes• LGT has clearly impacted the group in a big way (to be
continued…)
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What next?
• Environmental distribution of different Lachnogroups
• Different abundances in healthy vs. diseased?
• Pathway-level analysis of butyrate vs. non-butyrate-producing strains
• Non-butyrate are enriched for a couple of “pathogenesis” genes, but nothing compelling yet
• Interesting split in the gut-associated strains
• Detailed profiling of LGT in the group
• New data that we cannot generate ourselves
• Transcriptomics!!
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Fin