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Сравнительная геномика и метаболическая реконструкция бактериальных патогенов. Михаил Гельфанд Институт проблем передачи информации РАН, Учебно-научный центр «Биоинформатика» XII Российский национальный конгресс «Человек и лекарство». Метаболическая реконструкция. - PowerPoint PPT Presentation
Citation preview
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XII
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: : - - ( ) : : : , ( , ) , , ( , ) ,
acpPfabDaccAaccDaccBaccCfabHfabFfabGfabZfabIGene fabI of Enoyl-ACP reductase (EC 1.3.1.9) is missing in the genome 12B, and a number of StreptococcifabI (Enoyl-ACP reductase, EC 1.3.1.9), . : ,
: -
FabR (Tr?, HTH)HTHfabKfabHacpPfabGfabFaccAaccDaccCaccBfabZfabDFad (42.1.17)1234
CONSENSUS
acTTTGAtwaTCAAAgt
E. faecalis
HTH-1
AgTTTGggTATCAAAGT
E. faecalis
HTH-2
AgTTTGAacATCAAAtg
E. faecalis
HTH-3
GtTTTGATAATCAAAGT
E. faecium
HTH-1
ACTTTGATAATCAAAaT
E. faecium
HTH-2
AgTTTGAacATCAAAag
E. faecium
HTH-3
gaTTTGATAATCAAAcT
S. pyogenes
4.2.1.17
GaTTTGATTATCAAAtg 1
S. pyogenes
HTH-1
AaTTTGATTgTCAAAGT 2
S. pyogenes
fabK-1
CtTTTGATAtTCAAAtT 3
S. pyogenes
fabK-2
AgTTTGATTATCAAAtT 4
S. pneumoniae
4.2.1.17
ACTTTGAcAgTgAAAta
S. pneumoniae
HTH-1
gtTTTGATTgTaAAAGT
S. pneumoniae
fabK-1
AgTTTGAcTgTCAAAtT
S. mutans
4.2.1.17-1
ACTTTGATTtTCAAAcT
S. mutans
4.2.1.17-2
AaTTTGATTATCttAaT
S. mutans
HTH-1
ACTTTGATAgTCAAAGT
S. mutans
fabK-1
AgTTTGAcAtTCAAAtc
S. mutans
fabK-2
AgTTTGAcTgTCAAAtT
( / )thiN (confirmed)(Gram-positive bacteria)(Gram-negative bacteria)Transport of HMPTransport of HETPurine pathway
, - +
1
S. pneumoniaeS. pyogenesS. equiS. uberisS. agalactiaeS. mutansS. thermophilusS. suisL. lactisL. caseiL. gasseriL. delbrueckiiP. pentosaceusL. brevisL. mesenteroidesOenococcus oeni
arabinose
arbutin
cellobiose
dextranFragmentary biochemical data
esculinExperimentally verified genes
fructoseOnly genomic prediction
fucoseBiochemical data and genomic prediction
galactose
glucose
inulin
lactose
maltose
mannitol
mannose
melibiose
N-AcGlu
raffinose
ribose
salicin
sorbitol
sorbose
sucrose
tagatose
trehalose
xylose
2
S. pneumoniaeS. pyogenesS. equiS. uberisS. agalactiaeS. mutansS. thermophilusS. suisL. lactisL. caseiL. gasseriL. delbrueckiiP. pentosaceusL. brevisL. mesenteroidesOenococcus oeni
amygdalin+++++/-
arabinose++/---+/-++
arbutin+++++++/-
cellobiose-+++-++++/-
dextran+++++
esculin+?+-++++/-+
fructose+*+++++++++++
fucose++----
galactose+*++++++/-+++++++
glucose++++++++++++++++
inulin+--+/--+++++-
lactose+++/-++/-++++++++++/-
maltose+++?++++-++++-++
mannitol---+-++-+/-++-+?+/-
mannose+?+++-++++
melibiose-+/-++-/++/-
N-AcGlu++++++
pullulan++?+
raffinose++--+/--+++-/++/-
ribose-*-+/-+/-+-+++
salicin-++++/-+++++++/-
sorbitol--+/-+-++--++
sorbose-----++-
sucrose+*++++++++++-+
tagatose--?+-
trehalose+*+-++/-++?-+/-++-+
xylose+---++/-++/-++++/-
3
S. pneumoniaeS. pyogenesS. equiS. uberisS. agalactiaeS. mutansS. thermophilusS. suisL. lactisL. caseiL. gasseriL. delbrueckiiP. pentosaceusL. brevisL. mesenteroidesOenococcus oeni
unknown
arabinose
arbutin
cellobiose
dextranFragmentary biochemical data
esculinExperimentally verified genes
fructoseOnly genomic prediction
fucoseBiochemical data and genomic prediction
galactose
glucose
inulin
lactose
maltose
mannitol
mannose
melibiose
N-AcGlu
raffinose
ribose
salicin
sorbitol
sorbose
sucrose
tagatose
trehalose
xylose
1
S. pneumoniaeS. pyogenesS. equiS. uberisS. agalactiaeS. mutansS. thermophilusS. suisL. lactisL. caseiL. gasseriL. delbrueckiiP. pentosaceusL. brevisL. mesenteroidesOenococcus oeni
arabinose
arbutin
cellobiose
dextranFragmentary biochemical data
esculinExperimentally verified genes
fructoseOnly genomic prediction
fucoseBiochemical data and genomic prediction
galactose
glucose
inulin
lactose
maltose
mannitol
mannose
melibiose
N-AcGlu
raffinose
ribose
salicin
sorbitol
sorbose
sucrose
tagatose
trehalose
xylose
2
S. pneumoniaeS. pyogenesS. equiS. uberisS. agalactiaeS. mutansS. thermophilusS. suisL. lactisL. caseiL. gasseriL. delbrueckiiP. pentosaceusL. brevisL. mesenteroidesOenococcus oeni
amygdalin+++++/-
arabinose++/---+/-++
arbutin+++++++/-
cellobiose-+++-++++/-
dextran+++++
esculin+?+-++++/-+
fructose+*+++++++++++
fucose++----
galactose+*++++++/-+++++++
glucose++++++++++++++++
inulin+--+/--+++++-
lactose+++/-++/-++++++++++/-
maltose+++?++++-++++-++
mannitol---+-++-+/-++-+?+/-
mannose+?+++-++++
melibiose-+/-++-/++/-
N-AcGlu++++++
pullulan++?+
raffinose++--+/--+++-/++/-
ribose-*-+/-+/-+-+++
salicin-++++/-+++++++/-
sorbitol--+/-+-++--++
sorbose-----++-
sucrose+*++++++++++-+
tagatose--?+-
trehalose+*+-++/-++?-+/-++-+
xylose+---++/-++/-++++/-
3
1
S. pneumoniaeS. pyogenesS. equiS. uberisS. agalactiaeS. mutansS. thermophilusS. suisL. lactisL. caseiL. gasseriL. delbrueckiiP. pentosaceusL. brevisL. mesenteroidesOenococcus oeni
arabinose
arbutin
cellobiose
dextranFragmentary biochemical data
esculinExperimentally verified genes
fructoseOnly genomic prediction
fucoseBiochemical data and genomic prediction
galactose
glucose
inulin
lactose
maltose
mannitol
mannose
melibiose
N-AcGlu
raffinose
ribose
salicin
sorbitol
sorbose
sucrose
tagatose
trehalose
xylose
2
S. pneumoniaeS. pyogenesS. equiS. uberisS. agalactiaeS. mutansS. thermophilusS. suisL. lactisL. caseiL. gasseriL. delbrueckiiP. pentosaceusL. brevisL. mesenteroidesOenococcus oeni
amygdalin+++++/-
arabinose++/---+/-++
arbutin+++++++/-
cellobiose-+++-++++/-
dextran+++++
esculin+?+-++++/-+
fructose+*+++++++++++
fucose++----
galactose+*++++++/-+++++++
glucose++++++++++++++++
inulin+--+/--+++++-
lactose+++/-++/-++++++++++/-
maltose+++?++++-++++-++
mannitol---+-++-+/-++-+?+/-
mannose+?+++-++++
melibiose-+/-++-/++/-
N-AcGlu++++++
pullulan++?+
raffinose++--+/--+++-/++/-
ribose-*-+/-+/-+-+++
salicin-++++/-+++++++/-
sorbitol--+/-+-++--++
sorbose-----++-
sucrose+*++++++++++-+
tagatose--?+-
trehalose+*+-++/-++?-+/-++-+
xylose+---++/-++/-++++/-
3
1
S. pneumoniaeS. pyogenesS. equiS. uberisS. agalactiaeS. mutansS. thermophilusS. suisL. lactisL. caseiL. gasseriL. delbrueckiiP. pentosaceusL. brevisL. mesenteroidesOenococcus oeni
arabinose
arbutin
cellobiose
dextranFragmentary biochemical data
esculinExperimentally verified genes
fructoseOnly genomic prediction
fucoseBiochemical data and genomic prediction
galactose
glucose
inulin
lactose
maltose
mannitol
mannose
melibiose
N-AcGlu
raffinose
ribose
salicin
sorbitol
sorbose
sucrose
tagatose
trehalose
xylose
2
S. pneumoniaeS. pyogenesS. equiS. uberisS. agalactiaeS. mutansS. thermophilusS. suisL. lactisL. caseiL. gasseriL. delbrueckiiP. pentosaceusL. brevisL. mesenteroidesOenococcus oeni
amygdalin+++++/-
arabinose++/---+/-++
arbutin+++++++/-
cellobiose-+++-++++/-
dextran+++++
esculin+?+-++++/-+
fructose+*+++++++++++
fucose++----
galactose+*++++++/-+++++++
glucose++++++++++++++++
inulin+--+/--+++++-
lactose+++/-++/-++++++++++/-
maltose+++?++++-++++-++
mannitol---+-++-+/-++-+?+/-
mannose+?+++-++++
melibiose-+/-++-/++/-
N-AcGlu++++++
pullulan++?+
raffinose++--+/--+++-/++/-
ribose-*-+/-+/-+-+++
salicin-++++/-+++++++/-
sorbitol--+/-+-++--++
sorbose-----++-
sucrose+*++++++++++-+
tagatose--?+-
trehalose+*+-++/-++?-+/-++-+
xylose+---++/-++/-++++/-
3
1
S. pneumoniaeS. pyogenesS. equiS. uberisS. agalactiaeS. mutansS. thermophilusS. suisL. lactisL. caseiL. gasseriL. delbrueckiiP. pentosaceusL. brevisL. mesenteroidesOenococcus oeni
arabinose
arbutin
cellobiose
dextranFragmentary biochemical data
esculinExperimentally verified genes
fructoseOnly genomic prediction
fucoseBiochemical data and genomic prediction
galactose
glucose
inulin
lactose
maltose
mannitol
mannose
melibiose
N-AcGlu
raffinose
ribose
salicin
sorbitol
sorbose
sucrose
tagatose
trehalose
xylose
2
S. pneumoniaeS. pyogenesS. equiS. uberisS. agalactiaeS. mutansS. thermophilusS. suisL. lactisL. caseiL. gasseriL. delbrueckiiP. pentosaceusL. brevisL. mesenteroidesOenococcus oeni
amygdalin+++++/-
arabinose++/---+/-++
arbutin+++++++/-
cellobiose-+++-++++/-
dextran+++++
esculin+?+-++++/-+
fructose+*+++++++++++
fucose++----
galactose+*++++++/-+++++++
glucose++++++++++++++++
inulin+--+/--+++++-
lactose+++/-++/-++++++++++/-
maltose+++?++++-++++-++
mannitol---+-++-+/-++-+?+/-
mannose+?+++-++++
melibiose-+/-++-/++/-
N-AcGlu++++++
pullulan++?+
raffinose++--+/--+++-/++/-
ribose-*-+/-+/-+-+++
salicin-++++/-+++++++/-
sorbitol--+/-+-++--++
sorbose-----++-
sucrose+*++++++++++-+
tagatose--?+-
trehalose+*+-++/-++?-+/-++-+
xylose+---++/-++/-++++/-
3
S. pneumoniaeS. pyogenesS. equiS. agalactiaeS. suis
1
S. pneumoniaeS. pyogenesS. equiS. uberisS. agalactiaeS. mutansS. thermophilusS. suisL. lactisL. caseiL. gasseriL. delbrueckiiP. pentosaceusL. brevisL. mesenteroidesOenococcus oeni
arabinose
arbutin
cellobiose
dextranFragmentary biochemical data
esculinExperimentally verified genes
fructoseOnly genomic prediction
fucoseBiochemical data and genomic prediction
galactose
glucose
inulin
lactose
maltose
mannitol
mannose
melibiose
N-AcGlu
raffinose
ribose
salicin
sorbitol
sorbose
sucrose
tagatose
trehalose
xylose
2
S. pneumoniaeS. pyogenesS. equiS. uberisS. agalactiaeS. mutansS. thermophilusS. suisL. lactisL. caseiL. gasseriL. delbrueckiiP. pentosaceusL. brevisL. mesenteroidesOenococcus oeni
amygdalin+++++/-
arabinose++/---+/-++
arbutin+++++++/-
cellobiose-+++-++++/-
dextran+++++
esculin+?+-++++/-+
fructose+*+++++++++++
fucose++----
galactose+*++++++/-+++++++
glucose++++++++++++++++
inulin+--+/--+++++-
lactose+++/-++/-++++++++++/-
maltose+++?++++-++++-++
mannitol---+-++-+/-++-+?+/-
mannose+?+++-++++
melibiose-+/-++-/++/-
N-AcGlu++++++
pullulan++?+
raffinose++--+/--+++-/++/-
ribose-*-+/-+/-+-+++
salicin-++++/-+++++++/-
sorbitol--+/-+-++--++
sorbose-----++-
sucrose+*++++++++++-+
tagatose--?+-
trehalose+*+-++/-++?-+/-++-+
xylose+---++/-++/-++++/-
3
S. pneumoniaeS. pyogenesS. equiS. uberisS. agalactiaeS. mutansS. thermophilusS. suisL. lactisL. caseiL. gasseriL. delbrueckiiP. pentosaceusL. brevisL. mesenteroidesOenococcus oeni
unknown
arabinose
arbutin
cellobiose
dextranFragmentary biochemical data
esculinExperimentally verified genes
fructoseOnly genomic prediction
fucoseBiochemical data and genomic prediction
galactose
glucose
inulin
lactose
maltose
mannitol
mannose
melibiose
N-AcGlu
raffinose
ribose
salicin
sorbitol
sorbose
sucrose
tagatose
trehalose
xylose
S. pyogenes, S. agalactiaeS. equiS. pneumoniae TIGR4S. suisS. pneumoniae R6
3-(4-deoxy-beta-D-gluc-4-enuronosyl)-N-acetyl-D-glucosamine PTS transporterhydrolaseisomeraseoxidoreductasedehydrogenasekinasealdolasepyruvate + D-glyceraldehyde 3-phosphate
- 2S. pyogenes, S. agalactiaeS. equiS. pneumoniae TIGR4S. suisS. pneumoniae R6
- -
: ,
:
: -, , ..
:
nZUR FUR family???AdcR ? MarR familypZUR FUR family
nZUR-nZUR-AdcRpZURTTAACYRGTTAAGATATGTTATAACATATCGAAATGTTATANTATAACATTTCGTAATGTAATAACATTACTAAATCGTAATNATTACGATTTA
AdcABC YciC AdcABC YciC
zinT: zinT is isolated fusion: adcA-zinTE. coli, S. typhi, K. pneumoniaeGamma-proteobacteriaAlpha-proteobacteriaB. subtilis, S. aureusS. pneumoniae, S. mutans, S. pyogenes, L. lactis, E. faecalisBacillus groupStreptococcus groupzinT is regulated by zinc repressors (nZUR-, nZUR-, pZUR)adcA-zinT is regulated by zinc repressors (pZUR, AdcR) (ex. L.l.)A. tumefaciens, R. sphaeroides
ZinT: E. coli, S. typhi, K. pneumoniae, A. tumefaciens, R. sphaeroides, B. subtilisL. lactisY. pestis, V. cholerae, B. haloduransTMZnAdcAS. aureus, E. faecalis, S. pneumoniae, S. mutans, S. pyogenesZinT
ZinT: zinT adcAzinT ZinT ( )ZinT - ZinT: ZinT - ABC-
, PHT- (pneumococcal histidine triad) S. pneumoniaeS. equiS. agalactiaephtEphtBphtAlmbphtDS. pyogenesphtYlmbphtD
PH-PHT- HxxHxHPHT- S. pneumoniae - (65-95% )Sec- N- PHT- S. pneumoniae
PH-: PHT- PHT- PHT- - :PHT-
- :
EEEHEEHDHGEHEHSH
HSHEEHGHEEDDHDHSHEEHGHEEDDHHHHHDED
DEHGEGHEEEHGHEH
(--) :
HGDHYHY7 out of 21HGDHYHF2 out of 21HGNHYHF2 out of 21HYDHYHN2 out of 21HMTHSHW2 out of 21
( )
PH- () phtD lmb Lmb: , PhtY S. pyogenes: phtY AdcRPhtY :4 HIS TRIADS
PH-: -2PHT- PHT- PHT- - phtD PhtY , PHT- , ,
nZURpZURAdcR
L36L33L31S14E. coli, S.typhi +K. pneumoniae Y. pestis,V. cholerae +B subtilis + + +S. aureus +Listeria spp. +E. faecalis + S. pne., S. mutans S. pyo., L. lactis +
(Makarova-Ponomarev-Koonin, 2001)nZURpZURAdcR
L36L33L31S14E. coli, S.typhi()() +K. pneumoniae()() Y. pestis,V. cholerae() () +B subtilis() () + () +() +S. aureus()() () +Listeria spp.()() () +E. faecalis()() () + S. pne., S. mutans()() ()S. pyo., L. lactis()() () +
:Makarova-Ponomarev-Koonin, 2001:L36, L33, L31, S14 , L36, L33, L31, S14 , ( ) ( ) L36, L33, L31, S14 , , , () ,
: ,
ribosomesZn-dependent enzymesRSufficient ZnZn starvationRrepressor
: ,
(Proc Natl Acad Sci U S A. 2003 Aug 19;100(17):9912-7.) (Mol Microbiol. 2004 Apr;52(1):273-83.)
() () () ( UCLA, USA) .. () () ( LORIA, France)Howard Hughes Medical Institute Ludwig Institute of Cancer Research ( ) (Burnham Institute, San-Diego, USA) ( )