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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»

Сравнительная геномика и метаболическая реконструкция бактериальных патогенов

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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

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    XII

  • : :

  • : (, -, ) : - - ( ) () : : , ,

  • : : - - ( ) : : : , ( , ) , , ( , ) ,

  • 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) ( )