Helicobacter pylori rpoB mutation conferring resistance to rifampicin

Accession ARO:3007051
CARD Short NameHpyl_rpoB_RIF
DefinitionRifampicin inhibits transcription by binding the beta subunit of RNA polymerase. Helicobacter pylori mutations associated with rifampicin resistance typically occur in the rifampicin resistance determining region of rpoB between codons 525 and 586.
AMR Gene Familyrifamycin-resistant beta-subunit of RNA polymerase (rpoB)
Drug Classrifamycin antibiotic, fluoroquinolone antibiotic
Resistance Mechanismantibiotic target alteration, antibiotic target replacement
Resistomes with Sequence VariantsHelicobacter pylorig+wgs
Classification12 ontology terms | Show
Parent Term(s)3 ontology terms | Show
+ rifamycin-resistant beta-subunit of RNA polymerase (rpoB) [AMR Gene Family]
+ confers_resistance_to_antibiotic rifampin [Antibiotic]
+ confers_resistance_to_antibiotic levofloxacin [Antibiotic]
Publications

Heep M, et al. 1999. Antimicrob Agents Chemother 43(6):1497-9 Rifampin and rifabutin resistance mechanism in Helicobacter pylori. (PMID 10348780)

Glocker E, et al. 2007. J Antimicrob Chemother 59(5):874-9 Characterization of rifampicin-resistant clinical Helicobacter pylori isolates from Germany. (PMID 17350989)

Miftahussurur M, et al. 2019. Antimicrob Resist Infect Control 8:40 Effective therapeutic regimens in two South Asian countries with high resistance to major Helicobacter pylori antibiotics. (PMID 30815255)

Miftahussurur M, et al. 2019. Infect Drug Resist 12:345-358 Alternative eradication regimens for Helicobacter pylori infection in Indonesian regions with high metronidazole and levofloxacin resistance. (PMID 30774400)

Heep M, et al. 2000. Antimicrob Agents Chemother 44(6):1713-5 Mutations at four distinct regions of the rpoB gene can reduce the susceptibility of Helicobacter pylori to rifamycins. (PMID 10817737)

Resistomes

Prevalence of Helicobacter pylori rpoB mutation conferring resistance to rifampicin among the sequenced genomes, plasmids, and whole-genome shotgun assemblies available at NCBI or IslandViewer for 413 important pathogens (see methodological details and complete list of analyzed pathogens). Values reflect percentage of genomes, plasmids, genome islands, or whole-genome shotgun assemblies that have at least one hit to the AMR detection model. Default view includes percentages calculated based on Perfect plus Strict RGI hits. Select the checkbox to view percentages based on only Perfect matches to AMR reference sequences curated in CARD (note: this excludes resistance via mutation as references in protein variant models are often wild-type, sensitive sequences).

Prevalence: protein variant model (view sequences)

SpeciesNCBI ChromosomeNCBI PlasmidNCBI WGSNCBI GI
Helicobacter pylori36.67%0%48.76%0%
Show Perfect Only


Detection Models

Model Type: protein variant model

Model Definition: Protein Variant Models (PVM) perform a similar search as Protein Homolog Models (PHM), i.e. detect protein sequences based on their similarity to a curated reference sequence, but secondarily screen query sequences for curated sets of mutations to differentiate them from antibiotic susceptible wild-type alleles. PVMs are designed to detect AMR acquired via mutation of house-keeping genes or antibiotic targets, e.g. a mutated gyrase resistant to aminocoumarin antibiotics. PVMs include a protein reference sequence (often from antibiotic susceptible wild-type alleles), a curated bit-score cut-off, and mapped resistance variants. Mapped resistance variants may include any or all of single point mutations, insertions, or deletions curated from the scientific literature. A Strict RGI match has a BLASTP bit-score above the curated BLASTP cutoff value and contains at least one curated mutation from amongst the mapped resistance variants, while a Loose RGI match has a bit-score less than the curated BLASTP bit-score cut-off but still contains at least one curated mutation from amongst the mapped resistance variants.

Bit-score Cut-off (blastP): 3000

Legend:

  • discovered in clinical, agricultural, or environmental isolates

  • discovered via laboratory selection experiments

  • ReSeqTB https://platform.reseqtb.org

Published Variants:

PMID: 10348780L525P Q527R Q527K D530V S545L I586L I586N
PMID: 17350989L525I D530N D530E D530G D530F D530I D530Y D530L H540N H540Y
PMID: 30815255T2537A F2538L V2592L I2619V
PMID: 30774400I837V K2068R Q2079K A2414V A2414T
PMID: 10817737V148I,V149F V149W V149D V149E V149Q V149K V149F R701H

>gb|AAD08242.1|-|Helicobacter pylori rpoB mutation conferring resistance to rifampicin [Helicobacter pylori 26695]
MSKKIPLKNRLRADFTKTPTDLEVPNLLLLQRDSYDSFLYSKEGKESGIEKVFKSIFPIQ
DEHNRITLEYAGCEFGKSKYTVREAMERGITYSIPLKIKVRLILWEKDTKSGEKNGIKDI
KEQSIFIREIPLMTERTSFIINGVERVVVNQLHRSPGVIFKEEESSTSLNKLIYTGQIIP
DRGSWLYFEYDSKDVLYARINKRRKVPVTILFRAMDYQKQDIIKMFYPLVKVRYENDKYL
IPFASLDANQRMEFDLKDPQGKVILLAGKKLTSRKIKELKENHLEWVEYPMDILLNRHLA
EPVMVGKEVLLDMLTQLDKNKLEKIHDLGVQEFVIINDLALGHDASIIQSFSADSESLKL
LKQTEKIDDENALAAIRIHKVMKPGDPVTTEVAKQFVKKLFFDPERYDLTMVGRMKMNHK
LGLHVPDYITTLTHEDIITTVKYLMKIKNNQGKIDDRDHLGNRRIRAVGELLANELHSGL
VKMQKTIKDKLTTMSGAFDSLMPHDLVNSKMITSTIMEFFMGGQLSQFMDQTNPLSEVTH
KRRLSALGEGGLVKDRVGFEARDVHPTHYGRICPIETPEGQNIGLINTLSTFTRVNDLGF
IEAPYKKVVDGKVVGETIYLTAIQEDSHIIAPASTPIDEEGNILGDLIETRVEGEIVLNE
KSKVTLMDLSSSMLVGVAASLIPFLEHDDANRALMGTNMQRQAVPLLRSDAPIVGTGIEK
IIARDSWGAIKANRAGVVEKIDSKNIYILGESKEEAYIDAYSLQKNLRTNQNTSFNQVPI
VKVGDKVGAGQIIADGPSMDRGELALGKNVRVAFMPWNGYNFEDAIVVSECITKDDIFTS
THIYEKEVDARELKHGVEEFTADIPDVKEEALAHLDESGIVKVGTYVSAGMILVGKTSPK
GEIKSTPEERLLRAIFGDKAGHVVNKSLYCPPSLEGTVIDVKVFTKKGYEKDARVLSAYE
EEKAKLDMEHFDRLTMLNREELLRVSSLLSQAILEEPFSHNGKDYKEGDQIPKEEIASIN
RFTLASLVKKYSKEVQNHYEITKNNFLEQKKVLGEEHEEKLSILEKDDILPNGVIKKVKL
YIATKRKLKVGDKMAGRHGNKGIVSNIVPVADMPYTADGEPVDIVLNPLGVPSRMNIGQI
LEMHLGLVGKEFGKQIARMLEDKTKDFAKELRAKMLEIANAINEKDPLTIHALENCSDEE
LLEYAKDWSKGVKMAIPVFEGISQEKFYKLFELAKIAMDGKMDLYDGRTGEKMRERVNVG
YMYMIKLHHLVDEKVHARSTGPYSLVTHQPVGGKALFGGQRFGEMEVWALEAYGAAHTLK
EMLTIKSDDIRGRENAYRAIAKGEQVGESEIPETFYVLTKELQSLALDINIFGDDVDEDG
APKPIVIKEDDRPKDFSSFQLTLASPEKIHSWSYGEVKKPETINYRTLKPERDGLFCMKI
FGPTKDYECLCGKYKKPRFKDIGTCEKCGVAITHSKVRRFRMGHIELATPVAHIWYVNSL
PSRIGTLLGVKMKDLERVLYYEAYIVKEPGEAAYDNEGTKLVMKYDILNEEQYQNISRRY
EDRGFVAQMGGEAIKDLLEEIDLITLLQSLKEEVKDTNSDAKKKKLIKRLKVVESFLNSG
NRPEWMMLTVLPVLPPDLRPLVALDGGKFAVSDVNELYRRVINRNQRLKRLMELGAPEII
VRNEKRMLQEAVDVLFDNGRSTNAVKGANKRPLKSLSEIIKGKQGRFRQNLLGKRVDFSG
RSVIVVGPNLKMDECGLPKNMALELFKPHLLSKLEERGYATTLKQAKRMIEQKSNEVWEC
LQEITEGYPVLLNRAPTLHKQSIQAFHPKLIDGKAIQLHPLVCSAFNADFDGDQMAVHVP
LSQEAIAECKVLMLSSMNILLPASGKAVAIPSQDMVLGLYYLSLEKSGVKGEHKLFSSVN
EIITAIDTKELDIHAKIRVLDQGNIIATSAGRMIIKSILPDFIPTDLWNRPMKKKDIGVL
VDYVHKVGGIGITATFLDNLKTLGFRYATKAGISISMEDIITPKDKQKMVEKAKVEVKKI
QQQYDQGLLTDQERYNKIIDTWTEVNDKMSKEMMTAIAQDKEGFNSIYMMADSGARGSAA
QIRQLSAMRGLMTKPDGSIIETPIISNFKEGLNVLEYFNSTHGARKGLADTALKTANAGY
LTRKLIDVSQNVKVVSDDCGTHEGIEITDIAVGSELIEPLEERIFGRVLLEDVIDPITNE
ILLYADTLIDEEGAKKVVEAGIKSITIRTPVTCKAPKGVCAKCYGLNLGEGKMSYPGEAV
GVVAAQSIGEPGTQLTLRTFHVGGTASRSQDEREIVASKEGFVRFYNLRTYTNKEGKNII
ANRRNASILVVEPKIKAPFDGELRIETVYEEVVVSVKNGDQEAKFVLRRSDIVKPSELAG
VGGKIEGKVYLPYASGHKVHKGGSIADIIQEGWNVPNRIPYASELLVKDNDPIAQDVYAK
EKGVIKYYVLEANHLERTHGIKKGDMVSEKGLFAVIADDNGREAARHYIARGSEILIDDN
SEVSTNSVISKPTTNTFKTIATWDPYNTPIIADFKGKVGFVDVIAGVTVAEKEDENTGIT
SLVVNDYIPSGYKPSLFLEGANGEEMRYFLEPKTSIAISDGSSVEQAEVLAKIPKATVKS
RDITGGLPRVSELFEARKPKPKDVAILSEVDGIVSFGKPIRNKEHIIVTSKDGRSMDYFV
DKGKQILVHADEFVHAGEAMTDGVISSHDILRISGEKELYKYIVSEVQQVYRRQGVSIAD
KHIEIIVSQMLRQVRILDSGDSKFIEGDLVSKKLFKEENARVIALKGEPAIAEPVLLGIT
RAAIGSDSIISAASFQETTKVLTEASIAMKKDFLEDLKENVVLGRMIPVGTGMYKNKKIV
LRALEDNSKF



>gb|AE000511.1|-|1268377-1277049|Helicobacter pylori rpoB mutation conferring resistance to rifampicin [Helicobacter pylori 26695]
ATGTCAAAAAAAATTCCCCTAAAAAACCGCTTGAGAGCTGATTTTACAAAAACCCCAACAGATTTAGAAGTCCCTAATTTATTATTATTA
CAACGAGACAGCTATGATTCTTTCTTGTATTCTAAAGAGGGTAAAGAGAGCGGGATTGAAAAGGTTTTTAAATCCATTTTCCCTATCCAA
GATGAGCATAACCGCATCACTTTAGAATACGCGGGTTGCGAATTTGGCAAGTCTAAATACACCGTTAGAGAAGCGATGGAGAGGGGCATT
ACCTACTCTATCCCTCTCAAAATTAAGGTGCGCTTGATCTTGTGGGAAAAAGATACCAAGAGTGGCGAAAAGAACGGCATTAAGGATATT
AAAGAACAAAGCATTTTCATTCGTGAGATCCCTTTGATGACAGAACGCACTTCATTTATTATTAATGGGGTGGAGCGCGTGGTGGTCAAT
CAACTCCACAGAAGCCCCGGTGTGATTTTCAAAGAAGAAGAGTCTAGCACTTCTTTAAACAAGCTCATTTACACAGGGCAAATCATTCCT
GATAGGGGTTCGTGGTTGTATTTTGAATACGATTCTAAAGATGTTTTATACGCTCGTATCAATAAACGCCGTAAAGTGCCTGTTACCATT
TTATTCAGGGCGATGGATTATCAAAAACAAGACATCATCAAAATGTTCTACCCGCTTGTTAAAGTGCGTTATGAAAACGATAAATATTTG
ATCCCGTTTGCTTCATTAGACGCCAATCAAAGAATGGAATTTGACTTGAAAGATCCTCAAGGCAAGGTTATTCTTTTAGCGGGTAAAAAG
CTCACTTCAAGAAAGATTAAAGAGCTTAAAGAAAACCATTTAGAATGGGTGGAATACCCTATGGATATTTTACTCAATCGCCATTTAGCT
GAGCCTGTTATGGTAGGGAAAGAAGTCTTATTGGACATGCTCACTCAGCTAGATAAAAACAAATTAGAAAAAATCCACGATTTAGGCGTG
CAAGAATTTGTGATCATCAACGATCTGGCGTTAGGGCATGACGCTTCCATTATCCAATCTTTTTCAGCCGATTCTGAGTCTTTGAAATTA
CTCAAGCAAACCGAAAAAATTGATGATGAAAACGCTCTAGCGGCGATTCGTATCCATAAGGTTATGAAACCAGGCGATCCCGTTACGACT
GAAGTGGCTAAGCAGTTTGTCAAAAAACTTTTCTTTGATCCAGAACGCTATGATTTGACCATGGTGGGCCGCATGAAAATGAATCACAAG
TTAGGCTTGCATGTGCCTGATTACATTACGACTTTAACGCATGAAGATATTATCACCACCGTTAAATACCTCATGAAGATCAAAAACAAT
CAAGGCAAGATTGATGACAGGGACCACTTGGGCAATCGTAGGATTAGGGCGGTAGGGGAATTGTTGGCCAATGAATTGCATTCAGGTTTA
GTGAAAATGCAAAAGACCATTAAAGACAAGCTCACTACCATGAGCGGGGCTTTTGATTCGCTCATGCCCCATGACTTGGTCAATTCTAAA
ATGATCACAAGCACCATCATGGAATTTTTCATGGGCGGTCAGCTCTCGCAATTTATGGATCAAACGAATCCCTTGAGTGAGGTTACGCAC
AAGCGCCGCCTTTCAGCGCTCGGCGAAGGGGGGTTGGTGAAAGACAGAGTGGGGTTTGAAGCCAGGGATGTGCACCCCACGCATTATGGC
CGAATTTGTCCCATTGAGACCCCAGAAGGTCAAAATATCGGTCTGATCAACACCCTTTCCACTTTCACAAGAGTGAATGATTTAGGCTTT
ATTGAAGCCCCTTATAAAAAGGTTGTGGATGGCAAGGTCGTGGGTGAGACGATTTATTTGACCGCTATTCAAGAAGACAGCCACATCATC
GCTCCCGCAAGCACCCCCATTGATGAAGAGGGGAATATTTTGGGCGATTTGATTGAAACGCGCGTGGAAGGCGAGATCGTTTTAAACGAA
AAAAGCAAAGTAACCTTAATGGATTTAAGCTCTAGCATGCTAGTGGGGGTAGCCGCATCGCTCATTCCTTTCTTAGAGCATGATGACGCC
AACCGTGCCTTAATGGGGACTAACATGCAGCGCCAAGCGGTGCCCTTATTAAGAAGCGACGCTCCCATTGTAGGCACGGGGATTGAAAAA
ATTATTGCTAGGGATTCTTGGGGAGCGATCAAAGCCAATCGCGCAGGCGTTGTAGAAAAAATTGATTCTAAAAATATTTATATTTTAGGC
GAAAGCAAAGAAGAAGCCTATATTGATGCGTATTCTTTGCAAAAAAACTTGCGCACCAACCAAAACACCAGTTTCAATCAAGTCCCTATC
GTTAAAGTGGGCGATAAAGTGGGAGCCGGGCAAATCATCGCTGATGGCCCTAGCATGGATAGAGGCGAGTTGGCGTTAGGGAAAAATGTG
CGCGTGGCGTTCATGCCTTGGAATGGCTATAACTTTGAAGACGCGATCGTGGTGAGTGAGTGCATCACTAAAGATGATATTTTCACTTCC
ACCCACATTTATGAAAAAGAAGTGGATGCTAGGGAGCTTAAGCATGGTGTGGAAGAATTTACCGCTGATATTCCTGATGTGAAAGAAGAA
GCGCTCGCTCATCTTGATGAAAGCGGGATCGTTAAAGTCGGTACTTATGTGAGCGCTGGCATGATTTTGGTGGGCAAAACTTCTCCTAAA
GGCGAGATTAAAAGCACGCCTGAAGAGCGGCTTTTAAGGGCTATTTTTGGGGATAAAGCCGGGCATGTGGTCAATAAGAGTTTGTATTGC
CCTCCCAGTTTGGAAGGCACGGTGATTGATGTGAAAGTCTTCACTAAAAAAGGCTATGAGAAAGACGCGCGAGTTTTGAGCGCGTATGAA
GAAGAAAAAGCCAAGCTTGATATGGAGCATTTTGATCGCTTGACCATGCTCAATAGAGAAGAATTGTTGCGCGTTAGCTCGCTCCTTTCT
CAAGCGATTTTAGAAGAGCCTTTCAGCCATAACGGCAAGGATTATAAAGAAGGCGATCAAATCCCTAAAGAAGAAATCGCTTCAATCAAC
CGCTTCACTTTGGCTAGTTTGGTCAAAAAGTATTCTAAAGAAGTGCAAAACCACTATGAAATCACTAAAAACAATTTCTTAGAGCAAAAG
AAAGTTTTGGGCGAAGAGCATGAAGAAAAGCTTTCTATTTTAGAAAAAGATGATATTTTGCCTAATGGCGTGATCAAAAAAGTCAAGCTC
TATATCGCTACAAAACGAAAGCTTAAAGTGGGCGATAAAATGGCAGGAAGGCATGGGAATAAAGGGATTGTGTCTAATATCGTGCCGGTT
GCGGATATGCCTTATACCGCTGATGGCGAGCCTGTAGATATTGTTTTAAACCCTTTAGGCGTGCCAAGCCGCATGAATATCGGGCAGATT
TTAGAAATGCATTTAGGCTTAGTGGGGAAAGAATTTGGGAAGCAAATCGCTCGCATGCTAGAGGATAAAACCAAAGATTTTGCCAAAGAA
TTGCGTGCTAAAATGCTAGAAATCGCTAACGCTATTAATGAAAAAGACCCCTTGACAATCCATGCGCTTGAGAATTGTTCTGATGAAGAG
CTTTTGGAATACGCAAAAGATTGGAGCAAGGGCGTTAAGATGGCTATCCCTGTGTTTGAAGGCATCTCGCAAGAAAAATTTTATAAGCTA
TTTGAATTAGCTAAGATCGCTATGGATGGCAAAATGGATCTGTATGACGGACGCACAGGCGAGAAAATGAGGGAGCGCGTGAATGTGGGC
TACATGTATATGATCAAACTCCACCATTTAGTGGATGAAAAAGTCCATGCCAGAAGCACAGGCCCTTATAGCTTAGTAACGCACCAGCCC
GTGGGGGGTAAAGCGCTCTTTGGGGGTCAAAGGTTTGGGGAAATGGAAGTGTGGGCCTTGGAAGCTTATGGCGCAGCGCACACTCTAAAA
GAAATGCTCACCATTAAATCCGATGATATTAGAGGCAGAGAGAACGCTTATAGGGCTATCGCTAAAGGTGAGCAAGTGGGCGAGAGTGAA
ATCCCTGAGACTTTCTATGTTTTGACTAAAGAATTGCAATCGCTCGCTTTGGATATTAATATTTTTGGGGACGATGTGGATGAGGATGGA
GCACCTAAACCCATTGTCATTAAAGAAGATGACAGGCCTAAAGACTTTAGCTCTTTCCAGCTCACACTAGCTAGCCCTGAAAAAATCCAT
TCTTGGAGTTATGGGGAAGTTAAAAAGCCAGAAACGATCAATTATCGCACCCTAAAACCTGAACGAGACGGCTTGTTTTGCATGAAAATC
TTTGGCCCCACTAAAGATTATGAATGCTTGTGCGGCAAATACAAAAAGCCTCGCTTCAAAGACATTGGCACATGCGAAAAATGCGGCGTG
GCGATCACGCACTCCAAAGTCAGGCGTTTTAGAATGGGGCATATTGAATTGGCCACTCCTGTAGCGCATATCTGGTATGTTAATTCCTTG
CCTAGCCGTATCGGCACGCTTTTAGGCGTTAAGATGAAAGACTTAGAGCGCGTGTTGTATTATGAAGCTTATATCGTTAAAGAACCAGGC
GAAGCCGCTTATGACAATGAAGGCACTAAGCTTGTGATGAAATACGATATTTTGAATGAAGAGCAGTATCAAAATATCTCACGAAGATAC
GAAGACAGGGGCTTTGTAGCGCAAATGGGCGGTGAAGCGATCAAGGATTTGTTAGAAGAAATTGATTTGATCACCTTATTGCAGAGTTTG
AAAGAAGAAGTGAAAGACACCAATTCTGATGCGAAAAAGAAAAAACTCATTAAGCGTTTGAAAGTGGTAGAAAGCTTTTTAAATTCTGGT
AATAGGCCTGAATGGATGATGCTCACGGTTTTACCGGTATTGCCACCGGATTTAAGGCCTTTAGTCGCGCTAGATGGCGGGAAGTTTGCA
GTCAGCGATGTGAATGAATTGTATCGTCGTGTCATCAATCGTAACCAACGCTTGAAACGCTTAATGGAGCTTGGAGCGCCAGAAATCATT
GTGCGCAATGAAAAAAGGATGTTGCAAGAAGCCGTGGATGTGCTTTTTGATAACGGCCGCAGCACTAATGCGGTTAAAGGGGCTAACAAA
CGCCCTTTAAAATCGCTCAGTGAAATCATTAAAGGCAAGCAGGGGCGTTTCAGGCAAAACCTTTTAGGTAAGCGCGTGGATTTTTCAGGC
AGAAGCGTGATTGTGGTTGGGCCTAATCTCAAAATGGATGAATGCGGGTTGCCTAAAAACATGGCGTTAGAACTCTTCAAACCGCATTTG
TTATCCAAGCTTGAAGAGAGAGGCTATGCCACCACGCTCAAACAGGCTAAACGCATGATTGAGCAAAAAAGCAATGAAGTATGGGAGTGC
TTGCAAGAAATCACAGAGGGGTATCCGGTGCTACTCAACCGCGCTCCTACCTTGCACAAGCAATCCATTCAAGCGTTCCATCCAAAGCTG
ATTGACGGCAAAGCGATCCAATTGCACCCGTTAGTGTGTTCAGCGTTCAACGCCGATTTTGACGGGGACCAAATGGCGGTGCATGTGCCT
TTAAGCCAGGAAGCGATCGCTGAATGCAAGGTGCTGATGCTAAGCTCTATGAATATCCTTTTGCCTGCTAGCGGTAAGGCCGTAGCCATT
CCTAGCCAAGATATGGTTTTAGGGCTTTATTATCTTTCTTTAGAAAAGAGCGGGGTCAAGGGCGAGCATAAGCTTTTTTCTAGCGTGAAT
GAAATCATCACCGCCATTGACACGAAAGAATTAGACATCCACGCAAAGATTAGGGTTTTAGATCAAGGGAATATTATCGCTACGAGTGCA
GGGCGCATGATCATTAAGTCCATTTTGCCTGATTTTATCCCTACGGATTTGTGGAACAGACCCATGAAGAAAAAAGATATTGGCGTGCTT
GTGGATTATGTGCATAAAGTTGGCGGTATCGGTATTACTGCAACCTTTTTGGATAATTTAAAAACGCTTGGCTTTAGGTATGCGACTAAG
GCTGGTATTTCTATCTCTATGGAGGATATTATCACGCCAAAAGACAAGCAAAAAATGGTGGAAAAAGCCAAAGTAGAGGTTAAAAAAATC
CAGCAACAATACGATCAAGGGCTGCTCACTGACCAAGAGCGTTACAATAAGATCATTGACACTTGGACTGAAGTCAATGACAAAATGAGT
AAAGAAATGATGACCGCTATCGCGCAAGATAAAGAGGGCTTTAACTCTATTTATATGATGGCAGATAGCGGCGCAAGGGGTAGCGCGGCG
CAAATCCGTCAGCTTTCAGCGATGAGGGGTCTTATGACAAAGCCGGACGGCAGTATCATTGAAACGCCCATTATTTCTAACTTTAAAGAG
GGGTTGAATGTCTTAGAATACTTCAATTCCACGCATGGCGCTAGAAAGGGCTTAGCGGATACAGCGCTAAAAACAGCCAATGCGGGGTAT
TTGACCAGAAAGCTCATTGATGTTTCGCAAAATGTCAAGGTGGTGTCTGATGATTGCGGCACGCATGAAGGGATTGAAATCACGGATATT
GCGGTGGGGAGTGAGCTGATTGAACCTTTAGAAGAGCGTATTTTTGGGCGCGTTTTATTAGAAGATGTGATCGATCCCATTACGAATGAA
ATCTTGCTTTATGCGGACACTTTGATTGATGAAGAGGGTGCTAAAAAGGTGGTTGAAGCCGGGATTAAATCCATTACGATCCGCACCCCA
GTAACTTGTAAAGCGCCAAAGGGCGTGTGCGCGAAATGCTATGGCTTGAATTTGGGCGAAGGCAAGATGAGTTATCCGGGTGAAGCGGTG
GGCGTGGTAGCCGCGCAATCTATTGGGGAGCCTGGAACGCAGCTCACTTTAAGGACTTTCCATGTGGGCGGGACAGCGAGCAGGAGTCAG
GATGAGCGCGAAATCGTAGCGAGCAAAGAAGGTTTTGTGCGTTTTTACAACCTTAGGACTTACACGAATAAAGAGGGTAAAAACATTATC
GCTAACCGCCGTAACGCTTCTATTTTAGTGGTAGAGCCTAAGATTAAAGCGCCTTTTGATGGGGAATTACGCATTGAAACGGTTTATGAA
GAAGTCGTTGTGAGCGTGAAAAATGGCGATCAAGAAGCTAAATTTGTTTTAAGGAGAAGCGATATTGTCAAGCCAAGCGAATTAGCCGGC
GTTGGCGGTAAGATTGAGGGGAAAGTGTATTTGCCTTATGCTAGTGGGCATAAGGTGCATAAGGGGGGAAGTATCGCTGATATTATCCAA
GAGGGCTGGAATGTGCCTAATCGCATCCCTTATGCGAGCGAATTGCTAGTCAAGGATAATGACCCTATTGCGCAAGATGTGTATGCCAAA
GAAAAAGGCGTAATCAAATACTATGTTTTAGAGGCTAACCATTTAGAGCGCACCCATGGGATCAAAAAGGGCGATATGGTGAGTGAAAAA
GGCTTGTTTGCGGTGATAGCTGATGATAATGGTAGGGAAGCCGCTCGCCATTATATCGCTAGGGGTTCTGAGATCTTGATTGATGATAAT
AGTGAAGTGAGCACTAATAGCGTGATTTCTAAACCCACGACTAACACTTTCAAAACGATTGCCACATGGGATCCTTACAACACCCCTATC
ATTGCGGACTTTAAAGGTAAGGTGGGTTTTGTGGATGTTATCGCAGGGGTTACGGTCGCTGAAAAAGAAGACGAAAATACCGGTATCACA
AGCTTAGTGGTGAATGATTACATTCCAAGCGGATACAAACCAAGCTTGTTTTTAGAGGGGGCTAATGGCGAAGAGATGCGTTATTTCCTA
GAGCCAAAAACCTCTATCGCCATTAGCGATGGCTCTAGCGTGGAGCAAGCTGAAGTGTTAGCGAAAATCCCTAAAGCGACCGTTAAATCT
AGGGATATTACCGGGGGTCTCCCAAGGGTTTCGGAACTCTTTGAAGCGAGAAAACCCAAGCCTAAAGATGTGGCGATCCTTTCTGAAGTT
GATGGGATTGTGAGTTTTGGCAAACCCATTCGCAATAAAGAACACATCATCGTAACTTCTAAAGATGGCCGTTCCATGGATTATTTTGTG
GATAAAGGCAAGCAAATTTTAGTGCATGCCGATGAATTTGTGCATGCGGGAGAAGCGATGACGGACGGAGTAATTTCAAGCCATGATATT
TTAAGGATCAGTGGCGAAAAAGAGCTTTATAAATACATTGTGAGCGAAGTCCAGCAAGTGTATCGCAGGCAGGGGGTGAGCATTGCGGAC
AAGCACATTGAAATCATTGTTTCTCAAATGCTAAGACAGGTGCGTATTTTAGACAGCGGGGATAGCAAGTTTATTGAAGGGGATTTAGTC
AGTAAAAAACTTTTCAAAGAAGAAAACGCTCGTGTGATCGCTTTAAAAGGCGAGCCAGCGATTGCTGAACCGGTGCTTTTAGGGATCACT
AGAGCGGCTATTGGGAGCGATAGCATCATCTCAGCGGCCTCTTTCCAAGAAACGACTAAAGTTTTAACAGAAGCCAGTATCGCTATGAAA
AAAGACTTTTTAGAGGATTTGAAAGAGAATGTGGTGTTGGGGAGGATGATCCCTGTGGGAACAGGCATGTATAAGAATAAAAAAATCGTG
TTAAGAGCGCTTGAGGATAACTCTAAATTTTGA