Database Authors
Carol A Fulcher1, Ron Caspi1, Markus Krummenacker1, Suzanne Paley1, Anamika Kothari1, Maneesh Yadav1, Ingrid Keseler1, Peter D Karp1, Amanda Mackie2, Brendan Wilson-Mortier2, Anahit Penesyan2, Ian Paulsen2
1SRI International, 2Macquarie University
Summary In the last 200 years, tuberculosis (TB) has been responsible for the deaths of over 1 billion people [Gagneux18]. More recently, after briefly falling behind COVID-19, TB has regained its title as the world's deadliest infectious disease [Ilic23, Orgeur24]. According to the World Health Organisation, in 2022, 10.6 million people around the world fell ill with this potentially deadly respiratory disease, and 1.3 million lost their lives [Orgeur24]. Originally named "tubercle bacillus" by German physician and microbiologist Robert Koch upon isolation in 1882, the etiological agent of TB is the actinobacterium Mycobacterium tuberculosis [Sakula83].

Mycobacterium tuberculosis is part of the Mycobacterium tuberculosis complex (MTBC), a group of highly related mycobacteria (>99% nucleotide sequence identity) with lineages adapted to causing disease in both humans and also wild and domestic animals [Gagneux18]. M. tuberculosis is characterized by qualities such as its persistence within alveolar macrophages, slow growth, ability to enter dormancy, complex cell envelope and evasion of host immunity [McDonough93, Cole98, Meena10, Rahlwes23, Bo23]. Unfortunately, this pathogen has also exhibited both multidrug resistance (MDR-TB) and extensive drug resistance (XDR-TB) [Gagneux18, Rahlwes23].

The genome represented by this PGDB belongs to Mycobacterium tuberculosis H37Rv. This strain and its avirulent counterpart, Mycobacterium tuberculosis H37Ra, are derivatives of M. tuberculosis H37, which was first isolated from the sputum of a 19 year old patient with chronic pulmonary tuberculosis at Saranac laboratory in 1905 [Steenken34, Santoro17]. The genome of M. tuberculosis H37Rv was first sequenced in 1998, and has since become the reference genome for members of the MTBC, undergoing subsequent re-annotation and resequencing to improve mycobacterial research efforts [Cole98, Camus02, Chitale22]. This PGDB has been extensively updated via manual curation. In addition, we have incorporated large datasets into the database characterizing the transcriptional regulatory network [Rustad14, Turkarslan15, Minch15], transcription start sites [Cortes13, Shell15], small RNAs [Stiens23, Miotto12], gene essentiality [DeJesus17], as well as information on anti-tuberculosis compounds.

This Pathway/Genome Database (PGDB) was generated on 19-Nov-2015 from Genbank record AL123456.3 by the PathoLogic component of Pathway Tools software version 20.0 and MetaCyc version 19.6 [Karp10, Caspi14].

We thank Professor Dirk Schnappinger (Weill Cornell Medical College) and Professor Thomas R. Ioerger (Texas A&M University) for their assistance in identifying recent advancements in M. tuberculosis research and relevant data collections for this PGDB.

Genome
RepliconTotal GenesProtein GenesRNA GenesPseudogenesSize (bp)NCBI Link
Chromosome5,6073,9921,615134,411,532RefSeq:AL123456
Ortholog data available?Yes
Database Contents
Genes5,607
Pathways291
Enzymatic Reactions1,819
Transport Reactions59
Polypeptides4,018
Protein Complexes175
Enzymes1,113
Transporters182
Compounds1,981
Transcription Units3,734
tRNAs45
Growth Media4
Transcriptional Regulation4,117
Protein Features13,634
GO Annotations60,530
Gene Essentiality Datasets4
Database Version29.6
Image of Mycobacterium tuberculosis cells
Image of Mycobacterium tuberculosis cells, provided by the National Institute of Allergy and Infectious Diseases (NIAID). Used under creative commons license.
Taxonomic Lineage cellular organisms
Bacteria <bacteria>
Bacillati
Actinomycetota
Actinomycetes
Mycobacteriales
Mycobacteriaceae
Mycobacterium
Mycobacterium tuberculosis complex
Mycobacterium tuberculosis
Mycobacterium tuberculosis H37Rv
Genetic Code Number 11 -- Bacterial, Archaeal and Plant Plastid (same as Standard, except for alternate initiation codons)
NCBI BioProjectPRJNA224
NCBI-Taxonomy83332
Relationship to Oxygenaerobe
Trophic Levelheterotroph
Temperature Rangemesophile
Pathogenicityanimal
NCBI Genome Typereference
Copyright 2018, SRI International. All Rights Reserved.

References

Bo23: Bo H, Moure UAE, Yang Y, Pan J, Li L, Wang M, Ke X, Cui H (2023). "Mycobacterium tuberculosis -macrophage interaction: Molecular updates." Front Cell Infect Microbiol 13;1062963. PMID: 36936766

Camus02: Camus JC, Pryor MJ, Medigue C, Cole ST (2002). "Re-annotation of the genome sequence of Mycobacterium tuberculosis H37Rv." Microbiology 148(Pt 10);2967-73. PMID: 12368430

Caspi14: Caspi R, Altman T, Billington R, Dreher K, Foerster H, Fulcher CA, Holland TA, Keseler IM, Kothari A, Kubo A, Krummenacker M, Latendresse M, Mueller LA, Ong Q, Paley S, Subhraveti P, Weaver DS, Weerasinghe D, Zhang P, Karp PD (2014). "The MetaCyc database of metabolic pathways and enzymes and the BioCyc collection of Pathway/Genome Databases." Nucleic Acids Res. 42(1):D459-D471. PMID: 24225315

Chitale22: Chitale P, Lemenze AD, Fogarty EC, Shah A, Grady C, Odom-Mabey AR, Johnson WE, Yang JH, Eren AM, Brosch R, Kumar P, Alland D (2022). "A comprehensive update to the Mycobacterium tuberculosis H37Rv reference genome." Nat Commun 13(1);7068. PMID: 36400796

Cole98: Cole ST, Brosch R, Parkhill J, Garnier T, Churcher C, Harris D, Gordon SV, Eiglmeier K, Gas S, Barry CE, Tekaia F, Badcock K, Basham D, Brown D, Chillingworth T, Connor R, Davies R, Devlin K, Feltwell T, Gentles S, Hamlin N, Holroyd S, Hornsby T, Jagels K, Krogh A, McLean J, Moule S, Murphy L, Oliver K, Osborne J, Quail MA, Rajandream MA, Rogers J, Rutter S, Seeger K, Skelton J, Squares R, Squares S, Sulston JE, Taylor K, Whitehead S, Barrell BG (1998). "Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence." Nature 393(6685);537-44. PMID: 9634230

Cortes13: Cortes T, Schubert OT, Rose G, Arnvig KB, Comas I, Aebersold R, Young DB (2013). "Genome-wide mapping of transcriptional start sites defines an extensive leaderless transcriptome in Mycobacterium tuberculosis." Cell Rep 5(4);1121-31. PMID: 24268774

DeJesus17: DeJesus MA, Gerrick ER, Xu W, Park SW, Long JE, Boutte CC, Rubin EJ, Schnappinger D, Ehrt S, Fortune SM, Sassetti CM, Ioerger TR (2017). "Comprehensive Essentiality Analysis of the Mycobacterium tuberculosis Genome via Saturating Transposon Mutagenesis." mBio 8(1). PMID: 28096490

Gagneux18: Gagneux S (2018). "Ecology and evolution of Mycobacterium tuberculosis." Nat Rev Microbiol 16(4);202-213. PMID: 29456241

Ilic23: Ilic M, Bjelic D, Javorac J, Tot Veres K, Zivanovic D, Kovacevic D, Maric N, Lalic N, Colic N, Stjepanovic M (2023). "Knowledge is the most powerful tool in the fight against tuberculosis." J Infect Dev Ctries 17(8);1099-1106. PMID: 37699089

Karp10: Karp PD, Paley SM, Krummenacker M, Latendresse M, Dale JM, Lee TJ, Kaipa P, Gilham F, Spaulding A, Popescu L, Altman T, Paulsen I, Keseler IM, Caspi R (2010). "Pathway Tools version 13.0: integrated software for pathway/genome informatics and systems biology." Brief Bioinform 11(1);40-79. PMID: 19955237

McDonough93: McDonough KA, Kress Y, Bloom BR (1993). "Pathogenesis of tuberculosis: interaction of Mycobacterium tuberculosis with macrophages." Infect Immun 61(7);2763-73. PMID: 8514378

Meena10: Meena LS, Rajni (2010). "Survival mechanisms of pathogenic Mycobacterium tuberculosis H37Rv." FEBS J 277(11);2416-27. PMID: 20553485

Minch15: Minch KJ, Rustad TR, Peterson EJ, Winkler J, Reiss DJ, Ma S, Hickey M, Brabant W, Morrison B, Turkarslan S, Mawhinney C, Galagan JE, Price ND, Baliga NS, Sherman DR (2015). "The DNA-binding network of Mycobacterium tuberculosis." Nat Commun 6;5829. PMID: 25581030

Miotto12: Miotto P, Forti F, Ambrosi A, Pellin D, Veiga DF, Balazsi G, Gennaro ML, Di Serio C, Ghisotti D, Cirillo DM (2012). "Genome-wide discovery of small RNAs in Mycobacterium tuberculosis." PLoS One 7(12);e51950. PMID: 23284830

Orgeur24: Orgeur M, Sous C, Madacki J, Brosch R (2024). "Evolution and emergence of Mycobacterium tuberculosis." FEMS Microbiol Rev 48(2). PMID: 38365982

Rahlwes23: Rahlwes KC, Dias BRS, Campos PC, Alvarez-Arguedas S, Shiloh MU (2023). "Pathogenicity and virulence of Mycobacterium tuberculosis." Virulence 14(1);2150449. PMID: 36419223

Rustad14: Rustad TR, Minch KJ, Ma S, Winkler JK, Hobbs S, Hickey M, Brabant W, Turkarslan S, Price ND, Baliga NS, Sherman DR (2014). "Mapping and manipulating the Mycobacterium tuberculosis transcriptome using a transcription factor overexpression-derived regulatory network." Genome Biol 15(11);502. PMID: 25380655

Sakula83: Sakula A (1983). "Robert koch: centenary of the discovery of the tubercle bacillus, 1882." Can Vet J 24(4);127-31. PMID: 17422248

Santoro17: Santoro F, Guerrini V, Lazzeri E, Iannelli F, Pozzi G (2017). "Genomic polymorphisms in a Laboratory Isolate of Mycobacterium tuberculosis Reference Strain H37Rv (ATCC27294)." New Microbiol 40(1);62-69. PMID: 27819398

Shell15: Shell SS, Wang J, Lapierre P, Mir M, Chase MR, Pyle MM, Gawande R, Ahmad R, Sarracino DA, Ioerger TR, Fortune SM, Derbyshire KM, Wade JT, Gray TA (2015). "Leaderless Transcripts and Small Proteins Are Common Features of the Mycobacterial Translational Landscape." PLoS Genet 11(11);e1005641. PMID: 26536359

Steenken34: Steenken W, Oatway WH, Petroff SA (1934). "BIOLOGICAL STUDIES OF THE TUBERCLE BACILLUS : III. DISSOCIATION AND PATHOGENICITY OF THE R AND S VARIANTS OF THE HUMAN TUBERCLE BACILLUS (H(37))." J Exp Med 60(4);515-40. PMID: 19870319

Stiens23: Stiens J, Tan YY, Joyce R, Arnvig KB, Kendall SL, Nobeli I (2023). "Using a whole genome co-expression network to inform the functional characterisation of predicted genomic elements from Mycobacterium tuberculosis transcriptomic data." Mol Microbiol 119(4);381-400. PMID: 36924313

Turkarslan15: Turkarslan S, Peterson EJ, Rustad TR, Minch KJ, Reiss DJ, Morrison R, Ma S, Price ND, Sherman DR, Baliga NS (2015). "A comprehensive map of genome-wide gene regulation in Mycobacterium tuberculosis." Sci Data 2;150010. PMID: 25977815

References

Ekins13: Ekins S, Clark AM, Sarker M (2013). "TB Mobile: a mobile app for anti-tuberculosis molecules with known targets." J Cheminform 5(1);13. PMID: 23497706


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