Review on Mycobacterial Metabolic Pathways as Drug Targets

Review on Mycobacterial Metabolic Pathways as Drug Targets

Feyera Gemeda Dima

Contact

Ebsa Bushura

Contact

Jimma University

Review on Mycobacterial Metabolic Pathways as Drug Targets

Article Fingerprint

ReserarchID

46T34

Review on Mycobacterial Metabolic Pathways as Drug Targets Banner

AI TAKEAWAY

Connecting with the Eternal Ground

Abstract

Mycobacterium is acid fast genus of bacteria that include many pathogenic and non pathogenic species. Tuberculosis (TB) is the leading cause of death in the world from a bacterial infectious disease. The emergence of antibiotic resistance strains has raised the need towards the development of new antibiotics or drug molecules which can kill or suppress the growth of pathogenic Mycobacterium species. The increasing emergence of drug-resistant tuberculosis along with the HIV pandemic (human) threatens disease control and highlights both the need to understand how our current drugs work and the need to develop new and more effective drugs. Novel efforts in developing drugs that target the intracellular metabolism of M. tuberculosis often focus on metabolic pathways that are specific to mycobacterium. Potential drug targets were also identified from pathways related to lipid metabolism, carbohydrate metabolism, amino acid metabolism, energy metabolism, vitamin and cofactor biosynthetic pathways and nucleotide metabolism. Approximately one-fourth of the Mycobacterium tuberculosis genome contains genes that encode proteins directly involved in its metabolism. This review provides a brief historical account of tuberculosis drugs, metabolic pathways, examines the problem of current chemotherapy, discusses the targets of current tuberculosis drugs with focuses on some metabolic pathways. The identification of drug target form that unique metabolism of mycobacterium is crutial to to develop new drug for persistent and latent infection of tuberculosis.

References

82 Cites in Article

Reference Format

Lefa Alksne,Steven Projan (2000). Bacterial virulence as a target for antimicrobial chemotherapy.
Asad Amir,Khyati Rana,Arvind Arya,Neelesh Kapoor,Hirdesh Kumar,Mohd Asif Siddiqui (2014). mycobacterium tuberculosis h37rv: in silico drug targets identification by metabolic pathways analysis Department of Biotechnology.
Ritu Bansal-Mutalik,Hiroshi Nikaido (2014). Mycobacterial outer membrane is a lipid bilayer and the inner membrane is unusually rich in diacyl phosphatidylinositol dimannosides.
J Barrett,R Goldschmidt,L Lawrence,B Foleno,R Chen (1998). Antibacterial agents that inhibit two component signal transduction systems.
C Barry,D Crick,M Mcneil (2007). Targeting the formation of the cell wall core of M. tuberculosis.
Joanna Betts,Pauline Lukey,Linda Robb,Ruth Mcadam,Ken Duncan (2002). Evaluation of a nutrient starvation model of Mycobacterium tuberculosis persistence by gene and protein expression profiling.
Joanna Betts,Alistair Mclaren,Mark Lennon,Fiona Kelly,Pauline Lukey,Steve Blakemore,Ken Duncan (2003). Signature Gene Expression Profiles Discriminate between Isoniazid-, Thiolactomycin-, and Triclosan-Treated Mycobacterium tuberculosis.
H Blumberg (2003). American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America.
Calvin Boon,Thomas Dick (2002). Mycobacterium bovisBCG Response Regulator Essential for Hypoxic Dormancy.
V Braun,K Hantke,W Koster (1998). Bacterial iron transport: mechanisms genetics, and regulation.
Roland Brosch,Stephen Gordon,Thierry Garnier,Karin Eiglmeier,Wafa Frigui,Philippe Valenti,Sandrine Dos Santos,Stéphanie Duthoy,Céline Lacroix,Carmen Garcia-Pelayo,Jacqueline Inwald,Paul Golby,Javier Garcia,R Hewinson,Marcel Behr,Michael Quail,Carol Churcher,Bart Barrell,Julian Parkhill,Stewart Cole (2007). Genome plasticity of BCG and impact on vaccine efficacy.
Nancy Buchmeier,Anne Blanc‐potard,Sabine Ehrt,Debra Piddington,Lee Riley,Eduardo Groisman (2000). A parallel intraphagosomal survival strategy shared by Mycobacterium tuberculosis and Salmonella enterica.
Edward Chan,Valerie Laurel,Matthew Strand,Julanie Chan,Mai-Lan N. Huynh,Marian Goble,Michael Iseman (2004). Treatment and Outcome Analysis of 205 Patients with Multidrug-resistant Tuberculosis.
I Chopra,L Hesse,A O'neill (2002). Exploiting current understanding of antibiotic action for discovery of new drugs.
J Christopher,M Niederweis (2011). Mycobacterium tuber culosis Can Utilize Heme as an Iron Source.
S Cole (2002). Comparative mycobacterial genomics as a tool for drug target and antigen discovery.
S Cole,R Brosch,J Parkhill,T Garnier,C Churcher,D Harris,S Gordon,K Eiglmeier,S Gas,C Barry,F Tekaia,K Badcock,D Basham,D Brown,T Chillingworth,R Connor,R Davies,K Devlin,T Feltwell,S Gentles,N Hamlin,S Holroyd,T Hornsby,K Jagels,A Krogh,J Mclean,S Moule,L Murphy,K Oliver,J Osborne,M Quail,M-A Rajandream,J Rogers,S Rutter,K Seeger,J Skelton,R Squares,S Squares,J Sulston,K Taylor,S Whitehead,B Barrell (1998). Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence.
John Dahl,Carl Kraus,Helena Boshoff,Bernard Doan,Korrie Foley,David Avarbock,Gilla Kaplan,Valerie Mizrahi,Harvey Rubin,Clifton Barry (2003). The role of Rel Mtb -mediated adaptation to stationary phase in long-term persistence of Mycobacterium tuberculosis in mice.
N Dasgupta,V Kapur,K Singh,T Das,S Sachdeva,K Jyothisri,J Tyagi (2000). Characterization of a two-component system, devR-devS, of Mycobacterium tuberculosis.
Manjula Datta,M Radhamani,R Selvaraj,C Paramasivan,B Gopalan,C Sudeendra,R Prabhakar (1993). Critical assessment of smear-positive pulmonary tuberculosis patients after chemotherapy under the district tuberculosis programme.
G De Lisle,C Mackintosh,J Schlundt (2001). Mycobacterium bovis in a free-living and captive wildlife, including farmed deer.
De Voss,J Rutter,K Schroeder,B Su,H Zhu,Y Barry,E (2000). The salicylatederived mycobactin siderophores of Mycobacterium tuberculosis are essential for growth in macrophages.
O Devergne,D Emilie,M Peuchmaur,M Crevon,M D'agay,P Galanaud (1992). Production of cytokines in sarcoid lymph nodes: Preferential expression of interleukin-1β and interferon-γ genes.
Thomas Dougherty,John Barrett,Michael Pucci (2002). Microbial Genomics and Novel Antibiotic Discovery: New Technology to Search for New Drugs.
Gael Fenhalls,Liesel Stevens,Lorraine Moses,Juanita Bezuidenhout,Joanna Betts,Paul Helden,Pauline Lukey,Ken Duncan (2002). In Situ Detection of Mycobacterium tuberculosis Transcripts in Human Lung Granulomas Reveals Differential Gene Expression in Necrotic Lesions.
Robert Fleischmann,Mark Adams,Owen White,Rebecca Clayton,Ewen Kirkness,Anthony Kerlavage,Carol Bult,Jean-Francois Tomb,Brian Dougherty,Joseph Merrick,Keith Mckenney,Granger Sutton,Will Fitzhugh,,Chris Fields,Jeannine Gocayne,John Scott,Robert Shirley,Li-Lng Liu,Anna Glodek,Jenny Kelley,Janice Weidman,Cheryl Phillips,Tracy Spriggs,Eva Hedblom,Matthew Cotton,Teresa Utterback,Michael Hanna,David Nguyen,Deborah Saudek,Rhonda Brandon,Leah Fine,Janice Fritchman,Joyce Fuhrmann,N Geoghagen,Cheryl Gnehm,Lisa Mcdonald,Keith Small,Claire Fraser,Hamilton Smith,J Venter (1995). Whole-Genome Random Sequencing and Assembly of Haemophilus influenzae Rd.
Eric Forget,Dick Menzies (2006). Adverse reactions to first-line antituberculosis drugs.
Michael Galperin,Eugene Koonin (1999). Searching for drug targets in microbial genomes.
Robert Garvin,Debajit Biswas,Luigi Gorini (1974). The Effects of Streptomycin or Dihydrostreptomycin Binding to 16S RNA or to 30S Ribosomal Subunits.
Gic) (2001). Erratum: Initial sequencing and analysis of the human genome.
Michael Glickman,Jeffery Cox,William Jacobs (2000). A Novel Mycolic Acid Cyclopropane Synthetase Is Required for Cording, Persistence, and Virulence of Mycobacterium tuberculosis.
Michael Glickman,William Jacobs (2001). Microbial Pathogenesis of Mycobacterium tuberculosis: Dawn of a Discipline.
Gaftdd) (2001). Global Alliance for Tuberculosis Drug Development (TB Alliance).
R Hider,X Kong (2010). Chemistry and biology of siderophores.
J Hoch (2000). Two component and phosphorelay signal transduction.
Paul Jones,Nikki Parrish,Todd Houston,Anthony Stapon,Niharika Bansal,James Dick,Craig Townsend (2000). A New Class of Antituberculosis Agents.
M Kanehisa,S Goto,S Kawashima,A Nakaya (2002). The KEGG databases at GenomeNet.
M Kimerling,H Kluge,N Vezhnina,T Iacovazzi,T Demeulenaere,F Portaels (1999). Inadequacy of the current WHO retreatment regimen in a central Siberian prison: treatment failure and MDR-TB.
P Kolattukudy,N Fernandes,A Azad,A Fitzmaurice,T Sirakova (1997). Biochemistry and molecular genetics of cell-wall lipid biosynthesis in mycobacteria.
G Kontoghiorghes,E Weinberg (1995). Iron: Mammalian defense systems, mechanisms of disease, and chelation therapy approaches.
Lamichhane (2005). Designer arrays for defined mutant analysis to detect genes essential for survival of Mycobacterium tuberculosis in mouse lungs.
Pierre Lemagueres,Hookang Im,Jerry Ebalunode,Ulrich Strych,Michael Benedik,James Briggs,Harold Kohn,Kurt Krause (2005). The 1.9 Å Crystal Structure of Alanine Racemase from Mycobacterium tuberculosis Contains a Conserved Entryway into the Active Site,.
E Luis,S Jason,A Thomas,H Paul,T Christopher (1998). Identification of a Mycobacterium tuberculosis gene cluster encoding the biosynthetic enzymes for assembly of the virulence conferring siderophore mycobactin.
Yufang Ma,Richard Stern,Michael Scherman,Varalakshmi Vissa,Wenxin Yan,Victoria Jones,Fangqiu Zhang,Scott Franzblau,Walter Lewis,Michael Mcneil (2001). Drug Targeting Mycobacterium tuberculosis Cell Wall Synthesis: Genetics of dTDP-Rhamnose Synthetic Enzymes and Development of a Microtiter Plate-Based Screen for Inhibitors of Conversion of dTDP-Glucose to dTDP-Rhamnose.
Courtney Maus,Bonnie Plikaytis,Thomas Shinnick (2005). Mutation of tlyA Confers Capreomycin Resistance in Mycobacterium tuberculosis.
W Mcdermott (2000). Microbial persistence.
John Mckinney,Kerstin Zu Bentrup,Ernesto Muñoz-Elías,Andras Miczak,Bing Chen,Wai-Tsing Chan,Dana Swenson,James Sacchettini,William Jacobs,David Russell (2000). Persistence of Mycobacterium tuberculosis in macrophages and mice requires the glyoxylate shunt enzyme isocitrate lyase.
K Mikusova,M Mikus,G Besra,I Hannock,P Brennan (1996). Chemistry of the bacterial cell wall.
K Mikusova,R Slayden,G Besra,P Brennan (1995). Biogenesis of the mycobacterial cell wall and the site of action of ethambutol.
Seyed Mirsaeidi,Payam Tabarsi,Kaveh Khoshnood,Majid Pooramiri,Ali Rowhani-Rahbar,Seyed Mansoori,Heydar Masjedi,Soheyla Zahirifard,Foroozan Mohammadi,Parisa Farnia,Mohammad Masjedi,Ali Velayati (2005). Treatment of multiple drug-resistant tuberculosis (MDR-TB) in Iran.
Jean Nachega,Richard Chaisson (2003). Tuberculosis Drug Resistance: A Global Threat.
R Newton (1975). Side effects of drugs used to treat tuberculosis.
Heui‐dong Park,Kristi Guinn,Maria Harrell,Reiling Liao,Martin Voskuil,Martin Tompa,Gary Schoolnik,David Sherman (2003). Rv3133c/dosR is a transcription factor that mediates the hypoxic response of Mycobacterium tuberculosis.
N Parrish,F Kuhajda,H Heine,W Bishai,J Dick (1999). Antimycobacterial activity of cerulenin and its effects on lipid biosynthesis.
Esther Pérez,Sofía Samper,Yann Bordas,Christophe Guilhot,Brigitte Gicquel,Carlos Martín (2001). An essential role for phoP in Mycobacterium tuberculosis virulence.
Robert Rando (1975). On the mechanism of action of antibiotics which act as irreversible enzyme inhibitors.
Musa Sani,Edith Houben,Jeroen Geurtsen,Jason Pierson,Karin De Punder,Maaike Van Zon,Brigitte Wever,Sander Piersma,Connie Jiménez,Mamadou Daffé,Ben Appelmelk,Wilbert Bitter,Nicole Van Der Wel,Peter Peters (2010). Direct Visualization by Cryo-EM of the Mycobacterial Capsular Layer: A Labile Structure Containing ESX-1-Secreted Proteins.
Christopher Sassetti,Dana Boyd,Eric Rubin (2003). Genes required for mycobacterial growth defined by high density mutagenesis.
Christopher Sassetti,Eric Rubin (2003). Genetic requirements for mycobacterial survival during infection.
Mark Schena,Dari Shalon,Ronald Davis,Patrick Brown (1995). Quantitative Monitoring of Gene Expression Patterns with a Complementary DNA Microarray.
G Schuller-Levis,W Levis,M Ammazzalorso,A Nosrati,E Park (1994). Mycobacterial lipoarabinomannan induces nitric oxide and tumor necrosis factor alpha production in a macrophage cell line: down regulation by taurine chloramine.
R Slayden,R Lee,J Armour,A Cooper,I Orme,P Brennan,G Besra (1996). Antimycobacterial action of thiolactomycin: an inhibitor of fatty acid and mycolic acid synthesis.
Ulrich Strych,Rebecca Penland,Margarita Jimenez,Kurt Krause,Michael Benedik (2001). Characterization of the alanine racemases from two Mycobacteria.
Sunny Jalhan (2013). Review on current trends and advancement in drugs Trends and drug targets for tuberculosis therapy. new drug trends in tuberculosis ,international journal of pharma and bio sciences.
K Kilburn,J (1989). Inhibition of synthesis of arabinogalactan by ethambutol in Mycobacterium smegmatis.
Roman Tatusov,Natalie Fedorova,John Jackson,Aviva Jacobs,Boris Kiryutin,Eugene Koonin,Dmitri Krylov,Raja Mazumder,Sergei Mekhedov,Anastasia Nikolskaya,B Rao,Sergei Smirnov,Alexander Sverdlov,Sona Vasudevan,Yuri Wolf,Jodie Yin,Darren Natale (2003). The COG database: an updated version includes eukaryotes.
Martin Voskuil,Dirk Schnappinger,Kevin Visconti,Maria Harrell,Gregory Dolganov,David Sherman,Gary Schoolnik (2003). Inhibition of Respiration by Nitric Oxide Induces aMycobacterium tuberculosisDormancy Program.
L Wayne,L Hayes (1996). An in vitro model for sequential study of shiftdown of Mycobacterium tuberculosis through two stages of nonreplicating persistence.
L Waynes,L Haynes (1998). Nitrate reduction as a marker for hypoxic shift down of Mycobacterium tuberculosis.
L Waynes,K Lin (1982). Glyoxylate metabolism and adaptation of Mycobacterium tuberculosis to survival under anaerobic conditions.
Michael Wilson,Joseph Derisi,Hans-Henrik Kristensen,Paul Imboden,Sangeeta Rane,Patrick Brown,Gary Schoolnik (1999). Exploring drug-induced alterations in gene expression in Mycobacterium tuberculosis by microarray hybridization.
F Winder,P Collins (1970). Inhibition by Isoniazid of Synthesis of Mycolic Acids in Mycobacterium tuberculosis.
(2003). Tuberculosis Voices of the Unheard / World Health Organization (WHO)..
W Yew,C Wong,P Wong,J Lee,C Chau (1993). Adverse neurological reactions in patients with multi-drug resistant pulmonary tuberculosis after co-administration of cycloserine and ofloxacin.
T Zahrt,V Deretic (2000). An essential two component signal transduction system in Mycobacterium tuberculosis.
Y Zhang (2003). Mode of action of pyrazinamide: disruption of membrane potential and transport by pyrazinamide.
Ying Zhang (2004). Persistent and dormant tubercle bacilli and latent tuberculosis.
Ying Zhang (2005). THE MAGIC BULLETS AND TUBERCULOSIS DRUG TARGETS.
Y Zhang,L Amzel (2002). Tuberculosis drug targets.
Ying Zhang,Beate Heym,Bryan Allen,Douglas Young,Stewart Cole (1992). The catalase—peroxidase gene and isoniazid resistance of Mycobacterium tuberculosis.
Ying Zhang,Zhonghe Sun,Sallie Permar (2002). Conditions that may affect the results of susceptibility testing of Mycobacterium tuberculosis to pyrazinamide.
Y Zhang,A Telenti,G Hatfull,W Jacobs (2000). Molecular Genetics of Mycobacteria.

Download References

Funding

No external funding was declared for this work.

Conflict of Interest

The authors declare no conflict of interest.

Ethical Approval

No ethics committee approval was required for this article type.

Data Availability

Not applicable for this article.

How to Cite This Article

Feyera Gemeda Dima. 2018. \u201cReview on Mycobacterial Metabolic Pathways as Drug Targets\u201d. Global Journal of Medical Research - C: Microbiology & Pathology GJMR-C Volume 18 (GJMR Volume 18 Issue C1).

More Citation Formats

Select Citation Style:

Download Citation

GJMR Volume 18 Issue C1

Explore Journals Explore Volume Read This Issue

Journal Specifications

Crossref Journal DOI 10.17406/gjmra

Print ISSN 0975-5888

e-ISSN 2249-4618

Keywords

Not Found

Classification

GJMR-C Classification NLMC Code: QW 125.5.M9

Submission ReceivedDecember 8, 2017
Peer Review Double Blind
Handling Editor
Accepted January 2, 2018
Published January 15, 2018

Version of record

v1.2

Issue date

July 30, 2018

Language

Experiance in AR

Explore published articles in an immersive Augmented Reality environment. Our platform converts research papers into interactive 3D books, allowing readers to view and interact with content using AR and VR compatible devices.

View in VR

Read in 3D

Your published article is automatically converted into a realistic 3D book. Flip through pages and read research papers in a more engaging and interactive format.

View in 3D

Article Matrices

Total Score: 72

Country: Ethiopia

Subject: Global Journal of Medical Research - C: Microbiology & Pathology

Authors: Ebsa Bushura, Feyera Gemeda Dima (PhD/Dr. count: 0)

View Count (all-time): 184

Total Views (Real + Logic): 2953

Total Downloads (simulated): 1492

Publish Date: 2018 07, Mon

Monthly Totals (Real + Logic):

Month 1: 28 views
Month 2: 54 views
Month 3: 59 views
Month 4: 47 views
Month 5: 39 views
Month 6: 47 views
Month 7: 27 views
Month 8: 58 views
Month 9: 23 views
Month 10: 25 views
Month 11: 36 views
Month 12: 45 views
Month 13: 27 views
Month 14: 46 views
Month 15: 16 views
Month 16: 35 views
Month 17: 29 views
Month 18: 24 views
Month 19: 22 views
Month 20: 23 views
Month 21: 29 views
Month 22: 26 views
Month 23: 18 views
Month 24: 44 views
Month 25: 19 views
Month 26: 33 views
Month 27: 28 views
Month 28: 41 views
Month 29: 43 views
Month 30: 27 views
Month 31: 43 views
Month 32: 40 views
Month 33: 38 views
Month 34: 37 views
Month 35: 23 views
Month 36: 30 views
Month 37: 37 views
Month 38: 14 views
Month 39: 14 views
Month 40: 25 views
Month 41: 45 views
Month 42: 18 views
Month 43: 43 views
Month 44: 25 views
Month 45: 32 views
Month 46: 18 views
Month 47: 17 views
Month 48: 25 views
Month 49: 29 views
Month 50: 21 views
Month 51: 43 views
Month 52: 29 views
Month 53: 26 views
Month 54: 36 views
Month 55: 27 views
Month 56: 47 views
Month 57: 37 views
Month 58: 27 views
Month 59: 20 views
Month 60: 42 views
Month 61: 19 views
Month 62: 30 views
Month 63: 15 views
Month 64: 35 views
Month 65: 32 views
Month 66: 39 views
Month 67: 16 views
Month 68: 14 views
Month 69: 28 views
Month 70: 20 views
Month 71: 49 views
Month 72: 16 views
Month 73: 17 views
Month 74: 29 views
Month 75: 31 views
Month 76: 44 views
Month 77: 20 views
Month 78: 22 views
Month 79: 17 views
Month 80: 23 views
Month 81: 27 views
Month 82: 33 views
Month 83: 16 views
Month 84: 18 views
Month 85: 25 views
Month 86: 37 views
Month 87: 16 views
Month 88: 17 views
Month 89: 21 views
Month 90: 42 views
Month 91: 47 views
Month 92: 36 views
Month 93: 46 views

Total Views: 2953

Total Downloads: 1492

2026 Trends

Our website is actively being updated, and changes may occur frequently. Please clear your browser cache if needed. For feedback or error reporting, please email [email protected]