Genetic determination of the meso-diaminopimelate biosynthetic pathway of mycobacteria

J. D. Cirillo, T. R. Weisbrod, A. Banerjee, B. R. Bloom, W. R. Jacobs

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

The increasing incidence of multiple-drug-resistant mycobacterial infections indicates that the development of new methods for treatment of mycobacterial diseases should be a high priority. meso-Diaminopimelic acid (DAP), a key component of a highly immunogenic subunit of the mycobacterial peptidoglycan layer, has been implicated as a potential virulence factor. The mycobacterial DAP biosynthetic pathway could serve as a target for design of new antimycobacterial agents as well as the construction of in vivo selection systems. We have isolated the asd, dapA, dapB, dapD, and dapE genes involved in the DAP biosynthetic pathway of Mycobacterium bovis BCG. These genes were isolated by complementation of Escherichia coli mutations with an expression library of BCG DNA. Our analysis of these genes suggests that BCG may use more than one pathway for biosynthesis of DAP. The nucleotide sequence of the BCG dapB gene was determined. The activity of the product of this gene in Escherichia coli provided evidence that the gene may encode a novel bifunctional dihydrodipicolinate reductase and DAP dehydrogenase.

Original languageEnglish (US)
Pages (from-to)4424-4429
Number of pages6
JournalJournal of Bacteriology
Volume176
Issue number14
StatePublished - 1994

Fingerprint

Diaminopimelic Acid
Biosynthetic Pathways
Mycobacterium
Mycobacterium bovis
Genes
Dihydrodipicolinate Reductase
Escherichia coli
Peptidoglycan
Virulence Factors
Gene Library
Oxidoreductases
Anti-Bacterial Agents
Mutation
Incidence
Infection
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Applied Microbiology and Biotechnology
  • Immunology

Cite this

Genetic determination of the meso-diaminopimelate biosynthetic pathway of mycobacteria. / Cirillo, J. D.; Weisbrod, T. R.; Banerjee, A.; Bloom, B. R.; Jacobs, W. R.

In: Journal of Bacteriology, Vol. 176, No. 14, 1994, p. 4424-4429.

Research output: Contribution to journalArticle

@article{8c091f551e434d38a04b2c5e73321f34,
title = "Genetic determination of the meso-diaminopimelate biosynthetic pathway of mycobacteria",
abstract = "The increasing incidence of multiple-drug-resistant mycobacterial infections indicates that the development of new methods for treatment of mycobacterial diseases should be a high priority. meso-Diaminopimelic acid (DAP), a key component of a highly immunogenic subunit of the mycobacterial peptidoglycan layer, has been implicated as a potential virulence factor. The mycobacterial DAP biosynthetic pathway could serve as a target for design of new antimycobacterial agents as well as the construction of in vivo selection systems. We have isolated the asd, dapA, dapB, dapD, and dapE genes involved in the DAP biosynthetic pathway of Mycobacterium bovis BCG. These genes were isolated by complementation of Escherichia coli mutations with an expression library of BCG DNA. Our analysis of these genes suggests that BCG may use more than one pathway for biosynthesis of DAP. The nucleotide sequence of the BCG dapB gene was determined. The activity of the product of this gene in Escherichia coli provided evidence that the gene may encode a novel bifunctional dihydrodipicolinate reductase and DAP dehydrogenase.",
author = "Cirillo, {J. D.} and Weisbrod, {T. R.} and A. Banerjee and Bloom, {B. R.} and Jacobs, {W. R.}",
year = "1994",
language = "English (US)",
volume = "176",
pages = "4424--4429",
journal = "Journal of Bacteriology",
issn = "0021-9193",
publisher = "American Society for Microbiology",
number = "14",

}

TY - JOUR

T1 - Genetic determination of the meso-diaminopimelate biosynthetic pathway of mycobacteria

AU - Cirillo, J. D.

AU - Weisbrod, T. R.

AU - Banerjee, A.

AU - Bloom, B. R.

AU - Jacobs, W. R.

PY - 1994

Y1 - 1994

N2 - The increasing incidence of multiple-drug-resistant mycobacterial infections indicates that the development of new methods for treatment of mycobacterial diseases should be a high priority. meso-Diaminopimelic acid (DAP), a key component of a highly immunogenic subunit of the mycobacterial peptidoglycan layer, has been implicated as a potential virulence factor. The mycobacterial DAP biosynthetic pathway could serve as a target for design of new antimycobacterial agents as well as the construction of in vivo selection systems. We have isolated the asd, dapA, dapB, dapD, and dapE genes involved in the DAP biosynthetic pathway of Mycobacterium bovis BCG. These genes were isolated by complementation of Escherichia coli mutations with an expression library of BCG DNA. Our analysis of these genes suggests that BCG may use more than one pathway for biosynthesis of DAP. The nucleotide sequence of the BCG dapB gene was determined. The activity of the product of this gene in Escherichia coli provided evidence that the gene may encode a novel bifunctional dihydrodipicolinate reductase and DAP dehydrogenase.

AB - The increasing incidence of multiple-drug-resistant mycobacterial infections indicates that the development of new methods for treatment of mycobacterial diseases should be a high priority. meso-Diaminopimelic acid (DAP), a key component of a highly immunogenic subunit of the mycobacterial peptidoglycan layer, has been implicated as a potential virulence factor. The mycobacterial DAP biosynthetic pathway could serve as a target for design of new antimycobacterial agents as well as the construction of in vivo selection systems. We have isolated the asd, dapA, dapB, dapD, and dapE genes involved in the DAP biosynthetic pathway of Mycobacterium bovis BCG. These genes were isolated by complementation of Escherichia coli mutations with an expression library of BCG DNA. Our analysis of these genes suggests that BCG may use more than one pathway for biosynthesis of DAP. The nucleotide sequence of the BCG dapB gene was determined. The activity of the product of this gene in Escherichia coli provided evidence that the gene may encode a novel bifunctional dihydrodipicolinate reductase and DAP dehydrogenase.

UR - http://www.scopus.com/inward/record.url?scp=0028233325&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028233325&partnerID=8YFLogxK

M3 - Article

C2 - 8021227

AN - SCOPUS:0028233325

VL - 176

SP - 4424

EP - 4429

JO - Journal of Bacteriology

JF - Journal of Bacteriology

SN - 0021-9193

IS - 14

ER -