Affiliation:
1. School of Biosciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, United Kingdom
Abstract
ABSTRACT
The cell wall of
Mycobacterium tuberculosis
is unique in that it differs significantly from those of both Gram-negative and Gram-positive bacteria. The thick, carbohydrate- and lipid-rich cell wall with distinct lipoglycans enables mycobacteria to survive under hostile conditions such as shortage of nutrients and antimicrobial exposure. The key features of this highly complex cell wall are the mycolyl-arabinogalactan-peptidoglycan (mAGP)–based and phosphatidyl-
myo
-inositol–based macromolecular structures, with the latter possessing potent immunomodulatory properties. These structures are crucial for the growth, viability, and virulence of
M. tuberculosis
and therefore are often the targets of effective chemotherapeutic agents against tuberculosis. Over the past decade, sophisticated genomic and molecular tools have advanced our understanding of the primary structure and biosynthesis of these macromolecules. The availability of the full genome sequences of various mycobacterial species, including
M. tuberculosis
,
Mycobacterium marinum
, and
Mycobacterium bovis
BCG, have greatly facilitated the identification of large numbers of drug targets and antigens specific to tuberculosis. Techniques to manipulate mycobacteria have also improved extensively; the conditional expression-specialized transduction essentiality test (CESTET) is currently used to determine the essentiality of individual genes. Finally, various biosynthetic assays using either purified proteins or synthetic cell wall acceptors have been developed to study enzyme function. This article focuses on the recent advances in determining the structural details and biosynthesis of arabinogalactan, lipoarabinomannan, and related glycoconjugates.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Cell Biology,Microbiology (medical),Genetics,General Immunology and Microbiology,Ecology,Physiology
Cited by
20 articles.
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