Structure, function and biosynthesis of the Mycobacterium tuberculosis cell wall: arabinogalactan and lipoarabinomannan assembly with a view to discovering new drug targets.

نویسندگان

  • L J Alderwick
  • H L Birch
  • A K Mishra
  • L Eggeling
  • G S Besra
چکیده

In spite of effective antibiotics to treat TB (tuberculosis) since the early 1960s, we enter the new millennium with TB, currently the leading cause of death from a single infectious agent, killing more than three million people worldwide each year. Thus an understanding of drug-resistance mechanisms, the immunobiology of cell wall components to elucidate host-pathogen interactions and the discovery of new drug targets are now required for the treatment of TB. Above the plasma membrane is a classical chemotype IV PG (peptidoglycan) to which is attached the macromolecular structure, mycolyl-arabinogalactan, via a unique diglycosylphosphoryl bridge. This review will discuss the assembly of the mAGP (mycolyl-arabinogalactan-peptidoglycan), its associated glycolipids and the site of action of EMB (ethambutol), bringing forward a new era in TB research and focus on new drugs to combat multidrug resistant TB.

برای دانلود رایگان متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Lipoarabinomannan and related glycoconjugates: structure, biogenesis and role in Mycobacterium tuberculosis physiology and host–pathogen interaction

Approximately one third of the world's population is infected with Mycobacterium tuberculosis, the causative agent of tuberculosis. This bacterium has an unusual lipid-rich cell wall containing a vast repertoire of antigens, providing a hydrophobic impermeable barrier against chemical drugs, thus representing an attractive target for vaccine and drug development. Apart from the mycolyl-arabinog...

متن کامل

A truncated lipoglycan from mycobacteria with altered immunological properties.

Maintenance of cell-wall integrity in Mycobacterium tuberculosis is essential and is the target of several antitubercular drugs. For example, ethambutol targets arabinogalactan and lipoarabinomannan (LAM) biosynthesis through the inhibition of several arabinofuranosyltransferases. Apart from their role in cell-wall integrity, mycobacterial LAMs also exhibit important immunomodulatory activities...

متن کامل

The C-Terminal Domain of the Arabinosyltransferase Mycobacterium tuberculosis EmbC Is a Lectin-Like Carbohydrate Binding Module

The D-arabinan-containing polymers arabinogalactan (AG) and lipoarabinomannan (LAM) are essential components of the unique cell envelope of the pathogen Mycobacterium tuberculosis. Biosynthesis of AG and LAM involves a series of membrane-embedded arabinofuranosyl (Araf) transferases whose structures are largely uncharacterised, despite the fact that several of them are pharmacological targets o...

متن کامل

Issues in Mycobacterium tuberculosis Complex (MTBC) Drug Susceptibility Testing: Ethambutol (EMB)

1 Issues in MTBC Drug Susceptibility Testing: Ethambutol BACKGROUND Ethambutol (EMB) is an antituberculosis drug used as part of the first line treatment against Mycobacterium tuberculosis complex (MTBC).1 A primary role of EMB when used in initial combination antituberculosis therapy is to minimize the risk of drug resistance development to companion first line drugs, particularly isoniazid.2 ...

متن کامل

Biosynthesis of mycobacterial arabinogalactan: identification of a novel α(1→3) arabinofuranosyltransferase

The cell wall mycolyl-arabinogalactan-peptidoglycan complex is essential in mycobacterial species, such as Mycobacterium tuberculosis and is the target of several antitubercular drugs. For instance, ethambutol targets arabinogalactan biosynthesis through inhibition of the arabinofuranosyltransferases Mt-EmbA and Mt-EmbB. A bioinformatics approach identified putative integral membrane proteins, ...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

عنوان ژورنال:
  • Biochemical Society transactions

دوره 35 Pt 5  شماره 

صفحات  -

تاریخ انتشار 2007