concise structure of Mycobacterium tuberculosis in relation to anti-tb drugs

1. COLLEGE OF MEDICAL SCIENCES
GOMBE STATE UNIVERSITY
DEPARTMENT OF PHARMACOLOGY
STRUCTURE OF MYCOBACTERIUM
BY
• UG13/MDMD/1003
• UG13/MDMD/1005
MODERATOR: Pharm Sadiq M

2. CONTENTS
• INTRODUCTION
• STRUCTURAL COMPONENT
– Peptidoglycan
– Arabinogalactan
– Mycolic acid
– Lipoarabinomannan
– Phthioceroldimycocerates (PDIM)
– Sulfolipids
– Cord factor
• CONCLUSION

3. INTRODUCTION
• Mycobacterium tuberculosis is one of the most successful
pathogen of the present times. It operate via a complex
and indispensable cell wall that is responsible for the
persistence and resistance of the bacteria inside the human
host.
• The cell wall is responsible for many of the characteristics
of mycobacteria, which include
– Acid fastness
– Slow growth
– Resistant to detergent
– Antibiotic resistance
– Antigenicity
– clumping

4. STRUCTURAL COMPONENTS
Mycobacterial cell wall can be divided into two parts:
– Soluble parts
– Insoluble fraction
SOLUBLE PARTS
• The lipid which are solubilized easily are the free lipids
that are present in the outer part of the cell wall
• and those which remain intact form the inner part of
the cell wall.
Insoluble fraction
• The insoluble fraction form backbone of the cell wall
and is made up of Peptidoglycan, arabinoglycan and
mycolic acid

6. PEPTIDOGLYCAN
• The peptidoglycan of Mycobacterium contains
alternate repeating units of N-acetyl
glucosamine, N-acetyl muramic acid (glycated)
and N-glycolylmuramic acid linked via peptide
bridges.
• The cross linking peptide that links the dimer
of NAG and NAM helps in its survival against
conventional proteases
• Inhibited by D-cycloserine and B-lactams

8. ARABINOGALACTAN
• This is sandwiched between peptidoglycan on
one side ad mycolic acid on the other and
hence form PAM(peptidoglycan-
arabinogalactan-mycolic acid) complex . The
arabinogalactan is made up of arabinan and
galactan components attached via a linker

9. MYCOLIC ACID
Definition :A homologous series of c60-c90 long
chain alpha-alkyl-beta-hydroxy fatty acids, represent
essential components of the Mycobacterial cell wall.
FUNCTION OF MYCOLIC ACID
• Growth and Survival
• primary determinant of permeability due to their
hydrophobic nature forming like a shell around the
organism
• They defend mycobacteria from attack of cationic
proteins, lysozyme and oxygen radical as well as
protect from complement deposition in serum
• allow the bacterium to grow inside macrophage,
effectively hiding it from host immune system.

10. MYCOLIC ACID con’t
• They are found as esters of an
arabinogalactan as well as free lipids in form
of trehalose di mycolate(TDM)..
• Both Arabinogalactan-mycolate and trehalose di
mycolate(TDM) provide a protective thick cell wall
and protect the tubercle bacillus from antibiotic and
host’s immune system
• Its inhibited by Isoniazid and Ethionamide

11. MYCOLIC ACID PATHWAY AS TB DRUG TARGET

12. SOLUBLE LIPIDS
• The soluble parts comprises of
Lipoarabinomannan,
Phthioceroldimycocerates (PDIM), sulfolipids,
cord factor etc.

13. LIPOARABINOMANNAN (LAM)
• Is a polysaccharides containing Araf and mannopyranosyl
residues
• It lacks mycolic acid elaboration
• It serve as modulin with immunoregulatory and anti-
inflammatory effects,
• Its primary function is to inhibition of T cell proliferation
and of macrophage macrobicidal activity via diminished
IFN-γ response and scavenge oxidative radicals which allow
for dissemination of the mycobacterium
• Mannosylated LAM inhibit production of TNF-α and IL 12 by
macrophage and modulate its apoptosis via binding to host
macrophage mannose receptors.
• Its inhibited by Ethambutol

15. Phthioceroldimycocerates (PDIM),
• PDIM, phthiocerol and
phenolphthioceroldimycocerosateses are a
group of free lipids in the upper layer of the
cell wall of mycobacterium that serve as a
virulent factor and is required for the
maintenance of cell wall permeability and its
specific to the pathogenic mycobacteria

16. SULFOLIPIDS
• They play an important role in the virulence of
M. tuberculosis primarily at early stage of
infection.
• They also inhibit oxidative phosphorylation as
well as inhibit the fusion of lysosome with
phagosome thereby modulating the immune
response of the human host.

17. CORD FACTOR
• Also called trehalose 6,6-dimycolate is a surface
glycolipids found in higher concentration than the
other 2.
• It is an inhibitor of PMN (polymorphonuclear
neutrophils) migration
• It play an important role in granuloma formation
inside the host.
• It also inhibits fusion of phagosome with
lysosome and thereby prevents acidification of
the phagosome

18. CONCLUSION

19. REFERENCE
• “An Insight Into The Cell Wall Of
Mycobacterium Tuberculosis” International
Journal of Science and Research, ISSN (online)
2319-7064. index copernicus value (2013):
6.14