Transcript The Acid Fast Cell Wall - University of the Witwatersrand

The Acid Fast Cell Wall
Dr. Jennifer Coetzee
Definition
• Cell wall that retains carbol fuchsin dye in
the presence of acid alcohol
• Stains use in lab to detect acid fastness:
– Ziehl-Neelsen
– Kinyoun
Organisms with Acid Fast Cell
Wall
• Mycobacteria
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Mycobacterium tuberculosis
Mycobacterium leprae
Mycobacterium bovis
57 other mycobacterial species!
• Nocardia species
– Nocardia asteroides
– And many more
Structure of an Acid Fast Cell
Wall
• 3 major molecules:
– Peptidoglycans
• Contains N-glycolylmuramic acid instead of Nacetylmuramic acid found in other bacteria
• Prevents osmotic lysis
– Arabinogalactans
• 2 lipopolysaccharides, lipoarabinomannan (LAM)
and lipomannan
– Mycolic acids
Mycolic Acids
• Almost exclusive to mycobacteria
• Essential to acid fast staining properties
• Up to 60% of composition of mycobacterial
cell wall
• Branched fatty acids with a short and long
branch (22-24 and 40-64 carbons)
• MTB genome 4000 genes
• Mostly coding for enzymes involved in
lipolysis and lipogenesis
Lipoarabinomannan
• Directs macrophage function
• Inhibits the processing of mycobacterial
peptides/proteins by antigen presenting cells
• Induces tumor necrosis factor (TNF-ά)
• Considered a mycobacterial virulence factor
Permeability of Cell Wall
• Membrane proteins called porins control
diffusion of hydropilic molecules
– Relatively impermeable to hydrophilic solutes
• Permeability of lipophilic molecules:
– Inner leaflet low fluidity, nearly crystalline
structure
– Diffusion through lipid bilayer requires fluid
interior
– Bilayer uncommonly thick
Clinical Implications
• High degree of intrinsic resistance to most
antibiotics
– Low permeability
– Unusual structure
• Slow growth rate
– Clinicians awaiting culture results!
• Relatively resistant to drying, alkali, and
many more chemical disinfectants
– Very difficult to prevent transmission of M.
tuberculosis in institutions
– Infection control implications
• Target for design of new drugs
• Vaccine development
• Better understanding of pathogenesis,
immunity
Summary
• Cell wall structure totally different from
other bacteria
• Mycolic acids major component,
responsible for acid fast staining
characteristic
• Also peptidoglycan, arabinogalactans
• Clinical implications of the above
References
• Rodrigo Gay Ducati et al. The resumption
of consumption. Mem Inst Oswaldo Cruz,
101(7), 2006
• Brennan PJ, Nikaido H. The envelope of
mycobacteria. Annu Rev Biochem.
1995;64:29-63
• Barry CE, Mdluli K. Drug sensitivity and
environmental adaptation of mycobacterial
cell wall components. Trends Microbiol.
1996;4(7):275-81