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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 – – – – 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
