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 N-acetylmuramic 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!

Target for design of new drugs Vaccine development 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