Antitubercular Drugs


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Antitubercular Drugs

  1. 1. Antimycobacterial Drugs – Used for Treatment of Tuberculosis By, Ishaque P.K Biochemistry & Molecularbiology Pondicherry University
  2. 2. Introduction to Mycobacteria • Aerobic bacilli • Gram positive – Do not stain well with Gram stain • Acid fast – Bind phenol based dyes (carbol fuchsin) and resist acid alcohol decoloration (Ziehl-Neelsen stain). • Non spore forming • Non motile, rods with varying sizes (1-10μm) • Catalase positive • Many mycobacteria produce pigments on culture • Relatively simple growth medium required • Rapid (<7 days) or slow growing (weeks or months) • Most of them are pathogens, they are slow growing
  3. 3. Mycobacterium species of clinical importance • Mycobacterium tuberculosis : TB in humans but also cats, dogs, pigs, chickens, parrots, canaries, guinea pigs and mice • Mycobacterium bovis : bovine tuberculosis, also TB in man, other ruminants, pigs and more rarely in horses, dogs, cats. • Mycobacterium avium subsps.Paratuberculosis : Johne’s disease in cattle, sheep, goats and deer . • Mycobacterium avium complex : TB in birds, poultry very susceptible. Pigs susceptible but not cattle. Sporadic cases in horses, dogs and cats. Opportunist in man (AIDS – M. avium intracellulare) • M. Leprae - Leprosy (man, mice, armadillos) • M. lepraemurium, M. ulcerans, M. kansasii, M. fortuitum and M. Chelonae Skin ulceration and lymph node involvement in many different species, Chronic RTI
  4. 4. Virulence factors of Mycobacteria • Cell wall components • Mycolic acids – resist phagocytic digestion. • Sulfatides – prevent phagocyte activation and phagosomelysosome fusion. • Trehalose di-mycolate (cord factor) – Inhibits phagocyte chemotaxis, activation, phagosome-lysosome fusions and digesion. • Lipoarabinomannan (LAM) – prevents phagocyte activation and digestion within the phagocyte. • Mycosides – prevent intracellular killing and digestion • Cell wall antigens in general induce DTH • Other factors include SOD (superoxide dismutase) and heat shock proteins.
  5. 5. Mycobacterial (acid-fast) cell wall General Features • Thick, waxy and complex • Higher fluidity in more external regions than internal regions • Relatively impermeable to hydrophilic solutes • Contain porins (selective cationic channels) Main Components • Peptidoglycan - contains Nglycolylmuramic acid instead of N-acetylmuramic acid • Arabinogalactan • Mycolic Acids (60% of cellular envelope) • Lipoarabinomannan (LAM)
  6. 6. Diagnosis of Mycobacterial infection • Immunological detection • ‘tuberculin’ testing- using PPD (purified protein derivative) from the relevant bacterial species. • Gama interferon assay • Laboratory Diagnosis - Microscopy (e.g. Ziehl Neelsen staining, rhodamine/auramine fluorescent stain) of appropriate specimens from site of infection • Culture – of lymph node, tissue lesions, sputum, aspirates, milk • Decontamination of specimens with sodium hydrochloride, sodium triphosphate, oxalic acid • Lowenstein Jensen medium (slants) incubated for up to 8 weeks • Genomic detection (e.g. PCR)
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