Download - Antitubercular Drugs
Antimycobacterial Drugs –Used for Treatment of
Tuberculosis
By,Ishaque P.KBiochemistry & MolecularbiologyPondicherry University
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
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
• Cell wall components
• Mycolic acids – resist phagocytic digestion.
• Sulfatides – prevent phagocyte activation and phagosome-lysosome 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.
Virulence factors of Mycobacteria
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
N-glycolylmuramic acid instead of N-acetylmuramic acid
• Arabinogalactan• Mycolic Acids (60% of
cellular envelope)• Lipoarabinomannan (LAM)
Mycobacterial (acid-fast) cell wall
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)