Antimycobacterial Drugs –
Used for Treatment of
Biochemistry & Molecularbiology
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
• 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
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
• 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.
Mycobacterial (acid-fast) cell wall
• Thick, waxy and complex
• Higher fluidity in more external
regions than internal regions
• Contain porins (selective cationic
• Peptidoglycan - contains Nglycolylmuramic acid instead of
• Mycolic Acids (60% of cellular
• Lipoarabinomannan (LAM)
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
• 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)