Biology 216 - Lect 27 Mycobacterium General Order: General, atypicals, TB, leprosy I. Mycobacterium in general (fungal bacterium) Gm+ rods, stain poorly, non-motile, non-sporeforming, acid fast (mycolic acid - C90) Ubiquitous in soil, animals (except M. tuberculosis and M. leprae) Fungal-like: crusty, slow growing II. Atypical mycobacteria - MOTTs - Mycobacterium other than TB; (NTM) - Non-TB Mycobacterium Used to be considered saprophyte, however, now recognized cause of TB in comprom Confusing to learn each (read for own interest): M. marinum (fish tank granuloma) Know: M. avium-intracellulare complex (MAC) - difficult to speciate and treat. A. Classification Groups- based on Runyon scheme 1. Speed of growth - most take greater than 10 days. 2. Scotochromogenic - pigment in the dark 3. Photochromogenic - pigment after 1 hour light exposure. 4. Niacin accumulation - M. tuberculosis makes and stores; colorimetric assay. 5. Other biochemicals to speciate within the group: tween hydrolysis, sugars... B. Pathogenesis - same for all species (chronic disease). 1. Reservoir - MOTTS not person to person (water, soil,.....) 2. Transmission - inhalation, break in skin, ... 3. Compromised host (immunological or lung) and high numbers required. Middle age smokers, previous lung disease, AIDS, autoimmune (rheumatoid arthritis-Portland) 4. CMI is protective, humoral occurs, but insignificant. 5. Lesion - granuloma (tubercle) - Macs, giant cell, fibroblasts, fibrin, Ca++ Dynamic equilibrium - must rebuild to maintain wall. C. Isolation and ID - hood and special containment 1. MOTT - require repeat isolation, closed lesion, history of compromised, + x-ray 2. Butte Co - solubilize (N-acetyl-L-cys); decontaminate; pellet; Lowenstein-Jensen/7H11, set up tests to group, send to state to speciate. 3. DNA probe by state - 125I-DNA probe to rRNA for TB (very sensitive and specific) D. Treatment - long term combination antibiotics (INH, Sm, Rif, Ethambutol) Isoniazid (nitrogen/ring, simple) - block mycolic acid synthesis Ethambutol (similar structure to INH) - block CHO metabolism High rate resistance to these INDIVIDUALLY, so combination for long time (6 - 12 months) MDR - evolved from not taking all pills - Nausea discourages completion of drugs. - Outpatient treatment - 10 % compliance when many pills - Food and clothing vouchers to encourage Now combinations available in one pill 50 % fatality with MDR Mycobacteria (surgical removal as last resort) New fluoroquinolones effective, but resistance is developing. Must penetrate lesion and bacteria - extended therapy 1 - 2 years. Sensitivity testing (2 more weeks) MAC - No effective cure - 4 - 6 antibiotics