Antimicrobial Chemotherapy

Mycobacteria are unusual bacteria. The cell wall structure is notable because it is very waxy. This makes it difficult to stain mycobacteria using conventional protocols. It also makes penetration of many antimicrobial drugs difficult. Furthermore, mycobacteria are very slow growing. Consequently, antimycobacterial therapy is very protracted. Unlike many pathogens, resistance to antimicrobials in mycobacteria typically results from point mutations in the bacterial chromosome, resulting in changes to the antibiotic target that render it no longer susceptible to the drug in question. This is why combinations of drugs are used to treat mycobacterial infections such as leprosy and tuberculosis. Antimycobacterial drugs are frequently associated with unpleasant side effects. This makes patient compliance in therapy difficult. To help overcome that problem, which undoubtedly contributes to the emergence of resistant strains, many health authorities are recommending Daily Observed Therapy: DOTs for short.

First discovered by Albert Schatz, working in Selman Waksman's laboratory, streptomycin was the first drug used successfully to treat tuberculosis. This is a protein synthesis inhibitor.

Chemical structure of streptomycin

Rifampicin is also used as an antimycobacterial: it acts by interfering with the DNA-dependent RNA polymerase of bacterial cells. The action of rifampicin prevents production of messenger RNA and thus ultimately stops protein synthesis.

Chemical structure of rifampicin

The antimycobacterial drug isoniazid inhibits the formation of very long chain fatty acids such as those found in the cell walls of mycobacteria. Isoniazid is used in the treatment of tuberculosis and other mycobacterial infections.

Chemical structure of isoniazid

Ethambutol is a first-line antimycobacterial drug that inhibits cell wall synthesis although its mode of action remains to be elucidated fully.

Chemical structure of ethambutol

Pyrazinamide is another first-line antimycobacterial drug that inhibits mycobacterial metabolism. Again, its mode of action remains to be elucidated fully.

Chemical structure of pyrazinamide