Effect of mycostatin and fungizone on the growth of Histoplasma capsulatum in tissue culture.

Rous and Jones (1916) demonstrated that typhoid bacilli phagocytized by leucocytes were protected from the bactericidal activity of normal rabbit serum and of 0.O1N potassium cyanide. These workers were among the first to emphasize that "living phagocytes are able to protect ingested organisms from the action of destructive substances in the surrounding fluid. ... " Many years later, Mackaness (1952) reported that cells of Mycobacterium tuberculosis within macrophages were protected from bactericidal concentrations of several antibiotics. More recently it has been shown that penicillin, chloramphenicol, erythromycin, and novobiocin fail to kill phagocytized gonococci in tissue culture (Thayer et al., 1956/ 1957). Suter (1952) has shown, however, that intracellular tubercle bacilli are as susceptible to isonicotinic acid hydrazide as are those suspended in Tween-albumin medium. This latter observation suggests that at least some drugs will be found that are equally effective against intracellular and extracellular organisms. Murat et al. (1959) have proposed a technique involving tissue cultures to be used for screening antibiotics and other drugs for their activity against intracellular bacteria. The observation that intracellular organisms remain essentially unaffected by concentrations of many drugs which are bactericidal or bacteriostatic to extracellular forms has led to the development of an experimental technique whereby host-parasite relationships may be studied on a cellular level. The technique has many modifications, but consists essentially of allowing phagocytic cells (macrophages) in tissue culture to ingest microorganisms, stopping extracellular mul-