Mycobacterium leprae in Mice: Minimal Infectious Dose, Relationship Between Staining Quality and Infectivity, and Effect of Cortisone

Abstract

Shepard, Charles C. (Communicable Disease Center, U.S. Public Health Service, Atlanta, Ga.), and Dorothy H. McRae . Mycobacterium leprae in mice: minimal infectious dose, relationship between staining quality and infectivity, and effect of cortisone. J. Bacteriol. 89: 365–372. 1965.—The minimal infectious dose of Mycobacterium leprae in mouse foot pads was found to be on the order of 10 solidly staining bacilli. In a titration experiment, the actual number found was 3.4 to 34 solid bacilli, and the order of magnitude was confirmed by experience with inocula containing varying numbers of solidly staining leprosy bacilli from mouse passage and from clinical sources. The acid-fast staining quality of leprosy bacilli was related in a useful way to the subsequent rate at which bacillary growth appeared. When the proportion of solidly staining bacilli was high, the calculated generation time was shortest, and the lower the proportion, the longer the generation times. The results were in accord with the hypothesis that all viable bacilli are solid, and that when they die, most of them become nonsolid. Varying proportions of the dead bacilli, perhaps up to 10%, remain solid, at least temporarily. The growth curve of M. leprae in mice was followed in several experiments with total counts of acid-fast bacteria and determination of the ratio of solid bacilli. What had been called a maximal stationary phase was seen to consist of sequential phases of conversion of solid to nonsolid bacilli (death), reappearance of solid bacilli (growth), and conversion of solid to nonsolid bacilli (death). When cortisone was administered, leprosy bacilli grew somewhat more slowly during the logarithmic phase, but attained a higher level, especially of solidly staining bacilli.