Comparison of the intrabacterial Na+,K(+)-ratio and multiplication in the mouse foot pad as measures of the proportion of viable Myobacterium lepraemurium.
Drug are generally screened for activity against Mycobacterium leprae by administration to M. leprae-infected mice, and the efficacy of a chemotherapeutic regimen is assessed by inoculating mice with M. leprae recovered from the skin-biopsy specimens obtained at intervals during treatment. Both methods are expensive and time consuming. Although a number of methods has been proposed for the rapid distinction between viable and non viable M. leprae, none has found wide acceptance. Earlier work had shown that the ratios of the intrabacterial concentrations of Na(+) and K(+) (Na(+),K(+)-ratio) of individual bacterial cells, measured by means of laser microprobe mass analysis, are a sensitive indicator of the viability of cultivable organisms. Assuming that the maximal value (the "limiting value") of the Na(+),K(+)-ratio of viable cultivable organisms is valid for non-cultivable species, the degree of correspondence between intrabacterial Na(+),K(+)-ratios of M. lepraemurium after treatment in vivo with isoniazid, streptomycin and clofazimine, and the ability of these organisms to multiply in mice were examined. A linear relationship between the proportion of viable organisms, calculated from the limiting value of the Na(+),K(+)-ratio, and that calculated from ID50 was found, suggesting that, at least for M. lepraemurium, the intrabacterial Na(+),K(+)-ratio predicts the effect of drugs measured by the much more demanding technique of mouse inoculation.
Haas
M
M
Division of Biophysics, Forschungsinstitut Borstel, Borstel, Germany.
Lindner
B
B
Seydel
U
U
Levy
L
L