THE RESPIRATORY METABOLISM OF MURINE LEPROSY BACILLI

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Abstract
Murine and human leprosy bacilli are obligate parasites which have not been cultivated in vitro. Information which bears on the cultivation problem has been obtained by studying the metabolism of Mycobacterium leprae-murium separated from infected rat testicles by differential centrifugation. The bacilli show an endogenous respiration with an optimum at pH 7.5. Like tubercle bacilli, their respiratory capacity is damaged by anaerobic storage. Fresh suspensions fail to oxidize any one of 50 test substrates including intermediates of glycolysis, members of the Krebs cycle, amino acids, fatty acids, and complex substances frequently used in culture media such as peptone and digests of casein. Certain complex materials, notably rat serum, are toxic. Yeast and liver extracts stimulate respiration as do also proteins with a strong binding capacity such as bovine serum albumin and protamine. It is thought that yeast and liver may function in part by supplying factors removed from the bacilli during the purification process, while the proteins act by removing inhibitors and/or replacing the function of structural proteins lost from the bacilli. The highest respiration rates were observed in the presence of combined albumin and yeast supplement. Even in the presence of this mixture with added vitamins and co-factors, respiration is not further increased by the addition of substrate. The failure of murine leprosy bacilli to oxidize substrates and make a net gain in energy, coupled with the unexpected toxicity of certain complex substrates probably explains the failure of in vitro cultivation. It is suggested that the definition and soln. of the metabolic difficulties which concern these bacilli offers more hope for the soln. of the cultivation problem than does the practice of inoculating various empirically compounded media.