Utilization of Amino Acids During Growth of Mycobacterium tuberculosis in Rotary Cultures

Marked differences were observed in the response of actively growing cells of the saprophyte, Mycobacterium smegmatis 607, and the avirulent human strain, M. tuberculosis (H37Ra), to several different nitrogen sources in aerated (rotary) cultures. The growth-promoting effect and utilization of equimolar concentrations (5 mumoles/ml) of l-alanine, l-aspartic acid, monosodium glutamate, or ammonium chloride were compared with that of l-asparagine, the normal nitrogen source, in Sauton synthetic liquid medium. The saprophyte grew equally well with each nitrogen source. However, marked differences were seen with H37Ra. Based on the rate of growth and cell yield, the relative growth-promoting effect of the amino acids for H37Ra is: alanine >> glutamate > asparagine > aspartic. Utilization of alanine, glutamate, and aspartic correlated well with growth. In contrast, utilization of asparagine during early growth of H37Ra was severalfold greater than that of either alanine or glutamate. Extracellular amino acids accumulated during the metabolism of asparagine but not during the utilization of the other nitrogen sources. Balanced metabolism of asparagine does not take place during aerated growth of H37Ra in asparagine media. During the metabolism of l-asparagine by M. tuberculosis (H37Ra) in aerated liquid cultures, metabolic controls may be exerted which impede protein synthesis.