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Chapter 8 : Morphing Chemistry into Microbial Physiology
One expects bacterial growth to be slow based on chemical principles, but at a certain low temperature--the minimum temperature for growth—growth stops completely. The author's studies showed that many things go wrong simultaneously at the minimum temperature of growth, and metabolism therefore stops completely. By isolating and studying mutant strains with an increased minimum temperature of growth (called as cold-sensitive mutants), it was possible to determine what single change increased the minimum temperature of growth of one particular mutant strain. The author isolated cold-sensitive mutants of Escherichia coli that were unable to grow below 20°C (the minimum temperature for growth of wild type E. coli is 8°C). In these mutants, biosynthesis of histidine was cold sensitive. The mutations causing this type of cold sensitivity lay in hisG—the gene encoding the enzyme that catalyzes the first step of the pathway, the one sensitive to feedback inhibition by free histidine. The phenomenon of change in regulatory responses of proteins with temperature proved to be a general one; however, one cannot predict whether regulation becomes more or less severe as temperature is lowered. From the study of cold-sensitive mutants, the author concluded that bacteria stops growing at low temperature because weakening of hydrophobic bonds causes conformational changes in proteins that preclude growth largely by distorting regulation or stopping assembly processes.