Today while up in the attic, I came across an old picture. It is a scanning electron micrograph of mutant Staphylococcus aureus bacteria showing cells that are shrunken and broken. What is Staphylococcus aureus? It was once called the “old man’s friend” because it ended the life of people on the brink of death and just needed a little help. It lives on the skin of all of us but becomes a pathogen only if we are weakened. Why do I have this picture? It is because I took it as part of my Ph.D. research, which confirmed the mode of action of penicillin. Tipper and Strominger had noted that certain nucleotides used in cell wall biosynthesis accumulate when S. aureus cells are treated with penicillin in theory because the enzymes that would convert them to cell wall are inhibited by penicillin causing the precursors to accumulate. My work showed that conditional temperature sensitive mutants of these enzymes would cause the same accumulation of cell wall nucleotides. This proved that it was inhibition of these specific enzymes that caused cell wall to not be built or repaired in the presence of penicillin. The trick was in figuring out how to select for such mutants. This find has brought back a lot of old memories. One Saturday the extract in a series of samples turned red and I knew I had my Ph.D.
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