Changing Views on the Nature of the Bacterial Cell: from Biochemistry to Cytology

When the authors were graduate students in the 1960s, the bacterial cell was generally viewed as an amorphous vessel housing a homogeneous solution of proteins. Trained as biochemists, we would break cells open, subject the disrupted cells to centrifugation, and separate the supernatant fluid from the membranous material that collected at the bottom of the centrifuge tube. Some enzymes, such as the replicase for the RNA phage F2, the subject of thesis research by L.S., were to be found in the supernatant fluid. Other enzymes, such as those involved in the biosynthesis of the O-antigen component of the lipopolysaccharide of Salmonella, the subject of doctoral work by R.L., were associated with the membrane. No differentiation was imagined other than the distinction between membrane proteins and cytoplasmic proteins. This is a view that persisted for a surprisingly long time. Of course, some bacteria have conspicuous proteinaceous appendages, such as flagella and pili, and some bacteria, such as Caulobacter crescentus, are conspicuously asymmetric. But only in this decade, and chiefly over the last few years, has it become apparent that cytoplasmic and membrane proteins can, and often do, have particular subcellular addresses, that these addresses can change over time, sometimes with extraordinary rapidity, and that an understanding of function requires knowledge not only of what a protein does but often of where it is in the cell.