When PPLO Became Mycoplasma
The smallest cell has had a long career in the spotlight
PPLO in the Mainstream
Twenty-five years passed before any other organisms of this type were discovered. Then in 1923, J. Bridre and A. Donatien reported on an organism similar to the causative agent of pleuropneumonia in cattle appearing as the causative agent of agalactia (faulty secretion of milk) in sheep. By the early 1930s a number of similar organisms were found, largely linked to animal diseases, and they were conveniently referred to as pleuropneumonia-like organisms following the first member of the group so discovered. Work on the group picked up in many countries, largely pursued by veterinary pathologists. In 1937, the first human disease, a pneumonia, was shown to be caused by a PPLO. And so PPLO moved into mainstream bacteriology, led by investigators such as Klieneberger-Nobel at the Lister Institute of Preventive Medicine in London. At that time a complication arose, which in retrospect was due to PPLOs being organisms that lacked a cell wall. Normal bacteria, which possessed a cell wall, could enter a phase where they lost their cell walls but were stable if the osmotic pressure of the medium was high enough. Cells in this stage were designated L forms and were generally capable of reverting to the walled condition. Because PPLOs lacked cell walls, there was 30 years of confusion as to the relation of PPLO to bacterial L forms.
When we undertook to study PPLOs it was not clear that they were normal cells surrounded by the usual cell membrane. They lacked cell walls, were so small they could barely be visualized with optical microscopy, and they had a tendency to clump in many strange ways. Cellularity and mode of replication was uncertain. The growth media used were complex, requiring a mishmosh of components such as blood serum to induce these balky creatures to grow. Drying and embedding specimens for examination by electron microscopy caused so much distortion that one could hardly rule between reality and artifact. All of this added to the problem of determining the size of the genome. On the plus side, a number of graduate students at the University of Connecticut and Yale joined the game, so there was a lot of help in tackling the problems.