Small but perfectly formed
As micro-organisms go, mollicutes are among both the simplest and the most sophisticated. Believed to have devolved from common ancestors of Clostridia and Lactobacilli around 2.5 billion years ago, there are more than 100 known species - and there may well be others that have not yet been discovered.
As micro-organisms go, mollicutes are among both the simplest and the most sophisticated. Believed to have devolved from common ancestors of Clostridia and Lactobacilli around 2.5 billion years ago, there are more than 100 known species - and there may well be others that have not yet been discovered.
They may have discarded up to half their genetic material - the smallest, M. genitalium has only 483 genes compared with E. coli's 4,000 - but it is their very simplicity that makes them difficult to detect and eradicate.
Alarmingly, it is estimated that around a third of all cell cultures could be infected, and the first clue to their presence is a drop in yield.
Because they are present throughout the environment, in plants and animals, tracking down the source is no easy task. And their ability to adapt to their host means that if they were to establish themselves in the processing environment itself and become part of the plant bioburden, eradicating them would be a major challenge.
But it is not just their potential pathogenicity nor the reduction in bioreactor yields that makes mollicutes so significant for biopharmaceutical manufacturers. Their very presence suggests that something is going wrong somewhere along the line where QA/QC is concerned or that care is lacking during the manufacturing process .
Now that media sterilisation is achieved by means of filtration rather than autoclaving, the option of destroying them through heat is no longer there. If the correct pressure and temperature parameters are not applied to the filter process, even a 1µm filter may allow mycoplasmas through. And the lack of any harmonised validation for filtration systems is doing nothing to remedy this.
But by far the greatest risk where mollicutes are concerned is ignorance. Their incidence is almost certainly underestimated and under-reported.
Awareness of the risk is the first step and admitting that there is a problem is the second. Mycoplasmas may be unseen, undetected and unidentified, but that does not mean they are not there.