The 2018 paper was published by researchers at the University of Texas, showing how T. pallidum could be grown in the laboratory5. It’s not perfect, it’s difficult, but it was a revolution. It has taken 100 years from discovering the bacterium to get to here.
To grow T. pallidum, it has to be in the presence of other mammalian cells – in this case, rabbit cells. Essentially, the mammalian cells are supporting the growth of T. pallidum. We don't know how, or how the cells interact, we know almost nothing about that - this is one of the questions we have. Setting up the culture is challenging. Because there are so many steps, there is a high risk of contamination.
Another difficulty is that T. pallidum is microaerophilic – oxygen is toxic to it, so you need a special lab set-up. It’s also time-consuming – it takes seven days for the bugs to replicate sufficiently to be able to divide them and grow more. And, because of their shape, you can’t see them under the light microscope, you need dark field microscopy, and this requires a little bit of training, as you need to know what you are searching for. The analysis is hard too, because you’ve got a mix of cells in there, and the mammalian cell genome is about 3,000 times larger than the bacterial one. Genetic material, metabolites, or proteins that the bacteria produce are all mixed up with the mammalian ones, and tiny.
The result – only a few labs in the world can do it, and we’re the only ones in the UK. But now, finally, being able to grow it opens up huge opportunities for us. Most of our observations are new – not been seen before. Really, I want to do everything! Every time I give a talk people ask about using more techniques that would answer our questions from different perspectives. I would love to! But the day has only 24 hours, and we have to focus on one thing at a time. Focusing on just one thing has been the biggest challenge for me so far.
“It’s a new challenge working within a microaerophilic chamber, as we’ve not worked in them before. We are working out the logistics, but it will enable us to run more experiments. Previously, we were limited to 30 minutes of working time outside of the incubator – anything after that and the bacteria become stressed.”
Technical Specialist in the Parasites and Microbes Programme, Wellcome Sanger Institute