First off, could you explain what Pneumocystis carinii is and what it does?
Pneumocystis carinii is a species in the genus Pneumocystis that now has five formally described members. Pneumocystis are fungal pathogens that we believe are commensals that are with us throughout our entire life. They really don't cause us any problems unless our immune systems become debilitated. They're ubiquitous, as far as we know, in the world, so all of us have antibodies to Pneumocystis.
How many people come down with Pneumocystis pneumonia every year and is it more prevalent in other parts of the world?
That's a difficult question to answer because it's not considered a reportable disease by the Centers for Disease Control and Prevention. In the U.S., before the age of effective treatment against HIV, there were tens of thousands of cases per year. Now there are thousands of cases. The hot spots are undeveloped countries, such as those found in Southeast Asia and also in sub-Saharan Africa, where HIV still persists in large numbers.
You head up the Pneumocystis genome project, and the organism used for sequencing was P. carinii, but the strain that infects humans is P. jirovecii. Why sequence P. carinii and does this cause any problems with interpreting your results?
Unfortunately, the major problem that's plagued Pneumocystis researchers is the lack of a long-term in vitro culture system. This has forced us to use animal models as a way of understanding the genus itself. So, we learn a lot about the genetic structure of the rat [Pneumocystis] model, and we're presently doing the mouse model as well, and there are enough similarities between these [Pneumocystis] species that allow us to make different types of predictions.
What are some of the more surprising results to come out of the genomics work?
I was surprised that Pneumocystis is able to have its own metabolism. As microbes coevolve with their hosts, they lose the ability to perform certain metabolic cycles, they lose certain genes because they take the nutrition from the host or they'll use the host ATP for their own. That really is the true sign of a parasite - where they're rather deleterious to the host. But Pneumocystis seems like a more compatible pathogen.
Scientists used to think that Pneumocystis was a protozoa, but we now know that it's a fungus. I see from your CV that the Society of Protozoologists honored you with their young investigator award back in the eighties. Any plans to send the prize back?
Oh no. We've reconciled this - we call all of these organisms "protists" so we can get away with that.
What's next for your lab?
If you treat Pneumocystis infected rats or mice with a new line of drugs called glucan synthase inhibitors, you can cause the infection to shift from one of both sexual and asexual production to mostly one where there are no cysts and there are only the trophic forms, which is the form that we believe asexually reproduce. We're going to use this drug as a molecular tool to dissect the lifecycle a bit more, because those animals with just the trophic forms cannot transmit the infection. It's our hypothesis that the cyst form is the transmissive propagule of Pneumocystis. We're going to follow up on those studies.
What do you think is the most understudied microbial system?
I'm very interested in the coral reefs. In terms of the fungal diversity of the coral reefs specifically. I'd like to see a census taken.
If you could name a new microbe right now, would you name it after yourself? If not, how would you name it?
I would name it either for the host in which it appears or as an homage to one of the early workers in Pneumocystis, because it's been a very difficult organism to work with, and people have to be quite patient and really persistent in trying to understand it.
What advice would you give students about life as a microbiologist working in academia and medicine?
It's a little trite, but try and think outside the box. And also, you have to love what you do to be able to stick to it, so make sure you're committed and you love the stuff.
What is something about you that most people don't know?
Now we're going to have the tie-in to the coral reefs. I'm a scuba diver. French Polynesia is my favorite dive spot. Very, very vibrant, and lots of mega-life, lots of very nice little tiny things that I like to look at - nudibranchs and things like that. There are some other places in the Caribbean that are not in very good shape.