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You work a lot with virulence genes and antivirulence genes. A virulence gene confers improved pathogenicity, it basically makes the bacterium better at making us sick, but what is an antivirulence gene?
In a nutshell, an antivirulence gene is a gene which was part of the core genome of the organism as it evolved from the nonpathogen (perhaps commensal or environmental organism) and because of selective pressures it was eliminated.

 

You discovered and named the phenomena of "black holes" in bacterial genetics - can you describe what black holes are and why are they important?
The first evidence we had of an antivirulence gene was a gene called cadA - a gene that encodes lysine decarboxylase. Shigella evolved from E. coli (we have very good evidence for this), so if you line up the genomes of Shigella and E. coli, for the most part they're very very similar: the genes are in the right places in both strains. The cadA gene is present in greater than 90% of E. coli, but is uniformly absent in Shigella. In fact, when the genome sequences of these organisms came out a few years ago, it turns out that all the ShigellacadA or mutations in the cadA gene. When we first studied this region of the chromosome, we found that not only was cadA deleted from S. flexneri, but there was a huge hole in the genome of Shigella relative to E. coli k12. So those are black holes.

 

A pathogen is a pathogen because of its virulence genes, and your work shows that these genes are dynamic - changing and deleting to suit an organism's needs. Given this kind of mutability, do you think the species concept is appropriate when it comes to pathogens? Is a Shigella really always a Shigella?
After many years of study, we know that one could accurately call S. flexneri a subspecies of E. coli. Taxonomically, that would be correct, but practically, it would be confusing. We teach medical students and we adhere to the general conventions of defining pathogens the way they've been defined the last 120 years or so because that's the way that people understand the pathogen. I'm happy with the nomenclature we have now for Shigella.

 

You've been at the Uniformed Services University of the Health Sciences in Bethesda, Maryland since 1986, but I think this institution is unfamiliar to a lot of people. Tell us what the Uniformed Services University of the Health Sciences is?
The Uniformed Services University is the federal health university for the U.S.. It is a medical school and a graduate school of nursing and a graduate school that gives Ph.D.s and masters' degrees in a number of the health sciences. It was established in 1976 by an act of congress to create a school of medicine that would train physicians for the uniformed services - the Army, Navy, Air Force, and the Public Health Services.

 

What's next for your lab?
One of the big efforts that we've made over the past few years is to try to develop some genetic tools for studying Chlamydia, and there are several major challenges to doing this. We've been working on creating genetic tools for the last dozen years and it's only been within the last eight to 12 months that we've made some breakthroughs. We hope to get published within the next couple months.

 

What do you think is the most understudied microbial system? 
Obligate intracellular bacteria are the most understudied. If you look at the literature, organisms like Chlamydia, Rickettsia, Coxiella, Mycobacterium leprae, we don't know a whole lot about them because they're so hard to work with.

 

What is your favorite microbe?
I would say that I love yeast because they're responsible for giving us bread and beer.

 

If you could name a new microbe right now, would you name it after yourself?  If not, how would you name it?
I don't think I would name it after myself. It's tough to come up with a really good name that doesn't sound like something from "Harry Potter".

 

What advice would you give students about life as a microbiologist working in a medical school?
Working in a medical school has a lot of advantages because it allows you to come into contact with the people who work with pathogens as they effect people - clinicians. You can really keep your feet grounded in your organism as a pathogen and not just as an interesting system to study.

 

What is something about you that most people don't know?
I speak French. I did my postdoc in Paris at the Institut Pasteur and it was there that I met my wife, Bernadette. All of my kids are bilingual because they're been brought up in a bilingual household.


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