PRATIK SHAH

Use of bacterial metabolic pathways for designing new vaccines and drugs: American Society of Microbiology podcast

Use of bacterial metabolic pathways for designing new vaccines and drugs: American Society of Microbiology podcast

Announcer:

MicrobeWorld presents Meet The Scientist with Dr. Mary Buckley, a podcast that explores the life and work of researchers who sweat the small stuff, microbes, viruses, synthetic biology, nanotech, genomics and more. On this episode Mary talks with Pratik about why polyamines may hold the key for new ways to combat pathogens, his plans for the future and about advice he would give to young people considering grad school.

Mary Buckley:

You’re listening to Meet The Scientist. I’m Mary Buckley and I’m at the American Society for Microbiology’s General Meeting in Philadelphia. Where I’m interviewing some of this year’s recipients of ASM’s Scientific Achievement Awards. People who are making things happen in research, medicine and education today.

Right now I’m talking with Pratik Shah. He’s a graduate student in the Department of Microbiology and is a 2009 recipient of the Raymond W. Sarber Award granted to recognize students for research excellence and potential. Mr. Shah, welcome to Meet The scientist and congratulations on winning the award.

Pratik Shah:

Hey Mary, thank you for having me over. It’s my pleasure.

Mary Buckley:

Good. Your research focuses on polyamines and polyamine biosynthesis and transport systems in Streptococcus pneumoniae. Can you tell me a little bit about what polyamines are and why they’re important?

Pratik Shah:

Sure. So polyamines are these organic polycationic molecules and they have a hydrocarbon backbone. On these hydrocarbon backbones they have multiple amino groups and because of these amino groups, these molecules are positively charged. And all pro and eukaryotic cells naturally have polyamines inside them.

Mary Buckley:

Okay.

Pratik Shah:

For ages people have investigated the roles of polyamines in bacterial transcription and translation, and those fields are well studied and well defined. So most cells require polyamines for transcription and translation. Over the last few years, the focus has changed and in virulent bacteria, which causes diseases in humans. Polyamines now seem to regulate virulence phenotype and pathogenesis of bacteria.

And the second part of desecration is what my laboratory and I look into, the contribution of polyamines to virulence.

Mary Buckley:

Okay.

Pratik Shah:

So they’re required by all cells and usually they are involved in transcription and translation. And under certain conditions they regulate virulence as well.

Mary Buckley:

Okay. And your particular focus is on Streptococcus pneumoniae?

Pratik Shah:

Yes, that’s were my dissertation research focus is on.

Mary Buckley:

And what does that pathogen do?

Pratik Shah:

Streptococcus pneumoniae is an obligate human pathogen. And most humans carry it asymptomatically in the nasopharyngeal upper respiratory tract. Most people get the pathogen and we clear it off. But in some people who are immuno-compromised and other underlying conditions the bacteria don’t get cleared and cause bacteremia, meningitis and all sorts of invasive diseases, and pneumonia.

Mary Buckley:

Right.

Pratik Shah:

So it’s one of the leading causes of vaccine preventable deaths in the world right now. And significant mortality and morbidity is attributed to the pathogen.

Mary Buckley:

Right. Now do you envision any applications to come out of your work with polyamines and Streptococcus? Or a future work that follows up on the same concepts?

Pratik Shah:

Sure. I think I’m quite excited. So my dissertation research I investigated the roles polyamines in two ways. By therapeutic interventions and by prophylactic interventions.

And the therapeutic inventions I made mutants in polyamine biosynthesis and transport genes and Streptococcus pneumoniae. And when you make these mutants the bacteria, which cannot make polyamines or transport polyamines from the environment are severely attenuated in murine models of pneumococcal disease. And if you screen hard enough and long enough and if you look at certain parts of the genes of proteins, which are only present in pneumococcus, but absent in the mammalian host. We can design prophylactics, therapeutics and antibiotics, which target specifically the polyamines biosynthesis and transport genes.

And in another part of my thesis I looked prophylactic interventions. In that I used a surface molecule called polyamine transport protein D. And it’s a ABC transport molecule, which takes polyamines from the environment into the cell.

Mary Buckley:

Okay.

Pratik Shah:

And when I immunize mice with it as a vaccine antigen,the mice, which guard the protein. Will protect it against pneumococcal disease.

Mary Buckley:

Okay. So it’s like a component on the outer surface of the Streptococcus.

Pratik Shah:

Yes.

Mary Buckley:

And when you expose the mouse to it, it’s essentially immunized.

Pratik Shah:

Yes. So it seems to be immunogenic protein. So you can see how versatile it could get. Like some surface proteins and polyamine biosynthesis and transport can act as vaccine antigens. And if you make little genetic deletions in the pathways of polyamine biosynthesis and transport the pneumococcus is attenuated.

Mary Buckley:

Right. And you think maybe if you inoculated someone with the attenuated form, you’re thinking about-

Pratik Shah:

Yeah, sure.

Mary Buckley:

… Maybe it would out compete the more virulent Streptococcus?

Pratik Shah:

Yep so I’ve done some competitive index experiments. Where I’ve mixed the wild type and the mutant cells together in a mouse model. And every time the wild type is more fit in vivo than the mutant.

So it could also lead to live attenuated strain but of course more robust characterization is required before we move to humans or something like that.

Mary Buckley:

Now I understand that you moved from Mumbai to the United States to work on your PhD?

Pratik Shah:

Yes.

Mary Buckley:

How long ago was that?

Pratik Shah:

2004.

Mary Buckley:

So I’m gonna ask you the question that everyone loves to ask and no one likes to answer. When are graduating? And what are your plans after you graduate?

Pratik Shah:

Sure. So I think I’m fairly close to finishing up and I hate to put a timeline on it, but I think I’m fairly close.

Mary Buckley:

I don’t recommend putting a timeline on it, from my own experience!

Pratik Shah:

Thank you, you understand. So I’m fairly close and I want to do a postdoc in an academic setting.

So in my postdoctoral training I’m quite interested in understanding the roles of metabolic pathways in bacterial virulence in pathogenicity. And I personally think that for ages metabolic requirements of pathogens have always been downplayed in relation to virulence genes and virulence pathways of bacteria.

So for my postdoctoral training I would like to look at the contribution of metabolism to bacterial pathogens. And because I think that human pathogens who have lots of metabolic genes, use these metabolic genes for basically in vivo virulence. ‘Cause that’s what allows them to live.

Mary Buckley:

Right.

Pratik Shah:

In a human host.

And in addition to those metabolic genes, human pathogens also have genes, which cause diseases in human hosts. And I personally think those are pathogenicity factors. So I’m interested in teasing out the role of metabolism, virulence and pathogenicity in bacterial pathogens.

Mary Buckley:

Okay. So research is your calling or do you think you’d like to go into medicine or some other field?

Pratik Shah:

I think I’m quite happy at the bench. And I’m quite happy in the academic setting. I don’t think I would like to go to medical school at this point at least. I would like to continue doing research and understanding bacterial pathogenesis.

Mary Buckley:

Great. So you’ll do a postdoc for a few years and then you’ll be on the market for a faculty position?

Pratik Shah:

Absolutely. And I will be on the postdoc market too.

Mary Buckley:

Just give a heads up out there to all those microbiology and medicine departments who are looking for bright young faculty.

Do you have any advice for other young people who are interested in doing graduate work in microbiology?

Pratik Shah:

Well I don’t know if I have advice, I have a suggestion that I personally find it intellectually stimulating. And I think if you do in your graduate career … If you sit down with your mentor and come up with a project, which you really like and he’s willing to let you go do it. I think that really helps. There’s nothing like a project, which makes you get up in the morning and go to work. And I’ve been fortunate to get such a project thanks to my mentor.

Mary Buckley:

Great.

Well Mr. Shah thanks for talking with me today.

Pratik Shah:

Sure.