Amy L. Davidson talks with
ScienceWatch.com and answers a few questions about
this month's New Hot Paper in the field of Microbiology.
The author has also sent along images of their
Article Title: Structure, function, and evolution
of bacterial ATP-binding cassette systems
AL;Dassa, E;Orelle, C;Chen, J
Journal: MICROBIOL MOL BIOL REV, Volume: 72, Issue: 2,
Page: 317-364, Year: JUN 2008
* Purdue Univ, Dept Chem, 560 Oval Dr, W Lafayette, IN
* Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA.
* Inst Pasteur, CNRS, URA2172, Unite Membranes
Bacteriennes, F-75724 Paris 15, France.
* Purdue Univ, Dept Biol, W Lafayette, IN 47907 USA.
Why do you think your paper is highly cited?
Does it describe a new discovery, methodology, or synthesis of
Our team of authors put a lot of time and effort into compiling as complete
a review of ATP-binding cassette (ABC) transporters in bacteria as we
could, and combined that with an up-to-date discussion of progress in
understanding of the structure and mechanism of ABC transporters. It's
definitely a synthesis of knowledge.
Would you summarize the significance of your paper
in layman's terms?
accompanying slides and descriptions.
ABC transporters use the energy generated from ATP hydrolysis to transport
solutes across the membrane. In bacteria, these proteins are critical for
survival, since they function in the uptake of nutrient and in the
secretion of toxins and antimicrobial agents. In humans, several genetic
defects in these proteins are implicated in more than a dozen disease
states involving transport deficiencies including cystic fibrosis,
hyperinsulinemia, and macular degeneration.
Broad-based multidrug resistance, as seen in a variety of human cancers can
also be traced to ABC transporters that function as nonspecific efflux
pumps. Furthermore, the expression of ABC transporters at the blood-brain
barrier has been shown to limit the penetration of drugs and other agents
into the brain. By deciphering the mechanism of action of a diverse set of
ABC transporters, such as those present in bacteria, we may discover new
ways to inhibit microbial growth and improve the drug delivery process.
How did you become involved in this research, and
were there any problems along the way?
I started work on the maltose transport system as a postdoctoral fellow at
the University of California, Berkeley, with the goal of reconstituting
transport activity in vitro, in artificial membrane vesicles.
Reconstitution requires the functional overexpression of these membrane
proteins, which is often a challenge, but, once successful, it really opens
up the door to biochemical, biophysical, and structural analysis.
I was fortunate to be able to team up with two outstanding
crystallographers, Dr. Jue Chen, and
Dr. Florante Quiocho, who worked very hard for many
years to solve the structure of this transporter.
Where do you see your research leading in the
We hope to understand how different types of substrates are moved across
the membrane by ABC transporters now that we have an understanding of how
small nutrients are brought into the cell. Devising mechanisms for
inhibition of ABC transporters is an important goal if we are to translate
this basic research problem into a clinically important discovery.
Do you foresee any social or political implications
for your research?
Any ways that we can devise to inhibit ABC transport function has the
potential to help the human condition, either by decreasing bacterial
virulence or improving drug delivery to cells.
Amy L. Davidson, Ph.D.
Department of Chemistry
West Lafayette, IN, USA Web