A
new study from Indiana University has revealed a previously unknown role a
protein plays in helping bacteria reel in DNA in their environment -- like a
fisherman pulling up a catch from the ocean.
The
discovery was made possible by a new imaging method invented at IU that let
scientists see for the first time how bacteria use their long and mobile
appendages -- called pili -- to bind to, or "harpoon," DNA in the
environment.
By
revealing the mechanisms involved in this process, the study's authors said the
results may help hasten work on new ways to stop bacterial infection.
"The
issue of antibiotic resistance is very relevant to this work since the ability
of pili to bind to, and 'reel in,' DNA is one of the major ways that bacteria
evolve to thwart existing drugs," said Ankur Dalia, an assistant professor
in the IU Bloomington College of Arts and Sciences' Department of Biology, who
is senior author on the study. "An improved understanding of this
'reeling' activity can help inform strategies to stop it."
The
act of gobbling up and incorporating genetic material from the environment --
known as natural transformation -- is an evolutionary process by which bacteria
incorporate specific traits from other microorganisms, including genes that
convey antibiotic resistance.
The
need for new methods to stop bacterial infection is growing since overuse of
existing antibiotics, which speeds how quickly infectious organisms evolve to
outsmart these drugs, is causing the world to quickly run out of effective
treatments. By 2050, it's estimated that 10 million people could die each year
from antimicrobial resistance.
Although
they may look like tiny arms under a microscope, Dalia said, pili are actually
more akin to an erector set that is quickly put together and torn down over and
over again. Each "piece" in the structure is a protein sub-unit
called the major pilin that assembles into a filament called the pilus fiber.
"There
are two main motors that had previously been implicated in this polymerization
and depolymerization process," added Jennifer Chlebek, a Ph.D. student in
Dalia's lab, who led the study. "In this study, we show that there is a
third motor involved in the depolymerization process, and we start to unravel
how it works."
The
two previously characterized "motors" that control the pili's
activity are the proteins PilB, which constructs the pili, and PilT, which
deconstructs it. These motors run by utilizing ATP, a source of cellular
energy. In this study, IU researchers showed that stopping this process, which
switches off the power to PilT, does not prevent the retraction of the pili, as
previously thought.
Instead,
they found that a third motor protein, called PilU, can power pilus retraction
even if PilT is inactive, although this retraction occurs about five times more
slowly. The researchers also found that switching off power to both retraction
proteins slows the retraction process to a painstaking rate of 50 times slower.
An unaltered pilus retracts at a rate of one-fifth of a micron per second.
Moreover,
the study found that switching off PilU affects the strength of pilus
retraction, which was measured by collaborators at Brooklyn College. The study
also showed that PilU and PilT do not form a "hybrid" motor, but
instead that these two independent motors somehow coordinate with one another
to mediate pilus retraction.
The
ability to precisely measure the pili's retraction rate -- and therefore
precisely measure the impact of altering the proteins that affect this process
-- was made possible by the ability to see pili under a microscope, which was
not possible until the breakthrough imaging method invented at IU.
"The
ability to fluorescently dye the pili was huge," Dalia said. "It
allowed us to not only see the pili's activity but also measure it in ways
which simply would not have been possible in the past."
Next,
Chlebek aims to learn more about how the pili still retract when the power is
switched off to both retraction motors, as well as explore how these insights
could apply to understanding pili activity in other strains of bacteria.
See:
Posted by Dr. Tim Sandle, Pharmaceutical Microbiology
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