March 8, 2004
Research on cholera bacteria focuses on biofilm
Bacteria in biofilms are much more resistant
than free-floating cells to antibiotics and disinfectants
By Tim Stephens
In regions where cholera is an endemic disease causing periodic seasonal
outbreaks, the bacterial pathogen (Vibrio cholerae) lives between
outbreaks in aquatic ecosystems such as coastal estuaries.
In cholera bacteria, the "rugose" variant (above) forms
biofilms that are more resistant to environmental stresses than
single cells (below) Photos: F. Yildiz
Little is known about how it survives and adapts to changes in its
aquatic habitat, but one factor is the cholera bacteria's ability to
switch from a free-floating "planktonic" mode to the formation
of slimy bacterial "biofilms" on various surfaces.
"Biofilms are thought to be a refuge for the organism, where it
is better able to survive stressful conditions," said Fitnat Yildiz,
an assistant professor of environmental toxicology at UCSC.
Yildiz's lab is investigating the molecular mechanisms that enable
cholera bacteria to switch between the two growth modes. She and postdoctoral
researcher Catharina Casper-Lindley reported their latest findings in
a paper featured on the cover of the March issue of the Journal of
The researchers have identified a new regulatory gene required for
the production of a mucus-like substance--an "exopolysaccharide"--that
is involved in biofilm formation. The exopolysaccharide attaches the
bacteria in a biofilm to each other and to surfaces.
"It is basically goop that the cells excrete and that forms the
matrix of the biofilm," Casper-Lindley said.
The newly discovered gene is the second such regulator of biofilm formation
found in cholera bacteria. Yildiz discovered the other regulatory gene
in previous work done at Stanford University. The findings suggest that
biofilm formation is controlled by a complex regulatory network of molecular
"We are now trying to understand the entire pathway--the interplay
between the regulators and other signaling molecules that enables the
bacteria to sense and respond to environmental conditions," Yildiz
In the laboratory, the two growth modes of V. cholerae correspond
to distinctive colony morphologies when the bacteria are grown on a
solid agar growth medium in petri dishes. The "smooth" variant
does not produce as much exopolysaccharide and does not form biofilms
as well as the "rugose" variant, in which the colonies appear
corrugated or wrinkled.
The environmental factors that trigger the switch from one growth mode
to the other are still unclear, but clues may be found in the regulatory
mechanisms Yildiz is studying. With a better understanding of the pathogen's
life cycle in its natural environment, researchers will be in a better
position to predict and control cholera outbreaks, she said.
In nature, biofilms enable the cholera bacteria to attach themselves
to a wide range of surfaces, including plankton and particles of sand.
Tiny crustaceans called copepods have been found to carry thousands
of cholera bacteria.
"These biofilms form on anything floating in the water, plankton
included," Casper-Lindley said.
Biofilm formation is also important in many other infectious bacteria.
Bacteria in biofilms are much more resistant than free-floating cells
to antibiotics and disinfectants such as chlorine. Similiar molecular
mechanisms are probably involved in regulating biofilm formation in
different organisms, Yildiz said.
"Whatever we find in cholera bacteria may be applicable to other
related pathogenic organisms, because biofilm formation is very important
in many bacterial infections," she said.
Yildiz's research is supported by the National Institutes of Health
(NIH), the Ellison Medical Foundation, and the UC Toxic Substances Research
and Teaching Program. She and other UCSC faculty recently received a
$258,000 NIH grant to fund the purchase of a special type of microscope--a
confocal microscope--needed to study biofilm formation.
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