Download just slime

Survey
yes no Was this document useful for you?
   Thank you for your participation!

* Your assessment is very important for improving the work of artificial intelligence, which forms the content of this project

Document related concepts

Cheating (biology) wikipedia, lookup

History of biology wikipedia, lookup

Hologenome theory of evolution wikipedia, lookup

Genetic engineering wikipedia, lookup

Life wikipedia, lookup

Developmental biology wikipedia, lookup

Evolution of metal ions in biological systems wikipedia, lookup

Antimicrobial resistance wikipedia, lookup

Horizontal gene transfer wikipedia, lookup

Antibiotic use in livestock wikipedia, lookup

Biology wikipedia, lookup

Skin flora wikipedia, lookup

Dictyostelium discoideum wikipedia, lookup

Human microbiota wikipedia, lookup

Disinfectant wikipedia, lookup

Marine microorganism wikipedia, lookup

Microbial cooperation wikipedia, lookup

Bacterial taxonomy wikipedia, lookup

Biofilm wikipedia, lookup

Transcript
Features
Not
just
slime
Beneath the slipperyexteriorof a microbialbiofilm lies a remarkably
organizedcommunityof organisms
do the slippery,slimy
Whatcoating
on rocks in a
stream, the scum that
on
shower curtains and toilet
grows
bowls, and dental plaque have in
common? All are examples of
biofilms-structured communities of
microorganisms that adhere to surfaces. Wherever a suitable surface
and some water and nutrients are
available, biofilms are likely to grow,
their clusters of cells bound together
by a matrix of self-produced polysaccharides that gives these structures
their stickiness and sliminess.
The biofilm lifestyle provides
many advantages to the bacteria and
other microorganisms, including
fungi, archaea, and protozoans, that
may populate these sticky structures.
Organisms in a biofilm can get nutrients more readily than when they
live on their own, and they are protected from many of the insults of
daily life. And by sticking to a surface and forming biofilms, microorganisms can keep from being washed
away to a place where conditions
may be less hospitable-be it down a
stream or into the stomach.
Biologists and biology students
accustomed to seeing bacteria grow
in liquid-filled laboratory flasks may
wonder why bacteria form biofilms,
but biofilm researchers say that a
more appropriate question may be
"why not?" Indeed, mounting evidence suggests that, in the majority
of cases, a bacterium's natural tendency is to grow on a surface. "In the
real world, the vast majority of microbial growth is not occurring in
batch cultures, it is not occurring in
liquid-it is occurring on surfaces,"
by Elia T. Ben-Ari
September1999
says Roberto Kolter, a molecular
geneticist at Harvard Medical School
who studies biofilms.
The remarkable ability of bacteria to sense and rapidly respond to
their environment allows them to
switch back and forth between the
individual, "free-floating," or planktonic, state and the stationary biofilm
state. Whereas most microbiology
research has focused on planktonic
bacteria, "the more I investigate this,
the more I'm convinced that bacterial
cells are naturally at surfaces...and
[that] microbiologists have been
looking in the wrong place for 200
years," says James Bryers, a chemical
engineer at the University of Connecticut Health Center.
Although some early microbiologists did recognize that bacteria can
adhere to and grow on surfaces, the
concept of the biofilm as a biological
unit of organization did not emerge
until the 1970s. Rapid advances in
biofilm research have come in the
1980s and 1990s with the development of new technologies such as
confocal scanning laser microscopy,
which lets researchers view biofilms
in three dimensions (and in the fourth
dimension of real time), and new
molecular biology techniques, including specific probes that help researchers visualize individual cells or bacterial species within a biofilm.
Researchers now know that a
biofilm is not just a bunch of cells
stuck haphazardly to a surface but
rather an organized, cooperative
community with a distinct architecture. In a typical bacterial biofilm,
the cells are clustered together in
mushroom- and pillar-shaped structures with water channels between
them that let nutrients flow in and
metabolic waste products flow out.
The entire structure is enclosed in a
sticky mesh of polysaccharides and
proteins.
For better or worse
The ubiquity of these sticky communities of bacteria in the environment
and the many roles-both beneficial
and harmful to other organismsthat biofilms can play were not appreciated until relatively recently.
Chemical and environmental engineers and industrial microbiologists
were among the first to recognize the
importance of biofilms. For decades,
engineers have been deliberately cultivating particular bacterial biofilms
to break down contaminants in waste
water. More recent interest has focused on using biofilms for pollution
prevention and control, including
bioremediation of toxic materials in
soil and water. In nature, some
biofilms provide benefits to other
organisms-for example, by preventing the growth of harmful fungi on a
plant root or blocking the growth of
disease-causing microorganisms on
the surface of some human tissues.
But many biofilms have detrimental effects that are made much worse
because of their relatively high resistance to antibiotics, disinfectants, and
other antimicrobial agents. In industrial processes, for example, biofilms
can clog and corrode pipes and filters, contaminate food-processing
equipment, and foul the surfaces of
computer chips. Dental researchers
were the first to recognize that bacteria that stick to and grow on surfaces can cause health problems; the
biofilms that form dental plaque can
cause not only cavities but also gum
and periodontal disease.
More and more evidence suggests
689
University of California Press
is collaborating with JSTOR to digitize, preserve, and extend access to
BioScience
®
www.jstor.org
lar to the circulatorysystemof higher
organisms. And because one organism's waste productmay be another's
favoritefood, a biofilm consisting of
more than one species provides bacteria and other microorganismswith
an added advantage by facilitating
the exchange of nutrients.
Forminga biofilmcommunityalso
lets organisms establish a firm foothold near a good source of nutrients.
"For example, if you're stuck to a
tooth in the mouth,you areassuredof
an intermittentbut reliablesource of
nutrientsthat will be flowing past,"
says PhilStewart,a chemicalengineer
and deputy directorof the Centerfor
Biofilm Engineering, at Montana
State University. Biofilm formation
tends to be promoted when a particular nutrient is available in limited quantitiesor is diluted in a large
volume of water, Bryersnotes. The
structureandcompositionof a biofilm,
including its sticky coating, help to
source of some more severe, short- trap and concentrateessential nutriterm bacterial infections. "Bacteria ents for its microbial residents.
The safe harbor that a biofilm
in a biofilm existence can spawn off
non-biofilm bacteria...that can, when provides, shielding microorganisms
the conditions are right, cause an from the vagaries of the environacute infection," Greenberg explains. ment and from potential predators
or pathogens, such as amoebae or
viruses, is yet another benefit of life
Life in a biofilm
in such a community.Organismsin a
biofilm are also protected against
microordo
bacteria
and
other
Why
biofilm
the
ganisms adopt
lifestyle attack by a host animal's immune
on human tissues and elsewhere? system. The disease-fighting white
"Why is it better for groups of humans blood cells that can engulf and deto live in a village as compared to stroy an individual bacterium can[living as] scattered, wandering no- not tacklethe bulkymassof a biofilm,
mads?" Kolter asks in reply. The and antibodies tend to get stuck on
answer lies in the many benefits, the surfaceratherthan penetratinga
such as increased efficiency of services biofilm's interior.
Another noteworthy difference
and shelter from the outside world,
that life in a biofilm-like life in a between planktonic and biofilm bacteria is that cells within a biofilm are
human community-can provide.
The advantagesof life in a biofilm heterogeneous-for example,in their
also lead inevitably to analogies be- growth rates and metabolic status.
that biofilms are also responsiblefor
many chronic infections that are difficult, if not impossible, to eradicate-particularly in people with
weakened immune systems. A host
of medical problems are caused by
biofilms that flourish on nonliving
surfacesimplantedin the body, such
as catheters,contact lenses, artificial
joints, and other medical devices.
Biofilms can also grow on human
tissues, causing such chronic infections as endocarditis (inflammation
of the heart), the recurringlung infections that ultimately devastate
most people with cystic fibrosis, and
the middle ear infections that plague
many youngsters.
"Abiofilminfectionquiteoftencan
be a low-gradeinfection, an ongoing
aggravation that can be undetected
for prolongedperiods of time," says
Peter Greenberg,a microbiologist at
the University of Iowa. However,
biofilms may also be the indirect
tween biofilms and multicellular organisms or the tissues of higher organisms. For one thing, the organized
architecture of a biofilm, with its
network of channels, allows nutrients to be delivered to all the cells in
the community and provides for efficient removal of waste products, simi690
This heterogeneity makes bacteria in
biofilms more challenging to study
than planktonic bacteria. "Whereas
in a test tube that's mixed and being
shaken or a flask that's being stirred
we can say that this population of
bacteria is in a certain state, in the
biofilm we have to live with the fact
that we're dealing with a heterogeneous population,"Stewartsays. The
averagebacteriumin a biofilm grows
more slowly than a bacteriumliving
on its own. But within a biofilm,
Stewart says, "there are liable to be
bacteria that are growing rapidly
and...bacteriain zones in the biofilm
wherethey are growingslowly or not
at all, and those zones may be separated by only tens of micrometers."
Studies led by Zbigniew Lewandowski, at the Center for Biofilm
Engineering, use microelectrodesfine, needle-shaped chemical sensors-to probethe depthsof a biofilm
and measure the concentrations of
variouschemicals,includingoxygen,
sulfide, and hydrogen peroxide, in
differentareaswithin the film. These
experiments have revealed chemical
heterogeneity among different regions of a biofilm. The existence of
microenvironmentswithin a biofilm
may help explain phenomena such
as the variation in growth rates
among bacteria in the film and suggests that individual cells or species
within a biofilm may perform distinct functions.
Whatexactlyis a biofilm?
Although most researchersagree on
the general definition of a biofilm as
an organized community of microorganisms growing on a surface and
coated with polysaccharides, all
biofilms are not created equal. A
biofilm can be a single thin layer of
bacteria attached to the inside surface of a water pipe, or a "complex,
macroscopicallythick mat of organisms analogous to a forest ecosystem
on the microscopic level, with aerobic bacteria, fermenters,and sulfate
reducersall coexisting,"Stewartsays.
The nature of a biofilm may also
differ depending on whether it forms
on a living tissue or on nonliving
material such as a catheter, rock, or
mollusk shell. And whereas some
biofilms-for
example, most that
grow on implanted medical devicesconsist of only one or perhaps two
species of bacteria, others are comBioScience Vol. 49 No. 9
Bacterialbiofilms grow on both living and nonlivingsurfacesand arecomposedof mushroom-and pillar-shapedmicrocolonies,
as depicted in this model. Fluid flows through water channels between the microcolonies, carryingnutrients into the biofilm
and waste products out. Pieces of a mature biofilm may break off, float away, and establish new biofilms on other surfaces.
Illustration:Peg Dirckx, Center for Biofilm Engineering,Montana State University.
posed of many different bacterial
species as well as other microorganisms. Biofilms in the oral cavity are
notorious for their ability to harbor
many different species and genera of
microorganisms, and most biofilms
in the environment consist of multiple species.
Biofilm experts are hard pressed
to name a bacterial species that cannot form a biofilm. "Bacteria of all
stripes and all types, and also some
fungi, will form biofilms," Stewart
says. "There have been descriptions
in the literature of biofilms in environments ranging from very oligotrophic [low-nutrient] environments
to very eutrophic [nutrient-rich] environments, from deep sea hydrothermal vents at the bottom of the
ocean...to alpine streams," he says.
Indeed, even some bacteria that scientists thought could not grow as
biofilms, such as some common laboratory strains of Escherichia coli, are
able to form biofilms when grown
under the right conditions.
Nevertheless, some microorgan-
September1999
isms may be better than others at
forming biofilms. "Some people in
the biofilm community would argue
that almost all bacteria are capable
of forming biofilms and that's the
end of the story, but in fact we know
that some bacteria form much more
elaborate and much tougher biofilms
than other bacteria," Greenberg says.
For example, Pseudomonas aeruginosa forms a tenacious, difficult-totreat biofilm in the lungs of people
with cystic fibrosis, whereas another
troublesome bacterial pathogen,
Burkholderia cepacia, forms looser,
less organized biofilms and colonizes
the lungs of a smaller number of cystic
fibrosis patients, Greenberg says. He
and others hypothesize that B. cepacia
may be better at colonizing lungs that
have already been colonized with P.
aeruginosa because it can take advantage of the existing infrastructure of the P. aeruginosa biofilm to
form a dual-species biofilm.
The interactions that take place
among organisms in multi-species
biofilms are probably best understood
in the case of dental plaque. The
species composition of these complex biofilm communities changes
over time, and increasing species
complexity is associated with development of disease in the oral cavity,
notes Paul Kolenbrander, a microbiologist at the National Institute of
Dental and Craniofacial Research,
part of the National Institutes of
Health. "Presumably it's a succession of species [or] genera of bacteria, and each one contributes to that
site to make it available [and] advantageous to another group" in a manner analogous to the succession of
species that occurs in larger-scale
ecosystems, he says.
Microbiological studies by Kolenbrander and other dental researchers
have shown that a bacterial cell of
one species or genus will recognize
and attach only to cells of certain
other species. "Our data support [the
idea] that any bacterium that we
isolate from your mouth...would
have certain partnerships, and it's
likely that those partnerships are
691
beneficial in forming dental plaque,"
Kolenbrander says.
Using the knowledge of these specific coaggregation partnerships,
Kolenbrander and his colleagues plan
to assemble dual-species biofilms in
an experimental system that uses saliva-coated glass plates exposed to a
constant flow of saliva to mimic the
environment of the oral cavity. The
goal of these experiments is to use
molecular biology approaches to
learn how different types of bacteria
within a biofilm communicate with
one another and to identify specific
genes that are activated as a result of
this communication.
Ultimately, dental researchers
hope, such knowledge will lead to
new ways to control plaque development and prevent disease. Perhaps,
Kolenbrander says, "we could develop some way of doing a little
swish with some kind of liquid in the
morning and in the evening...that
would contain something that would
tell these bacteria to be quiet and
[that] it's not necessary to grow anymore," or that would even entirely
eliminate disease-causing bacteria
from the biofilm.
The life cycle of a biofilm
Whether they consist of a single species or multiple species, bacterial
biofilms go through distinct stages
of development. "Biofilm formation
is not the simple act of bacteria
bouncing at random on a surface,
getting stuck there, and just growing
there without differentiation," Kolter
says. "It's a very specific process that
is initiated by the bacteria sensing
environmental cues," including nutrient levels and temperature.
The first step in biofilm development is the attachment of a cell to a
surface. Different bacteria use different mechanisms to stick to surfaces, and recent studies of the cholera bacterium (Vibrio cholerae) by
Kolter and his colleagues have shown
that the specific molecules and pathways that this species uses for adhesion differ depending on whether the
692
surface is living or nonliving.
Studies of mutants of various
Gram-negative bacterial species in
Kolter's laboratory have also demonstrated that, for motile species of
bacteria, the propellerlike flagellum
is important for the initial interaction with the surface. Kolter speculates that flagellar motility may help
to overcome repulsive forces between
the surface being colonized and the
surface of the bacterium and may
also help break the biophysical barrier that exists at the liquid-solid
interface.
Once the cells have attached to
the surface, they begin growing and
multiplying and recruiting additional
planktonic cells from their surroundings. The cells then start moving
across the surface, first forming a
monolayer and then aggregating into
relatively small groups of bacteria
called microcolonies. These microcolonies then differentiate to form
the typical three-dimensional biofilm
structure with its protective polysaccharide coating.
Kolter and his colleagues have
evidence that microcolony formation, too, involves flagellar motility
in some Gram-negative bacteria. In
other motile Gram-negative species,
they found that a mechanism known
as "twitching motility"-mediated
by hairlike appendages called type
IV pili-plays a role in microcolony
formation. Kolter's lab is currently
doing genetic studies to identify the
mechanisms that are involved in
biofilm formation by several nonmotile species of bacteria.
In the final stage of the biofilm life
cycle, when a mature community
begins to age and get overcrowded,
chunks of the biofilm may break off
and float away to colonize new surfaces. Individual planktonic cells are
also continually detaching from mature biofilms and may establish new
biofilm communities on other surfaces. Indeed, Bryers says, the freefloating cells that microbiologists
typically find in water samples may
be cells that have temporarily and
only briefly left their normal, biofilm
state. "I think that's why we've gotten this illusion that cells float most
of the time-[because] those are the
ones that have been sampled," he
says. The usual mode of life for bacteria is in a biofilm attached to a
surface, "and what we are seeing
[when we sample the water] is their
children being tossed out of the house
and going downstream to set up shop
somewhere else," he says.
Cell signalingin biofilms
At least one stage of biofilm development is triggered by specific bacterial signaling molecules known as
quorum-sensing signals. These small
molecules were originally found to
be involved in triggering certain activities of bacterial cells-such as
bioluminescence in some marine bacteria and the production of virulence
factors in P. aeruginosa-that occur
only when the bacteria reach a certain
population density. When enough of
a bacterium's compatriots are nearby, secreted quorum-sensing signals
reach a critical concentration that is
sensed by the other bacteria, leading
to a coordinated change in behavior
that occurs via the activation of specific genes.
Last year, Greenberg and several
collaborators reported that acyl
homoserine lactone compounds,
which were already known to be
involved in several quorum-sensing
responses, are required for P. aeruginosa bacteria that have attached to a
surface and formed a monolayer to
differentiate into a mature biofilm.
P. aeruginosa mutants that do not
make the acyl homoserine lactone
signaling molecule form thin biofilms
that, unlike normal biofilms, are easily disrupted by a detergent.
This finding opens up the intriguing possibility that, by interfering
with signaling by acyl homoserine
lactones and other small molecules
now being found to play a role in
bacterial communication, researchers may be able to block biofilm
formation or break up biofilms that
have already formed. Experiments
BioScience Vol. 49 No. 9
with P. aeruginosa, which in addition to infecting the lungs of cystic
fibrosis patients can form biofilms
on catheters and other implanted
medical devices, have shown that "if
you knock out quorum sensing...the
organism becomes avirulent-it no
longer can cause infection," Greenberg says. However, whether the loss
of virulence results from an inability
to form biofilms is not yet clear.
Disrupting a biofilm might also
make bacteria more susceptible to
antimicrobial agents. Greenberg explains the potential power of this
approach by way of analogy: "In any
sort of military conflict, when you
attack, the first thing you want to do
is take out the opponent's communication systems. Once you've done
that, you make them vulnerable to
everything else you can do." He likens
traditional antibiotics to "big bombs"
from which bacteria in biofilms are
protected. But, Greenberg says, "if
we can wipe out the communication
system, then maybe the bombs will
be effective."
Mechanismsof resistance
The ability of biofilms to resist attempts to eliminate them-be it by
the immune system or by humancontrived means-makes them a huge
in a
problem. "Microorganisms
biofilm are remarkably resistant to
all kinds of antimicrobial challenges," Stewart says. "That's true
across the spectrum of biofilms, [and]
it's also true across the spectrum of
antimicrobial agents. We measure
biofilm resistance to brute force,
sledgehammer biocides like chlorine
bleach, and also to antibiotics that
have very specific targets."
Just how much more resistant to
antibiotics biofilm bacteria are than
their planktonic counterparts is difficult to determine, Greenberg notes,
because there are no standard laboratory methods for growing biofilms
or for measuring their antibiotic sensitivity. Estimates suggest that bacteria in biofilms are somewhere between 100 and 1000 times more
September 1999
antibiotic resistant than planktonic
bacteria.
Although the development of antibiotic resistance in planktonic bacteria is a growing concern, most acute
infections caused by such free-floating bacteria can still be eliminated
with antibiotics. By contrast, doctors are generally unable to eradicate biofilm infections. "We can improve the patient's condition with
high levels of long-term antibiotic
treatment, but when the antibiotic is
stopped, as often as not the bacterial
biofilm just grows back," Greenberg
says. Researchers hope that if they can
understand the mechanisms that account for this resistance, they will be
able to devise ways to overcome it.
Originally, researchers thought
that the polysaccharide slime that
surrounds a biofilm acted as a simple
physical barrier against antibiotics
and other antimicrobial agents. However, recent studies indicate that the
mechanisms of resistance are more
complex, possibly resulting from
both physical and biological differences between biofilm bacteria and
planktonic bacteria. The combination of these various mechanisms
may make biofilm infections particularly tricky to deal with.
One mechanism for resistance results from the ability of the polysaccharides on the biofilm's surface to
chemically inactivate some antimicrobials and antibiotics. As a result,
these compounds penetrate poorly
into biofilms. Resistance also occurs
because a significant proportion of
the bacteria within a biofilm are
growing very slowly or not at all,
making them resistant to killing by
the many antibiotics that work only,
or much more efficiently, against
growing cells.
More recent data suggest that-as
is the case for planktonic bacteriagenetic mechanisms also play a role
in biofilms' resistance to antibiotics.
Bryers and his colleagues have evidence that, compared to free-floating
bacteria, bacteria in biofilms can much
more readily exchange plasmids, circular pieces of DNA that carry genes
involved in antibiotic resistance. This
exchange of genetic material, Bryers
says, is stimulated in biofilms by
quorom-sensing signaling molecules
"that are being traded back and forth,
sort of like Chanel No. 5.... A cell
that doesn't have a plasmid can actually seduce one that does to come
close to it and trade genes with it."
Bryers believes that this rapid exchange of plasmids among cells in a
biofilm, which can occur both among
bacteria of a single species and across
species, can lead to the rapid spread
of antibiotic resistance throughout a
biofilm community.
Yet another possible genetic explanation for biofilm bacteria's increased resistance has recently come
to the fore. "It has become increasingly clear that there are whole sets
of proteins that bacteria express in
biofilms that aren't expressed when
they're not in biofilms," Greenberg
says. Bacteria "make special things
when they are organized in societies
that they don't make when they are
individual, nomadic bacteria. We
believe, although we don't know yet,
that some of those things are antibiotic resistance mechanisms."
Tackling the biofilm problem
This notion that biofilm bacteria are
genuinely different from their freefloating brethren in terms of their
patterns of gene expression has intrigued biofilm researchers. Preliminary evidence suggests that the early
steps of biofilm formation may trigger a new program of gene expression in bacteria, including production of the polysaccharides that form
the mucuslike extracellular matrix
of the mature biofilm.
"A cell that attaches is switched
into a different developmental pathway and is in some ways a different
creature than one that's free-floating, and that [difference] is genetically orchestrated," Stewart says.
This concept may lead to new approaches to fight bacteria in biofilms.
"If we recognize biofilm formation
as a biologically programmed pro693
Intheearlystagesof biofilmformation,bacteria
attach to surfaces and
form disperse monolayers.Here,Pseudomonas fluorescensbacteria
that were labeledwith a
molecularprobe bound
to greenfluorescentprotein are attachedto the
surfaceof a plant'sroot
hairs, which appearorange. Photo: Roberto
Kolter.
cess,thenallof a suddenwe havea whole
newlist of targetsfor
interfering with that
process. You might not need to kill in P. aeruginosa, a regulator gene
the cells anymore, you might just senses the environment at an earlier
needto learnhow to interfereat the stage of biofilm differentiation than
right stages of the developmental
cycleof thebiofilm,"hesays.Understandingthe detailsof how biofilms
form and what makes bacteriain
biofilmsdifferentmay also lead to
new ways to promote the growth of
desirablebiofilms.
Many ongoing studies focus on
understanding the signaling path-
waysinvolvedin biofilmdifferentiation and identifyingthe genes that
are activatedby these signals. Re-
cent work by Kolter and his col-
leagues,for example,indicatesthat
that mediated by the quorum-sensing signal identified by Greenberg
and his colleagues. Activation of this
gene, Kolter says, leads to a change
in the cells' motility behavior.
Greenberg's research group has
also been working to identify the
genes activated by quorum-sensing
signals in P. aeruginosa and to determine which of those genes are critical for biofilm maturation. One of
these genes codes for a compound
called pyocyanin, which is known to
be important for the virulence of P.
Bacteriawithin a biofilm grow at differentrates. In this side view of a frozen crosssection of a Klebsiella pneumoniae biofilm that has been stained with acridine
orange (a fluorescent dye), regions of relatively rapid growth appear orange and
regions of slower growth appearyellow or green. The biofilm was grown on a steel
surface (bottom of photograph), under turbulent flow conditions. Growth occurs
preferentiallyin the outer 30 micrometersof this biofilm, closest to the nutrientproviding fluid that surroundsit (top). Orange staining at the base of the biofilm
may be an artifact.The scale bar is 100 micrometers.Photo: Ching-TsanHuang and
Phil Stewart, Centerfor Biofilm Engineering,Montana State University. Reprinted
with permission from Biotechnology Progress 1996, 12: 316-321. ? 1996 American Chemical Society and AmericanInstitute of Chemical Engineering.
10
694
aeruginosa, and others constitute "a
big group of genes that look like they
encode a system for synthesis of some
sort of antibiotic" that could help
fend off other bacteria that may compete with P. aeruginosa to colonize a
surface, Greenberg says.
In addition to devising new ways
to control biofilms, researchers are
testing existing antimicrobial agents
that may have been dismissed as inferior for killing planktonic bacteria
to find out whether they are more
successful at killing biofilm bacteria.
"We may have good agents for controlling biofilms out there and just
not...know it, because all of the disinfectants, biocides, [and] antibiotics that we're using currently have
been selected and risen to the top in
tests against suspended bacteria,"
Stewart says.
Studies in Stewart's laboratory,
for example, have shown that hypochlorite-the active agent in chlorine bleach-is
largely ineffective
against biofilms because it is neutralized at the film's surface before it
can diffuse in. By contrast, a related
chemical, monochloramine (made by
mixing chlorine bleach and ammonia), which is a weak disinfectant in
tests on planktonic bacteria, was
more effective than hypochlorite on
a thick biofilm because it could penetrate the film.
Yet another avenue of research,
aimed at controlling the harmful
biofilms that form on nonliving surfaces, focuses on developing new
materials or surfaces that discourage
biofilm formation. "The holy grail
of biofilm control is the anti-fouling
surface-the Teflon of biofilm formation-that organisms simply don't
stick to," Stewart says. "Part of the
difficulty," he says, "is that any clean
surface that is placed into a real
environment will rapidly become
conditioned with a film of organic
molecules that mask the chemistry
of the surface."
The greatest prospects for success
in this area may be for biomaterials
used in medical devices, in part because funds are available to finance
BioScience Vol. 49 No. 9
..
the sophisticated chemistry that is
needed for such efforts. Bryers and
his colleagues, including collaborators at the University of Washington
in Seattle, have been working on a
variety of "situationally specific"
approaches that are designed to fight
biofilm formation by specific bacterial species known to cause infections of particular medical devices.
These approaches, Bryers says, include changing the surface properties of the biomaterial to make it a
"stealth material" that bacteria don't
see and that does not absorb the
proteins from body fluids that normally coat the surface and allow
bacteria to stick; filling the biomaterial with an antibiotic and then releasing the antibiotic in a slow, sustained manner so that it reaches
concentrations lethal to bacteria in
the proximity of the medical device;
and releasing selective anti-adhesion
molecules from the biomaterial that
prevent bacteria from sticking to the
surface.
One challenge that some biofilm
researchers see for the future is increasing the amount of collaboration between engineers and biologists in a field that is already more
interdisciplinary than most. Whereas
molecular biologists are interested
in looking for differences in gene
expression among the individual
bacteria within a biofilm, for example, chemical engineers may focus on the gradients of nutrients,
metabolic products, and other chemicals in biofilms and the transport
processes that underlie those gradients. "It's critical to understand
transport phenomena in the biofilm
at the same time that we're trying to
understand the genetics of what's
happening-they can't be divorced,"
Stewart says. "When we really put
the biology and engineering together,
0
we can do a lot."
k;K.
W.4.2N,
Smithsonian
Institution
Call
for
The American Institute of Biological Sciences
51st Annual Meeting
cosponsored with the Smithsonian Institution
BIOLOGY: CHALLENGES FOR THE
NEW MILLENNIUM
22-24 March2000
Washington, DC
will highlight major discoveries in biology made
The meeting
during the past century and will attempt to capture a perspective on the coming millennium'schallenges and opportunities, includingthe breakthroughs necessary to continue the advancement of biology.
Confirmedspeakers include:
Ernst Mayr, Peter Raven, Rita Colwell, Stephen J. Gould,
Gene E. Likens, Marvalee Wake, Gordon Orians,
Lynn Margulis, Daniel H. Janzen, Edward 0. Wilson
Approximately100 abstracts will be accepted for poster presentations at the meeting. Alldates and relevant informationcan be
found on the AIBS Web site:
http: //www.aibs.org/
meeting2000/
A limited number of posters will be accepted in each of the following areas: Evolution and Ecosystems, Biodiversity, Regulations, Energetics,Integration,Morphologyand Development, and
Behavior.
For more informationcontact: Mar/lynnMaury,Meetings Manager,
e-mail: [email protected],org
September 1999
695