From Alzheimer’s to Zebrafish: Eclectic Science and Regulatory Stories 96
Despite popular belief, most microorganisms do not live as free-swimming or -floating
invaders in a liquid sea or move through our blood or lymphatic system. Neither do they
exist as discrete colonies growing tidily on agar plates in a laboratory. Bacteria in typical
lab cultures act nothing like the ones encountered in nature. Rather they occur as mixed
populations inside what are termed “biofilms.”1 Up to 99% of bacteria live this way. The
ability to form biofilms is one of the most remarkable characteristics of bacteria. This
mode of bacterial growth has attracted particular attention because many persistent and
chronic infections, including periodontitis, otitis media, biliary tract infections, lung and
prostate infections, kidney stones and endocardititis, as well as the colonization of medical
implants, are believed to be intrinsically linked to the formation of bacterial biofilms.2
Discovery
Biofilms were first discovered in 1978 in the clear water of a frigid mountain stream in
British Columbia by Dr. William Costerton and a team of scientists. They found few bac-
teria in the water but knew that billions upon billions nestled in the slime that formed in
the crevices of the streambed rocks.3 The slime bacteria were not just sitting idly they were
forming complex structures encased in a slippery substance they had extruded, which is
called an exopolysaccharide matrix.
During the discovery of microorganisms several hundred years ago, the study of the
microbial world concentrated largely on the characterization of planktonic or free-swim-
ming organisms. Even as late as the 19th century, when Robert Koch’s studies validated
the germ theory of disease, most scientists continued to envision bacteria as single cells
found in some kind of watery habitat. From the early 1980s, there has been increasing
appreciation that these organisms account for only a small portion of microbial life, and in
both natural environments and human disease, the bulk of microbes are found in a sessile
(without a stem) form in biofilms.4
Microbes in biofilms are nearly impossible to eradicate with conventional antibiot-
ics. In the past few years, medical researchers have discovered that the microorganisms
in biofilms depend on their ability to continually signal one another. This signaling may
play a key role in developing drugs, a topic that will be discussed in more detail below.
In retrospect, it is odd that investigators overlooked biofilm formation for so long. For
millennia, bacterial biofilms have been in evidence in the form of dental plaque, coatings
on rocks in riverbeds and the slime that materializes inside a flower vase.5 As far back as
1684, Antonie van Leeuwenhoek observed microbial flora in dental plaque. He also may
have been the first person to attest to their resistance when he discovered that rinsing his
mouth with vinegar did not affect the number of viable cells.
Biofilm formation by microbes may be the end result of 3.5 billion years or so of
trying to live in extreme environments where nutrients are sparse, temperatures are very
high, water is scarce, acidity is high or toxic agents threaten their very existence (as in the
human body).6
Characteristics
A “biofilm” can be defined as a community of microorganisms (multicellularity) that are
associated with a surface and typically enveloped in an extracellular matrix. The cells and
matrix can be arranged to form a complex architecture. The steps needed for formation are
as follows: the free-swimming cells alight on a surface, arrange in clusters and attach the
cells begin producing the extracellular matrix the cells signal one another to form a micro-
colony chemical gradients arise and promote the existence of diverse species and metabolic
states and finally, some cells return to their free living form, escape and form new colonies.7
In the natural environment and in most clinical and industrial settings, biofilms are
composed of many different species, sometimes numbering in the hundreds.8 Sometimes
one species feeds on the metabolic wastes of another, aiding them both.
Despite popular belief, most microorganisms do not live as free-swimming or -floating
invaders in a liquid sea or move through our blood or lymphatic system. Neither do they
exist as discrete colonies growing tidily on agar plates in a laboratory. Bacteria in typical
lab cultures act nothing like the ones encountered in nature. Rather they occur as mixed
populations inside what are termed “biofilms.”1 Up to 99% of bacteria live this way. The
ability to form biofilms is one of the most remarkable characteristics of bacteria. This
mode of bacterial growth has attracted particular attention because many persistent and
chronic infections, including periodontitis, otitis media, biliary tract infections, lung and
prostate infections, kidney stones and endocardititis, as well as the colonization of medical
implants, are believed to be intrinsically linked to the formation of bacterial biofilms.2
Discovery
Biofilms were first discovered in 1978 in the clear water of a frigid mountain stream in
British Columbia by Dr. William Costerton and a team of scientists. They found few bac-
teria in the water but knew that billions upon billions nestled in the slime that formed in
the crevices of the streambed rocks.3 The slime bacteria were not just sitting idly they were
forming complex structures encased in a slippery substance they had extruded, which is
called an exopolysaccharide matrix.
During the discovery of microorganisms several hundred years ago, the study of the
microbial world concentrated largely on the characterization of planktonic or free-swim-
ming organisms. Even as late as the 19th century, when Robert Koch’s studies validated
the germ theory of disease, most scientists continued to envision bacteria as single cells
found in some kind of watery habitat. From the early 1980s, there has been increasing
appreciation that these organisms account for only a small portion of microbial life, and in
both natural environments and human disease, the bulk of microbes are found in a sessile
(without a stem) form in biofilms.4
Microbes in biofilms are nearly impossible to eradicate with conventional antibiot-
ics. In the past few years, medical researchers have discovered that the microorganisms
in biofilms depend on their ability to continually signal one another. This signaling may
play a key role in developing drugs, a topic that will be discussed in more detail below.
In retrospect, it is odd that investigators overlooked biofilm formation for so long. For
millennia, bacterial biofilms have been in evidence in the form of dental plaque, coatings
on rocks in riverbeds and the slime that materializes inside a flower vase.5 As far back as
1684, Antonie van Leeuwenhoek observed microbial flora in dental plaque. He also may
have been the first person to attest to their resistance when he discovered that rinsing his
mouth with vinegar did not affect the number of viable cells.
Biofilm formation by microbes may be the end result of 3.5 billion years or so of
trying to live in extreme environments where nutrients are sparse, temperatures are very
high, water is scarce, acidity is high or toxic agents threaten their very existence (as in the
human body).6
Characteristics
A “biofilm” can be defined as a community of microorganisms (multicellularity) that are
associated with a surface and typically enveloped in an extracellular matrix. The cells and
matrix can be arranged to form a complex architecture. The steps needed for formation are
as follows: the free-swimming cells alight on a surface, arrange in clusters and attach the
cells begin producing the extracellular matrix the cells signal one another to form a micro-
colony chemical gradients arise and promote the existence of diverse species and metabolic
states and finally, some cells return to their free living form, escape and form new colonies.7
In the natural environment and in most clinical and industrial settings, biofilms are
composed of many different species, sometimes numbering in the hundreds.8 Sometimes
one species feeds on the metabolic wastes of another, aiding them both.