97
Multicellularity allows the bacterial cells in a biofilm to establish a relationship
through chemical (by soluble signals) and physical (by cell-to-cell contact) interactions.
Through these interactions, the cells can communicate with one another and coordinate
their activities for the benefit of the group.9 This communication depends upon signaling.
Signaling
During the past two decades, accumulated evidence has established that bacteria undergo
a cell differentiation program when they grow and proliferate on surfaces. The ability to
organize structurally and to distribute metabolic activities among the different bacteria of
the consortium demands a high degree of coordinated cell-to-cell interaction. Such interac-
tions involve cell-to-cell communication to adjust the various functions within a bacterial
community. These communication systems rely on small signal molecules to monitor
population densities in a process known as “quorum sensing.” Quorum sensing systems
provide bacteria with a regulatory mechanism that enables individual cells to respond
to the density of the population. Once a critical mass, or quorum, has been attained, cells
collectively induce the expression of particular phenotypic traits, which are not observable
with individual cells. (Phenotype is the outward appearance of genes.) Quorum sensing is
thus a particularly valuable mechanism for gene regulation in biofilms.10
Such communication capabilities are essential prerequisites for coordinating bacterial
activities. Signal molecules that are released by specialized cells modulate the activities
of other cells in the vicinity.11 In Pseudomonas aeruginosa (a gram-negative bacterium with
a thin cell wall surrounded by an outer membrane) and a broad class of similar bacteria,
the relevant signaling molecules are acylated homoserine lactone (AHL), which each cell
produces at a low level. Gram-positive bacteria, which have a thick cell wall, use peptides
for signaling.12
When enough cells assemble as the result of signaling, the concentration of these com-
pounds increases, which in turn triggers complicated changes in the activities of dozens of
genes. One of these genes, algC, is needed to synthesize alginate, the gelatinous polymer
that makes up much of the extracellular matrix.13 (A number of other genes, perhaps more
than 200, are also expressed during biofilm growth.14) The matrix is separated by channels
and interstitial voids to allow convective flow for transporting nutrients to interior parts
of the biofilm and removing waste products.
Colonization and Implant Infections
As mentioned above, there has been an increasing recognition of the role that microbial
biofilms play in human medicine, and it has been estimated that up to 65%of all human
microbial infections involve biofilms.15 In 2002 and 2003, the Centers for Disease Control
and Prevention listed seven national healthcare objectives over five years three dealt with
biofilms and associated diseases: reduce catheter associated adverse events by 50% among
patients in healthcare settings reduce targeted surgical adverse events by 50% and reduce
hospitalizations and mortality from respiratory tract infections among long-term care
patients by 50%.16
This has important consequences when treating an infection since we know that ses-
sile cells in biofilms display phenotypic traits dramatically different from those of their
planktonic counterparts, such as increased resistance to antimicrobial agents and protec-
tion from host defenses.
Most regulatory professionals are aware of the explosive growth in the use of
indwelling medical devices, including catheters, stents, implantable cardiodefibrillators,
pacemakers, prosthetic joints, shunts, heart valves, dialysis and intrauterine devices and
dental implants. Materials selected to fabricate these devices have mechanical properties
that allow them to perform their required physiological function without causing trauma
to surrounding tissues. They are not inert, however, and their surfaces are capable of
Biofilms—Their Role in Persistent and Chronic Infections
Multicellularity allows the bacterial cells in a biofilm to establish a relationship
through chemical (by soluble signals) and physical (by cell-to-cell contact) interactions.
Through these interactions, the cells can communicate with one another and coordinate
their activities for the benefit of the group.9 This communication depends upon signaling.
Signaling
During the past two decades, accumulated evidence has established that bacteria undergo
a cell differentiation program when they grow and proliferate on surfaces. The ability to
organize structurally and to distribute metabolic activities among the different bacteria of
the consortium demands a high degree of coordinated cell-to-cell interaction. Such interac-
tions involve cell-to-cell communication to adjust the various functions within a bacterial
community. These communication systems rely on small signal molecules to monitor
population densities in a process known as “quorum sensing.” Quorum sensing systems
provide bacteria with a regulatory mechanism that enables individual cells to respond
to the density of the population. Once a critical mass, or quorum, has been attained, cells
collectively induce the expression of particular phenotypic traits, which are not observable
with individual cells. (Phenotype is the outward appearance of genes.) Quorum sensing is
thus a particularly valuable mechanism for gene regulation in biofilms.10
Such communication capabilities are essential prerequisites for coordinating bacterial
activities. Signal molecules that are released by specialized cells modulate the activities
of other cells in the vicinity.11 In Pseudomonas aeruginosa (a gram-negative bacterium with
a thin cell wall surrounded by an outer membrane) and a broad class of similar bacteria,
the relevant signaling molecules are acylated homoserine lactone (AHL), which each cell
produces at a low level. Gram-positive bacteria, which have a thick cell wall, use peptides
for signaling.12
When enough cells assemble as the result of signaling, the concentration of these com-
pounds increases, which in turn triggers complicated changes in the activities of dozens of
genes. One of these genes, algC, is needed to synthesize alginate, the gelatinous polymer
that makes up much of the extracellular matrix.13 (A number of other genes, perhaps more
than 200, are also expressed during biofilm growth.14) The matrix is separated by channels
and interstitial voids to allow convective flow for transporting nutrients to interior parts
of the biofilm and removing waste products.
Colonization and Implant Infections
As mentioned above, there has been an increasing recognition of the role that microbial
biofilms play in human medicine, and it has been estimated that up to 65%of all human
microbial infections involve biofilms.15 In 2002 and 2003, the Centers for Disease Control
and Prevention listed seven national healthcare objectives over five years three dealt with
biofilms and associated diseases: reduce catheter associated adverse events by 50% among
patients in healthcare settings reduce targeted surgical adverse events by 50% and reduce
hospitalizations and mortality from respiratory tract infections among long-term care
patients by 50%.16
This has important consequences when treating an infection since we know that ses-
sile cells in biofilms display phenotypic traits dramatically different from those of their
planktonic counterparts, such as increased resistance to antimicrobial agents and protec-
tion from host defenses.
Most regulatory professionals are aware of the explosive growth in the use of
indwelling medical devices, including catheters, stents, implantable cardiodefibrillators,
pacemakers, prosthetic joints, shunts, heart valves, dialysis and intrauterine devices and
dental implants. Materials selected to fabricate these devices have mechanical properties
that allow them to perform their required physiological function without causing trauma
to surrounding tissues. They are not inert, however, and their surfaces are capable of
Biofilms—Their Role in Persistent and Chronic Infections