Biofilms in Disease - Antibiofilm Agents: From Diagnosis to Treatment and Prevention - page 6

but because human matrix proteins soon cover any foreign device in the human
body, this form of attachment likely only plays a minor role even in device-
associated biofilm infections. In the case of motile bacteria, such as
P. aeruginosa , attachment may be preceded by active motion toward the surface,
whereas nonmotile bacteria have to rely on passive modes of motion in that first
step of biofilm development.
After attachment is accomplished, the bacteria proliferate and surround them-
selves with the characteristic biofilm matrix. This matrix is composed of many
different molecules. Some are specific to the given bacterium, such as the
exopolysaccharides and secreted proteins produced by many biofilm bacteria.
Others may be produced by a large subset of bacteria, such as teichoic acids
found in Gram-positive bacteria. As biofilms are in a stationary mode of growth,
the biofilm matrix also comprises molecules that are released from dying cells. In
particular, extracellular DNA (eDNA) was found to contribute to the biofilm matrix
in many bacteria (Whitchurch et al. 2002 ). Electrostatic interactions between
oppositely charged matrix polymers are believed to play a key role in matrix
formation. It needs to be stressed that for some of these molecules, evidence for a
participation in the biofilm matrix is only derived from in vitro investigation, such
as in the case of eDNA. The environment in the human host contains factors, such
as nucleases and proteases, which have the potential to interfere strongly with the
composition of the biofilm matrix. Especially eDNA may be degraded by the
efficient human serum DNaseI (Whitchurch et al. 2002 ). It may be because the
human host cannot degrade them that biofilm bacteria produce specific biofilm
exopolysaccharides, several of which have a proven function in in vivo biofilm
formation (Rupp et al. 1999 ; Conway et al. 2004 ; Hoffmann et al. 2005 ).
Were it only for the biofilm matrix components, biofilms would be unstructured
“clumps” of cells, and expansion of a biofilm would hardly be possible without
leaving cells in deeper layers prone to death due to limited nutrient availability.
However, we know from microscopic analysis that biofilms have a characteristic
three-dimensional structure with cellular agglomerations in “mushroom” shape and
channels that provide nutrients to those deeper layers. The molecular factors that
facilitate channel formation have recently gained much attention. Several biofilm-
forming bacteria were found to produce surfactant molecules to structure biofilms
in that fashion (Otto 2013 ). Notably, the same forces that underlie channel forma-
tion are responsible for the detachment of cell clusters from a biofilm, a mechanism
that leads to dissemination of the pathogenic bacteria to the bloodstream, and thus
may cause second-site infections.
Biofilm formation is under the control of a series of regulatory systems, which
often differ considerably between different biofilm-forming bacteria. However,
there are also generally applicable concepts in biofilm regulation. In several
bacteria, such as E. coli , sensory and regulatory systems trigger biofilm develop-
ment upon contact with a surface (Otto and Silhavy 2002 ). Furthermore, the general
switch from the planktonic to the biofilm mode of growth is often under control
of the second messenger cyclic di-GMP (Romling et al. 2013 ). Finally, cell