Biomedical Engineering Reference
In-Depth Information
treated wounds with sodium hypochlorite to enhance mechanical debridement
of dead tissue and slow bacterial regrowth to facilitate the healing process
(Carrel and Dehelly
1917
; Hirsch
2008
). Carrel's 227-page monograph described
in exquisite detail the decision-making process as to how to treat wounds and also
compared this strategy to others, such as those that make use of silver nitrate and
hydrogen peroxide. This combinational type of approach was particularly useful
during World War I, where wounds were common place and amputations were
often considered the only resort for severe wounds. However, it should be noted that
there were many who considered the use of antimicrobials in the debridement
process as being superfluous, especially in the treatment of war wounds. During
this time, Burghard, Leishman, Moynihan, and Wright wrote “the treatment of
suppurating wounds by means of antiseptics is illusory, and that belief in its efficacy
is founded upon false reasoning.” (Burghard et al.
1915
; Hirsch
2008
). However,
such opinion was not shared universally and in time it was recognized that com-
bining mechanical removal of dead material and associated biofilm with chemical
treatment was in fact beneficial. Interestingly, however, Burghard and colleagues
were actually right in their suggestion that the benefits conferred by antimicrobial
treatments can be limited, especially in the absence of other treatments, such as
mechanical removal. Why? Because undisturbed biofilm bacteria display properties
at the cellular and biofilm levels that individually and collectively contribute to
antimicrobial resistance.
Antimicrobials, whether antibiotics or biocides, represent the current mainstay
of most chemical treatment strategies to control biofilms. However, as hinted
above, most antimicrobials have a significant
Achilles' heel
; their effectiveness
against bacteria within undisturbed biofilms is significantly reduced when com-
pared to planktonic bacteria. This tolerance is due to changes in bacterial cellular
properties and the gross biofilm state (Fig.
2
). When considering the biofilm as a
whole, penetration of an antimicrobial can be hindered due to the expression of
extracellular polymeric substances that bind to the antimicrobial and/or by the
whole cells adsorbing or sequestering/inactivating the antimicrobial
(Xu et al.
1996
; Anderl et al.
2000
; Gilbert et al.
2002
). This effect can be further
enhanced in multispecies (polymicrobial) biofilms whereby one species preferen-
tially binds or removes a given antimicrobial and thus protects another species
(Leriche et al.
2003
; Schwering et al.
2013
). Conceivably, this would be enhanced
further if the two species were intimately associated in close proximity, as opposed
to distantly located within the same biofilm (Gilbert et al.
2002
). This failure to
Fig. 1
(continued) coadhesion) and also through nonspecific interactions. Recruited secondary
colonizing cells can be as single cells, coaggregates, or aggregates of genetically identical cells
(called autoaggregates). (
d
) Species within the developing polymicrobial biofilm expand and
component species interact. Interactions can be positive or negative and mediated, for example
in the expanded box, through the production and detection of cell-cell signal molecules.
Coaggregation interactions may enhance the close juxtaposition of interacting species through
adhesins expressed on one cell surface binding to cognate receptors expressed on a partner cell
surface. Multiple cell-cell signal molecules may be involved in the interaction (shown as
green
and
purple signals
). Diagram modified with permission from Rickard et al. (
2003
)
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