Journal_1_2014_final_WEB

The biofilm challenge
Maria Alhede,
M.Sc., Ph.D
Morten Alhede,
M.Sc., Ph.D
Biofilm Test Facility
University of Copenhagen
Department of International
Health, Immunology
and Microbiology
Blegdamsvej 3B,
Bldg. 24.1.22,
DK-2200 Copenhagen
Denmark
http://biofilmtestfacility.
ku.dk
Correspondence:
malhede@sund.ku.dk
Conflict of interest: none
Abstract
The concept of biofilms has emerged in the
clinical setting during the last decade. Infections
involving biofilms have been documented in all
parts of the human body, and it is currently believed
that the presence of biofilm-forming bacteria
is equivalent to chronic infection. A quick
Pubmed search reveals the significance of biofilms,
as evidenced by a dramatic increase in scientific
publications on the topic, as well as in publications
concerning wounds with biofilms, which
reached 600 publications in 2013.
Judged from the number of publications, it
appears that biofilms play a significant role in
wounds. However, the impact of biofilms is often
debated, because infected wounds were also
treated before the concept of biofilms was coined.
In this short review, we will address the significance
of biofilms and their role in wounds, and
discuss the future tasks of the biofilm challenge.
Biofilms in short
Bacteria are found in at least two distinct states
– planktonic and sessile cells. Planktonic cells are
classically defined as “free flowing bacteria in suspension”
as opposed to the sessile biofilm state,
which is defined as “a structured community of
bacterial cells enclosed in a self-produced polymeric
matrix and adherent to an inert or living surface” 1 .
Figure 1. Total biofilm publications on
www.ncbi.nlm.nih.gov/pubmed/
Until the last decade, microbiologists have focused
and emphasized the planktonic state over the biofilm
state. However, the importance of the biofilm
mode of growth is becoming increasingly evident
with the availability of improved methods to study
sessile bacteria; hence the subsequent accumulation
of evidence for its widespread presence 2,3 .
Biofilms were discovered by one of the first
microbiologists, the Dutch scientist Antoine van
Leeuwenhoek, in the 1650s, but the actual breakthrough
regarding this phenomenon occurred
328 years later when Costerton and colleagues
published their work on “How Bacteria Stick” in
1978 4 . Since 1978, research on biofilm bacteria
has exploded (Figure 1).
It has now been established that most biofilmgrowing
bacteria cause chronic infections 5 , which
are characterized by persistent inflammation and
tissue damage 6 . These chronic infections, including
wound and foreign body infections, are
infections that “1) persist in spite of antibiotic
therapy and the innate and adaptive immune and
inflammatory response of the host and 2) which,
in contrast to colonization, are characterized by
the immune response and persisting pathology” 7 .
Traditionally, biofilms were considered as being attached
to a surface. However, in situ hybridization
(FISH) and confocal laser scanning microscopy
(CLSM) of different infection sites have shown
that the bacteria do not need to be attached to
surfaces to establish a chronic infection. Instead,
bacteria generate non-attached microcolonies by
aggregating with their fellow bacteria through matrix
components, and they appear to put up an
impenetrable barrier to host immune cells (e.g.,
phagocytic cells) 6,8-10 .
The challenge faced with regard to biofilms in
chronic infections lies in their significant tolerance
to treatment with antibiotics and to the host’s
immune response 11 . The antibiotic tolerance of
the biofilm has been investigated in numerous in
vitro models; these studies show that the biofilm
can withstand treatment with very high dosages of
antibiotics that are up to 1000 times the minimal
inhibitory concentration 12 .
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EWMA Journal 2014 vol 14 no 1