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Center for Biofilm Engineering
Biofilm Control/Antimicrobials
Research Area
 The
biofilm control team addresses
issues related to improving control of detrimental biofilms.
Our work is motivated by the nearly universal observation that
microorganisms growing in biofilms are less susceptible to all types of
antimicrobial agents than the same microorganisms when grown in
conventional suspension cultures. Our scientific approach is to
investigate the fundamental physical, chemical, and biological
mechanisms that protect biofilm
cells from antimicrobial challenges compared to their free-floating
counterparts. We also conduct applied research for industrial
sponsors in a number of projects.
Goals:
- Explain quantitatively the penetration of antimicrobial agents into
biofilm.
- Characterize the nutrient-limited physiological state(s) of biofilm
microorganisms and relate these starved physiological states to
antimicrobial resistance.
- Investigate the possibility of a distinct and protected biofilm
phenotype.
- Integrate these constituent resistance phenomena in mathematical
models.
- Apply these insights to develop improved technologies for biofilm
control.
Highlights:
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Transport Limitations to Antimicrobial Agent Efficacy
We have shown that limited antimicrobial penetration into biofilm does
happen and can dramatically decrease biofilm susceptibility. This
mechanism is operative when the antimicrobial agent is reactively
neutralized in the surface layers of the biofilm faster than it diffuses
into the biofilm. On the other hand, when the antimicrobial agent is
not particularly reactive with biofilm constituents, the agent penetrates
readily. Click here for publications related to
transport limitations to
antimicrobial efficacy. |
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Physiological Limitations to Antimicrobial Efficacy Against Biofilms
If a nutrient becomes limiting in the interior of a biofilm microcolony,
the microorganisms in that region will be forced into a slow-growing or
non-growing state. It is well known that starved bacteria can be
much less susceptible to a variety of antimicrobial challenges. We
are developing techniques to characterize the physiological heterogeneity
of biofilm to enable us to test this hypothesis. We have
demonstrated pronounced physiological heterogeneity in biofilm using
fluorescent staining techniques. Click here for publications related to
physiological limitations to
antimicrobial efficacy. |
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Electrical Enhancement of Antimicrobial Efficacy against Biofilm
When a weak direct current is applied to a biofilm during treatment with
an antibiotic, killing efficacy is remarkably enhanced. We
have shown that, in the case of Pseudomonas aeruginosa treatment
with tobramycin, the enhancement in antibiotic efficacy is probably due to
the electrolytic generation of oxygen. We are working with
collaborators to develop commercial applications of the "bioelectric"
technology for medical instrument sterilization. Click here for
publications related to electrical
enhancement of antimicrobial efficacy.
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Modeling Biofilm Antimicrobial Resistance
We have developed several mathematical models that can explain biofilm
resistance to antimicrobial agents based on quantitative descriptions of
fundamental constituent processes such as diffusion, disinfection, and
microbial growth. Phenomena that these models can predict include
profoundly retarded penetration of reactive antimicrobial agents, poor
biofilm efficacy of growth-rate dependent antimicrobial agents, and the
characteristic signature disinfection profile of a resistant biofilm
phenotype. Click here for publications related to
modeling biofilm antimicrobial resistance.
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Biofilms do not follow the same rules that free-floating microbes do when
it comes to antimicrobial treatments. This figure shows how planktonic and
biofilm cells of Pseudomonas aeruginosa respond differently to
exposure to chlorine. One difference that is immediately obvious from this
graph is that killing rates of cells in the biofilm are always lower than
those for planktonic bacteria. A second difference is that increasing the
concentration of chlorine does more to improve the killing rate against
biofilm bacteria than it does for planktonic cells. We have measured a
similar phenomenon with other antimicrobials including glutaraldehyde, a
quaternary ammonium compound, and DBNPA. The practical suggestion that
follows from this work is that biofilms are most effectively treated with
a relatively high concentration of antimicrobial. A concentrated dose,
even if brief, will tend to be more effective than a prolonged treatment
of lower concentration. |
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Search by topic area for publications in this area.
See CBE publications
search.
Click here for more detail on
mechanisms of antimicrobial resistance
For more information, email
Dr. Phil Stewart.
24 June, 2008
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