Antibiotic Resistance of bacteria in biofilms

In biofilms, resistance seems to go hand and hand with multicellular strategies. Thus we look at features of biofilm infections, emerging mechanisms of resistance and how we can potentially treat. The inability for antibiotics to be used on biofilm based mechanisms is shown to have three separate hypotheses. First being slow penetration, second being the resistance of a phenotype and third is about an altered microenvironment.

The idea behind a biofilm in this study is to adhere to the biomaterial’s surface (catheters, prosthetic heart valves, etc.) that we use to help people with other diseases. This is dangerous because biofilm have bacteria inside that evade the host defenses and withstand antimicrobial chemotherapy. In laymans terms, it’s hard to kill the bacteria with medicine. Studies have shown that even those with adaptive and strong immune systems still have trouble resolving the bacterial infection. Susceptibility Tests have been shown to indicate that even when using bacterial treatment up to hundreds or even a thousand times the minimum inhibitory concentration, bacteria still manage to survive. The medicine kills the free floating bacteria but fails to wipe out the bacteria in-cased by the biofilm. Typically, the result of this infection then has to be surgically removed from the body.  The relevance of the understanding of antibiotic resistance of bacteria in biofilms to engineering because we consider that most of the bacteria that favor biofilms in the body are Pseudomonas aeruginosa or S epidermidis due to the ability to adept at forming biofilm, which mainly reside in our water, air, soil, or skin. The main objective of environmental engineers is focused on water and how to we process it. Considering this, Environmental Engineers can help monitor for the bacteria of interest.

Looking at the results we can compare to what was hypothesized from above. The idea behind Antibiotic Resistance of bacteria in biofilms is broken down into three separate ideas. The first hypothesis is a slow or incomplete penetration of antibiotics inside the biofilm itself. Using measurements of antibiotic penetration into biofilms, some antibiotics permeate (spread through) bacterial biofilms. However, it has also been shown that it is possible for the antibiotics to be deactivated in the biofilm. This would make penetration much more difficult or even impossible. The second hypothesis is that a subpopulation of microbes in the biofilm form unique and highly protective phenotypic-state much like spore formation. Test to show this hypothesis were shown by having support from studies that show resistance to newly formed biofilms that were too thin to pose a barrier from antibiotics. The third hypothesis was stated on the basis of how altered chemical microenvironment within the biofilms helped with protection. Biofilms are known to feature microscale gradients in nutrient concentrations. It has been found in studies using mini-electrodes that oxygen can be completely consumed in the surface layer of the biofilm. This then leads to anaerobic niches in deep layers of the biofilm. Concentration gradients in metabolic products then mirror substrates. Acidic waste then has the ability to increase the level of pH between the bulk layer and the biofilm. This is the part that will antagonize the action of the antibiotic. We know this is important because we know certain antibiotics work less efficient when in anaerobic conditions compared too aerobic. Also the depletion of a substrate could also cause some bacteria to enter a non-growing state, this is bad because certain antibiotics like Penicillin, target cell-wall synthesis which kill only growing bacteria.

Results relating to current practices help in the future of understanding biofilms because biofilm resistance depends on aggregation of bacteria in multicellular communities. One strategy might be to develop therapies that disrupt the multicellular structure of the biofilm. Some other potential therapies may include having an enzyme that dissolves the matrix polymers of the biofilm, using a chemical reaction to block biofilm matrix synthesis, and block microbial signaling that would interfere with cell to cell communication. This required for normal biofilms to function. We need to understand the multicellular nature of microbial life before treating the infections from biofilms.

Stewart, Philip S., and J. William Costerton. "Antibiotic resistance of bacteria in biofilms." The Lancet 358.9276 (2001): 135-138.