Team:Penn/BiofilmsOverview

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<h1>Overview</h1>
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    Bacteria are capable of surviving on many surfaces for extended periods of time, until conditions favor their growth. Recent research has discovered that many pathogenic bacteria are capable of forming resilient “biofilm” colonies that are difficult to eradicate and even more difficult to treat, especially when established within a patient. Many chemical approaches have been applied to preventing biofilm formation and surface fouling, especially in invasive devices such as catheters. However, these devices carry the drawback of loss of function over time (as a result of the depletion of antimicrobial elements from the surface). Furthermore, because the compounds that leach from the surface of chemical-based antimicrobials surfaces may be toxic not only to microbes but also human tissue, their safety in vivo is unknown.
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    We seek to investigate an alternative approach by seeding surfaces with a non-pathogenic, biofilm forming bacterium that would secrete antimicrobial peptides (AMP) that would inhibit subsequent colonization of the surface by pathogenic microbes. The advantages of this approach over traditional chemical treatments is that the surface would be capable of replenishing AMP levels, preventing loss of function over time. For our project we chose to utilize lysostaphin (lss), an enzyme that is capable of destroying the cell wall of Stapylococcus, a genus of bacteria that are responsible for a large proportion of hospital acquired infections, as well as capable of forming biofilms.
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    <a href="#">Drug Delivery</a>
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        <li><a href='/Team:Penn/DrugDeliveryOverview'>Overview</a></li>
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    <a href="#">Biofilms</a>
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This experiment is not without precedent. This concept was utilized in 1999 to produce a protective biofilm on steel to inhibit the growth of sulfate-reducing bacteria that would have otherwise corroded the steel. The results indicated that the protective biofilm that produced AMPs (Gramicidin S) delayed the onset of corrosion and inhibited the activity of sulfate reducing bacteria for up to 28 days when immersed in growth media, and up to 120 hours in continuously replaced media (i.e. a surface placed in a continuous flow of media).
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<p style="color:black">One of the most pervading diseases afflicting the lives of countless individuals is cancer. Current widespread therapies such as chemotherapy and radiation therapy are limited in their ability to serve as a highly successful cancer therapeutic due to their off-target effects. As a result, one of our projects aims to solve some of these problems of specificity through an effective synthetic system that stems from the field of optogenetics. By using a system that is controlled by light we will engineer bacteria so that it kills cancerous cells with increased specificity in three dimensions. First, the bacteria will be able to specifically target cancerous regions through the use of antibody mimetic proteins (DARPins) that bind to growth factors which are commonly found on the surface of cancer cells. Second, because the system is light-activated we will be able to increase specificity by temporally controlling the duration of the cancer treatment. Since we have the ability to determine the exposure of light to the region of the tumor, the times between doses can be easily controlled. Third, since this treatment strategy has the additional advantage of being spatially-controlled by light, the drug does not lyse normal, unaffected cells.
 
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Latest revision as of 09:38, 3 October 2012

Penn 2012 iGEM Wiki

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Overview

Bacteria are capable of surviving on many surfaces for extended periods of time, until conditions favor their growth. Recent research has discovered that many pathogenic bacteria are capable of forming resilient “biofilm” colonies that are difficult to eradicate and even more difficult to treat, especially when established within a patient. Many chemical approaches have been applied to preventing biofilm formation and surface fouling, especially in invasive devices such as catheters. However, these devices carry the drawback of loss of function over time (as a result of the depletion of antimicrobial elements from the surface). Furthermore, because the compounds that leach from the surface of chemical-based antimicrobials surfaces may be toxic not only to microbes but also human tissue, their safety in vivo is unknown.

We seek to investigate an alternative approach by seeding surfaces with a non-pathogenic, biofilm forming bacterium that would secrete antimicrobial peptides (AMP) that would inhibit subsequent colonization of the surface by pathogenic microbes. The advantages of this approach over traditional chemical treatments is that the surface would be capable of replenishing AMP levels, preventing loss of function over time. For our project we chose to utilize lysostaphin (lss), an enzyme that is capable of destroying the cell wall of Stapylococcus, a genus of bacteria that are responsible for a large proportion of hospital acquired infections, as well as capable of forming biofilms.

This experiment is not without precedent. This concept was utilized in 1999 to produce a protective biofilm on steel to inhibit the growth of sulfate-reducing bacteria that would have otherwise corroded the steel. The results indicated that the protective biofilm that produced AMPs (Gramicidin S) delayed the onset of corrosion and inhibited the activity of sulfate reducing bacteria for up to 28 days when immersed in growth media, and up to 120 hours in continuously replaced media (i.e. a surface placed in a continuous flow of media).

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