Team:CCU Taiwan
Team:CCU Taiwan/Implementation
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Antibiotic-resistant bacteria are a threat to global health and development. According to global statistics, antibiotic-resistant bacteria cause the death of at least 700,000 people per year. Without urgent action, this number is projected to increase exponentially [1]. |
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The World Health Organization (WHO) warns that, without urgent action, antibiotic-resistant infections could cause 10 million deaths each year and losses of up to 100 trillion U.S. dollars by 2050 [2]. |
The source of these infections is bacteria resistant to three or more antibiotics, the so-called superbugs. Methicillin-resistant Staphylococcus aureus (MRSA), one of the best-known superbugs, can cause bacteremia and cardiovascular failure, resulting in severe organ damage and even death. At its peak, MRSA caused 19,000 deaths per year. MRSA arises from the improper application of antibiotics, such as unauthorized termination or extension of treatment. As proof, the infection rate of S. aureus has remained consistent over the past few decades, but the ratio of MRSA has increased year after year. |
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Typically, the skin efficiently defends against microbial infection, and the immune system fights microbes if wounds form on the skin. However, an open wound on a patient with a weak immunity increases the risk of microbe infection and needs further long-term antibiotic treatment, increasing the possibility of MRSA infection. For example, diabetic foot infections (DFI) are most frequently caused by S. aureus, and most of them are MRSA [3]. Similarly, acquired immunodeficiency syndrome (AIDS) weakens the immunity in patients and MRSA infections account for significant morbidity of AIDS patients. Moreover, MRSA can remain latent in macrophages, one of the major microbe cleaners of the human immune system, to escape antibiotic treatment and attack of the immune system. Together, MRSA infection and latency are emerging issues in medical centers and also in personal health care. |
Therefore, CCU_Taiwan iGEM team aims to provide a novel therapy to heal damage from MRSA through synthetic biology. We designed a novel antimicrobial dressing, in which we combine cell-penetrating peptides (CPPs) and antimicrobial peptides (AMPs) to target both intracellular and extracellular bacterial infections. The dressing designed by CCU_Taiwan is composed of three layers, including a protective outer layer, an absorptive middle layer, and an antimicrobial layer facing the wound. PU film is applied as the outer layer to provide structural strength, coating, and prevent further infection. The middle absorptive layer is composed of alginate and chitosan, which have hemostatic and exudate absorption characteristics. The antimicrobial layer contains collagen and antimicrobial agents attached to the collagen through the collagen binding domain (CBD). The antimicrobial layer can not only sterilize the wound but also prompt the formation of new tissue in the wound bed. |
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The proper release of antimicrobial agents, such as AMPs or TAT-AMPs, on the wound is important for control of bacterial infection. Thus, we add a collagen binding domain (CBD) from the FN1 gene in front of our antimicrobial agents to connect the antimicrobial agents with the collagen layer in our dressing. Next, it is well known that thrombin is activated to induce clotting during bleeding. Taking advantage of this, we insert a linker peptide with a thrombin cleavage site between CBD and the antimicrobial agents. Together, our design enables the thrombin-regulated release of AMPs or TAT-AMPs from the dressing. |
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Furthermore, we decided to make the public aware of the danger of MRSA through education, attacking the MRSA problem at the root. We launched a series of education promotions to educate the public regarding proper antibiotics usage and correct treatment of bacterial infection. We sought professional feedback from experts and participated in every collaboration opportunity possible. Due to the pandemic, these education promotions are published online. |
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