Pseudomonas aeruginosa, shown here attached to an implant surface, is one of many resistant microorganisms.
Image credit: Dr. Laverty
Resistance to antimicrobials is one of the most pressing issues impacting society, resulting in at least 700,000 deaths worldwide per year. As the World Health Organization (WHO) emphasized in 2014, concerns are growing regarding increased resistance of microorganisms to current therapies.
The Centers for Disease Control and Prevention (CDC) estimate that drug-resistant bacteria cause 2 million illnesses and approximately 23,000 deaths each year in the US alone. Recognizing the severe threat to society, the US government released a 5-year, $1.2 billion national action plan in 2015 aimed at combating antibiotic-resistant bacteria.
The discovery of antimicrobials was responsible for increasing the safety of surgical interventions, advancing health care, improving quality of life and extending lives. However, there is a severe void in the development of new antimicrobial drugs. Resistant infections are responsible for high rates of morbidity and mortality, causing significant suffering to patients, their family and carers.
The discovery of antimicrobials was responsible for the introduction of surgical procedures and the advancement of health care. As resistance increases, so, too, does the possibility of an age where procedures such as joint replacements, cesarean sections, chemotherapy, implants and transplant surgery are not possible and simple infections kill.
The problem of implant-related resistant infections
Particularly problematic is the increasing prevalence of resistant infections associated with medical implants, such as hip replacements, heart valves and catheters.
The new peptide gel could revolutionize the treatment of superbug infections.
Image credit: Dr. Laverty
Not only do they require insertion through an operation - therefore coming with an enhanced risk of surgical wound infection - but the implant surface also provides an optimal environment for the attachment of microbial pathogens.
Microorganisms colonize the implant surface and become embedded in a protective slimy layer known as a biofilm. Once formed, microorganisms within the biofilm are protected from mechanical removal, immune clearance and exhibit an extremely high tolerance to antimicrobials.
This makes such infections difficult, if not impossible, to treat using conventional antimicrobial agents. Implant-associated infections are therefore a huge source of resistant hospital infections, contributing significantly to the spread of resistant microorganismsm such as Methicillin-resistant Staphylococcus aureus (MRSA), E.coli, Klebsiella pneumoniae and Pseudomonas aeruginosa.
Researchers at the School of Pharmacy, Queen's University Belfast in Northern Ireland, are designing medical materials of the future based on the natural building blocks of proteins and tissues: peptides.
Peptide gels show promising activity against superbugs
This promising strategy has led to the development of a peptide-based gel with the ability to selectively kill the most resistant hospital superbugs including MRSA, E.coli and Pseudomonas.
Peptides form the natural building blocks of human tissue and also play a major role in our immune response against infection. Therefore, they are excellent candidates for the design of innovative therapies and certainly have the potential to fill the current void in antimicrobial drug development.
Infection by superbugs including MRSA, E.coli and Pseudomonas can take a variety of forms, including skin and soft tissue infections, and at the surface of medical implants - such as catheters and hip replacements.
Our peptide gels show promising activity against all superbugs tested and have the potential to revolutionize the treatment of such infections. The properties that dictate a peptide's ability to form a gel are very similar to the principles that govern the selective activity of antimicrobial peptides against infection. Our ultimate aim is to have a platform that responds to infection development, selectively targeting the most resistant pathogens and providing long-term protection on surfaces such as implanted medical devices.
Much of our work was conducted in collaboration with the world-leading nanomaterials group (the Xu group) at the School of Chemistry, Brandeis University in Waltham, MA. Garry spent a research placement in 2013. Within Brandeis, Garry was able to learn more regarding how these building blocks formed tissue-like gels.
The chemistry behind their ability to form gels that mimic human tissue and target infection is exciting in itself, but the real challenge our group is focusing on is harnessing their potential as the next generation of therapies for the benefit of patients worldwide.
We have been successful in producing a series of very short peptide sequences which are easier to synthesize and more cost effective, compared with larger peptide and proteins used throughout biomedical research. They are more attractive to the pharmaceutical industry as it is cheaper to scale-up their manufacture and, therefore, they are more likely to be clinically translated for the benefit of patients.
Our research group at Queen's University Belfast are expanding the scope of applications for their molecules to include platforms for difficult-to-deliver drugs, tissue engineering, wound healing, anti-inflammatories and cancer therapies, in the hope of further breakthroughs.
Our molecules have many advantages over current synthetic materials used in health care. Peptides possess vast chemical versatility. This is proven by how they are harnessed throughout nature. They can be utilized to create materials with very specific functionalities and with the potential to attach a variety of molecules including drugs. In this way we are designing and creating biofunctional nanomaterials.