Fighting Antibiotic Resistant Bacteria with Innovative Peptides and Nanocarriers
This is MRSA, one of a number of antibiotic resistant strains of bacteria. As the number of resistant strains of bacteria continue to grow, better treatment solutions need to be found. Image Source: Flickr User: NIAID
The fight for human life may be occurring on a far smaller scale than ever imagined. A number of pathogenic bacteria that were previously easily managed through antibiotic treatment are now nearly or entirely untreatable by conventional means. There are many reasons for this resistance, ranging from overuse of existing antibiotics to poor patient compliance with prescriptions to improper handling of antibiotic disposal. While researchers work to suss out the best way to handle these contributing factors, there remains an imminent need for effective therapeutics that will handle this burgeoning bacterial mutation crisis. By developing novel antibiotics and moving beyond traditional treatments into other therapeutics, such as peptides, researchers are beginning to see ways around this contentious issue in modern medicine. Antimicrobial peptides may be the solution researchers have been seeking for years, but have their own challenging properties, including delivery before degradation. The leap forward through these difficulties can be propelled by using modeling and simulation to better model and design therapeutics in silico before moving to the bench.
Looking Beyond Traditional Antibiotics
As is quickly becoming obvious, antibiotics just aren’t cutting it when it comes to fighting off many of the currently recognized superbugs. Researchers are working away at new classes of antibiotics, but this is proving to be vastly challenging. What if investigators looked beyond a classic antibiotic paradigm completely? In recent years, the use and research of antimicrobial peptides (AMP) has been gaining more traction. AMPs may be either natural or synthesized, and to date, more than 5,000 have been investigated.1 Although there are four main classifications of AMPs, α-helix, β-sheet, extended and loop, α-helix and β-sheet are most common, with α-helical peptides being the most studied. Fortunately, these are well known and recognized structures within microbiology and can be easily modelled with innovative software, allowing researchers to assess their approximate reactivities and potential target interactions.
While antibodies tend to target cellular activities, such as metabolism or DNA synthesis, AMPs go straight for the lipopolysaccharide layer of the cell membrane. This is a ubiquitous trait amongst microorganisms and allows for AMPs to have little effect on eukaryotic cells, as they are high in cholesterol and have low enough anionic charges to be ignored. This takes a lot of the worry out of the design of this class of therapeutics. Additionally, it may mean that peptide based antibiotic therapies won’t succumb to the same fate as antibiotics quite as quickly; it is a greater leap for the major structural components of a bacteria to shift and mutate, as compared to smaller mechanisms within the cell itself. Regardless, if resistance does become a factor, there are over 5,000 other candidates waiting in the wings. Because of this high volume of potential candidates, it is important that researchers are able to efficiently sift through lab and clinical data, identifying potential overlapping mechanisms to avoid reproducing antibiotic therapies that are ineffective.
It’s All in the Delivery
AMPs have a lot of potential, but there is a catch. They are broken down with an unfortunate efficiency within the human body, making speedy delivery a must. Fortunately, there have been many recent advances in the world of drug delivery. As detailed in a recent post, scientists have harnessed the power of viral capsids and will likely use them for drug delivery and as bioreactors in the coming years. The current approach to peptide antibacterial therapies is nearing this type of innovation, as well.
In a collaborative effort between labs and sciences, researchers have worked together to create an effective AMP, and the nanocarrier to deliver it.2 This protective shell ensures that the peptide is delivered, without degradation, to where it needs to go, and it also intesifies its effect at the active site itself. Researchers have stated that moving forward they would like to incorporate a programmed release into the nanocarriers they develop, which leaves the field wide open for in silico development and could be the answer we need to address antibiotic resistant bacteria.
BIOVIA Biologics Discovery fills that technological need. It is a common platform with capabilities that can move a therapeutic from pre-bench development to clinical trials. With predictive analytics, peptide modelling, workflow and data management, this technology is what is needed to move these projects forward. “Programming” a nanocarrier will be no easy feat, but by mining into already accrued data and manipulating proposed experiments within a modelling environment, researchers are more likely to have success more quickly. Biologics Discovery’s capabilities in pre- and post-discovery modelling save investigators time and R&D dollars. Please contact us today to learn more about how our software options can support the efforts of your lab.
- “Antimicrobial Peptides,” November 28, 2013, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3873676/ ↩
- “Antimicrobial Peptide-Driven Colloidal Transformations in Liquid-Crystalline Nanocarriers,” August 19, 2016, http://pubs.acs.org/doi/abs/10.1021/acs.jpclett.6b01622 ↩