Resistance training: Micreos launches the first bacteria-killing enzyme against MRSA
Deaths from antibiotic resistance are an increasing threat. Dutch biotech company Micreos has launched what is said to the first bacteria-killing enzyme (endolysin) registered for human use against MRSA. Mark Offerhaus Micreos and Dr Bjorn Herpers clinical microbiologist, explain.
According to a UK government-commissioned report, the total number of deaths as a result of antimicrobial resistance is projected to rise to 10 million per year globally by 20501 – more than the number currently dying from cancer. The threat of antibiotic resistance is not new, the first reports of Staphylococcus sp. bacteria resistance to penicillin occurred in 1947, just four years after penicillin was first mass-produced, and Methicillin-resistant Staphylococcus aureus (MRSA), was discovered over 50 years ago.
Despite the size of the problem, investment in research and development is limited; the acute nature of bacterial infections makes trail design complex, and antibiotics are not particularly lucrative compared with treatments for chronic conditions. Also, fear of resistance has encouraged conservative usage of new agents.
Endolysins
With these challenges in mind, the holy grail is an agent which can sidestep bacterial resistance, or is viable for long term or prophylactic (preventative) therapy. The use of endolysins is one innovation which has this potential. Endolysins are an essential part of the reproduction process of phages. Phages are common micro-organisms which can replicate only through a bacterial host. When a bacterial cell is infected, the phage takes over its DNA and starts producing new phages. The phage uses endolysins, which are also produced inside the bacterial cell, to destroy the bacterial cell wall, releasing the new phages and killing the host bacterium.
Endolysins have three characteristics that assist in fighting antimicrobial resistance:
1) A working mechanism unrelated to that of antibiotics, meaning even antibiotic-resistant strains of bacteria, such as MRSA, are susceptible.
2) Phages have co-evolved with bacteria over billions of years; therefore, endolysins target highly-conserved areas of the bacterial cell wall, greatly reducing the likelihood of bacterial adaptation.
3) Endolysins target specific bacterial species; commensal (beneficial) bacteria are not killed, reducing the chance of opportunistic infection following treatment, as is often seen after courses of antibiotics.
Micreos’ endolysin, Staphefekt, is the first endolysin registered for human use against bacterial infections, and exemplifies the practical benefits of the characteristics of endolysins listed above.
Staphylococcus aureus is the most common cause of skin and soft tissue infections.2 Besides these more invasive infections, S. aureus can cause local symptoms like skin irritation, itch or inflammation. Staphefekt is currently used for treatment of skin conditions associated with S. aureus, like eczema, acne and rosacea. It’s effect is specific to Staphylococcus aureus, leaving the skin’s beneficial bacteria unharmed. Staphefekt has also not been shown to induce resistance in vitro, and does not have systemic side-effects when applied to the skin (unlike corticosteroids and antibiotics). It, therefore, has potential to be the first antibacterial compound suitable for longer-term maintenance therapy of S. aureus-related skin conditions and for large-scale prophylaxis.
The latest trials3 on rosacea and acne indicate a significant reduction in symptoms after Staphefekt use in the Gladskin gel or cream formulation. Compared with symptom severity scores before use, significantly less pustules, burning, itch, eye symptoms and dry skin were reported after 6 weeks in 112 people with rosacea, with a significant positive effect on the dermatological quality-of-life score. Similar results were found with acne, with significant reductions reported in lesions and pain in 59 people. Trials on eczema are ongoing, as S. aureus is known to be highly involved in this skin disease too. Furthermore, case observations in patients with recurring skin infections due to S. aureus suggest that long-term suppression of S. aureus carriage on the skin with Staphefekt could have a preventive effect on the frequency of local invasive infections like furunculosis.
Impact on pharmacoeconomics
As new antibacterial agents emerge which are viable as long-term maintenance therapies, or as prophylaxis, they will alter the clinical value and the pharmacoeconomic model for antibacterial treatments. With reduced fear of resistance, and removal of negative side-effects associated with broader disruption of the body’s natural flora, the remit of these drugs can expand, and their development will represent a better investment for pharmaceutical companies.
Phage and endolysin technology in other areas
Phage technology also has great potential outside of the pharmaceutical industry. Phages are already used for food safety. FDA-approved phage culture, Listex, specific to Listeria monocytogenes, is used during the production of meat, cheese, fish, vegetables, fruit and other food products, and Salmonelex, is used against Salmonella in poultry processing. Micreos’ pipeline also includes R&D projects in agriculture and animal health. These areas see heavy usage of antibiotics, and are seen as breeding grounds for resistance, so even here, the availability of antibiotic alternatives will have a positive impact on human health.
References:
1)Review on Antimicrobial Resistance. Tackling a Global Health Crisis: Initial Steps. 2015
http://amr-review.org/sites/default/files/Report-52.15.pdf
2)Moet, G et al. Contemporary causes of skin and soft tissue infections in North America, Latin America, and Europe: Report from the SENTRY Antimicrobial Surveillance Program (1998–2004) Diagnostic Microbiology and Infectious Disease; 57(1): 7-13
3)Micreos data on file