A team led by engineering researchers at Dartmouth College has engineered a new antibacterial agent to essentially hide from the human immune system and treat life-threatening infections caused by MRSA and other types of S. aureus.
What is MRSA?
Methicillin-resistant Staphylococcus aureus (MRSA) refers to a group of Gram-positive bacteria that are genetically distinct from other strains of Staphylococcus aureus. MRSA is responsible for several difficult-to-treat infections in humans. A strain of S. aureus is celled MRSA when it has developed, through horizontal gene transfer and natural selection, multiple drug resistance.
The agent is the first lysin-based treatment with the potential to be used multiple times on a single patient which makes it ideal to treat particularly persistent drug-resistant and drug-sensitive infections.
This team described about this new agent in a paper which recently appeared in Science Advances.
S. aureus as mentioned can quickly gain resistance to antibiotic agents. Lysins which are basically enzymes naturally produced by microbes and associated viruses have shown potential to treat S. aureus in recent years.
“Lysins are one of the most promising next-generation antibiotics. They kill drug-sensitive and drug-resistant bacteria with equal efficacy, they can potentially suppress new resistance phenotypes, and they also have this laser-like precision,” said Karl Griswold, corresponding author and associate professor of engineering at Dartmouth.
The major problem with this treatment is the concern that lysins may prompt our immune systems to develop anti-drug antibodies, which can have negative side effects. To solve this problem, the team engineered and patented a new lysin based anti-bacterial agent named F12. This new agent hides from the human immune system (due to T cell epitope deletion), and therefore does not cause the same negative side effects as unmodified, natural lysins.
“We have engineered this super potent, super-effective anti-MRSA biotherapeutic, and we’ve done it in a way that renders it compatible with and largely invisible to the human immune system. By making it a safer drug, we’ve enabled the possibility of dosing multiple times in order to treat even the most highly refractory infections,” said Griswold.
The team will further study of F12 will examine synergy with standard-of-care antibacterial chemotherapies; preliminary results suggest the combinations are extremely potent and suppress drug-resistance phenotypes.
Hongliang Zhao, Seth A. Brooks, Susan Eszterhas, Spencer Heim, Liang Li, Yan Q. Xiong, Yongliang Fang, Jack R. Kirsch, Deeptak Verma, Chris Bailey-Kellogg, and Karl E. Griswold. Globally deimmunized lysostaphin evades human immune surveillance and enables highly efficacious repeat dosing. Science Advances, 2020 DOI: 10.1126/sciadv.abb9011