"Serendipitous occurrence could lead to development of a bacterial immunity shield against antibiotic-resistant strains"
In a significant breakthrough, researchers at Johns Hopkins Medicine have announced a potentially game-changing treatment for antibiotic-resistant bacterial infections. The study, led by Lloyd Miller, M.D., Ph.D., and his team, focuses on a novel approach called pancaspase inhibition, a form of host-directed immunotherapy.
The research, published in the journal Science Translational Medicine, targets the body's immune system against bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). The team's work was supported by grants from the National Institute of Allergy and Infectious Diseases, and the National Institute of Arthritis, Musculoskeletal and Skin Diseases.
Initially, the team was investigating the mechanisms behind MRSA skin infections in mice. However, their findings extend beyond this, as they successfully tested their pancaspase inhibitor against Streptococcus pyogenes and Pseudomonas aeruginosa, two dangerous skin bacteria.
The pivotal compound in this study is a pancaspase inhibitor called Q-VD-OPH. A single oral dose of Q-VD-OPH decreased the size of MRSA skin lesions and rapidly cleared the bacteria compared to vehicle-treated and untreated mice. Interestingly, the treatment worked whether interleukin-1β (IL-1β) was present or not, and without administering any antibiotics.
The success of this study lies in the inhibition of caspases, a family of enzymes that play crucial roles in apoptosis, or programmed cell death. Blocking caspases with Q-VD-OPH resulted in a rapid clearing of MRSA bacteria by keeping immune cells alive and boosting their protective function.
The research also revealed enhanced necroptosis of macrophages, mature monocytes that play a key role in defending the body against bacterial infections. This process, when activated, releases tumor necrosis factor, a protein that triggers bacteria-fighting immune cells to swarm into an infected area of skin.
It's important to note that Lloyd Miller is a full-time employee of Janssen Research and Development and has financial disclosures or conflicts of interest related to this study. The other authors of the study have no such financial disclosures or conflicts of interest.
The discovery of penicillin in 1928 by Alexander Fleming marked the beginning of the era of antibiotics. Now, over 90 years later, Miller expresses that the success of this study could mark the start of a second golden age of immunotherapy.
This groundbreaking research was conducted by a team that includes Jessica Rubens, Roger Ortines, Nicholas Orlando, Aman Patel, Dustin Dikeman, Yu Wang, Ivan Vuong, Daniel Joyce, Jeffrey Zhang, Mohammed Mumtaz, Halyun Liu, Qi Liu, Christine Youn, Garrett Patrick, Advaitaa Ravipati, Robert Miller, and Nathan Archer. The study's findings were included in a U.S. patent application (PCT/US2021/024889) through Johns Hopkins Technology Ventures.
This development offers hope for a future where antibiotic-resistant bacterial infections may no longer pose the threat they do today.
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