Unforeseen occurrence could potentially lead to development of antibiotic-resistant bacteria countermeasure
In a significant development, researchers at Johns Hopkins Medicine have discovered a potentially game-changing treatment for antibiotic-resistant bacterial infections. The research, led by Dr. Victor Nizet, involves a novel immunotherapy approach that targets the body's immune system against bacteria, bypassing the need for antibiotics.
The bacterium of note is methicillin-resistant Staphylococcus aureus (MRSA), a notorious antibiotic-resistant strain. The research team, which includes individuals from Johns Hopkins Medicine and external institutions, was initially studying the mechanisms behind MRSA skin infections in mice with and without the ability to manufacture interleukin-1 beta (IL-1β).
The breakthrough came with the use of pancaspase inhibition, a strategy known as host-directed immunotherapy. This approach proved successful against the tested bacteria, including MRSA, beyond its initial target.
The pancaspase inhibitor, when used, reduced apoptosis of neutrophils and monocytes, leaving them in plentiful numbers and better able to remove MRSA bacteria. This was achieved by blocking caspases, using a compound called Q-VD-OPH, which resulted in a rapid and remarkable clearing of MRSA bacteria by keeping immune cells alive and boosting their protective function.
Interestingly, the treatment worked whether IL-1β was present or not, offering a versatile solution that could potentially be applied broadly.
Dr. Miller, a full-time employee of Janssen Research and Development, expressed optimism that this discovery could mark the start of a second golden age in medicine, following the discovery of antibiotics by Alexander Fleming.
The study, published in the journal Science Translational Medicine, also saw enhanced necroptosis of macrophages, which are mature monocytes. This process, triggered by the destruction of macrophages, releases tumor necrosis factor (TNF), a protein that triggers bacteria-fighting immune cells to swarm into an infected area of skin.
The work was supported by grants from the National Institute of Allergy and Infectious Diseases, and the National Institute of Arthritis, Musculoskeletal and Skin Diseases. It's worth noting that Dr. Miller has financial disclosures related to this study, including grant support from several pharmaceutical companies, stock from Johnson & Johnson, and paid consultancy for AstraZeneca, Armirall, and Janssen Research and Development.
The researchers also tested Q-VD-OPH on Streptococcus pyogenes and Pseudomonas aeruginosa, two dangerous skin bacteria. A single oral dose of Q-VD-OPH decreased the size of MRSA skin lesions and rapidly cleared the bacteria compared with vehicle-treated and untreated mice.
Moreover, data from this study was included in a U.S. patent application (PCT/US2021/024889) through Johns Hopkins Technology Ventures for 'caspase inhibition as a host-directed immunotherapy against bacterial infections.'
This promising discovery offers a beacon of hope in the ongoing battle against antibiotic-resistant infections, potentially paving the way for a new era in medicine.
