In a recent study, biochemists, microbiologists, drug discovery experts, and infectious disease doctors have teamed up and shown antibiotics are not always necessary to cure sepsis.
Instead of killing causative bacteria with antibiotics, the researchers treated infected mice with molecules that block toxin formation in bacteria. Every treated mouse survived.
The breakthrough study suggests infections in humans might be cured the same way.
The molecules cling to a toxin-making protein found across Gram-positive bacterial species, called AgrA, rendering it ineffective.
Treating mice with the therapeutic molecules effectively cured infections caused by methicillin-resistant Staphylococcus aureus (MRSA).
S.aureus is notorious for its ability to overcome even the most potent antibiotics. Its resistance arsenal is broad, limiting therapeutic options to treat infections.
In a mouse model of S. aureus sepsis, treatment with small molecules alone resulted in 100 percent survival, while 70 percent of untreated animals died.
The small molecules were as effective in promoting survival as antibiotics currently used to treat S. aureus infections. The molecules also appear to give antibiotics a boost.
Septic mice treated with a combination of the small molecules and antibiotics had 10x fewer bacteria in their bloodstream than mice treated with antibiotics alone.
For relatively healthy patients, such as athletes suffering from a MRSA infection, these molecules may be enough to clear an infection.
For immunocompromised patients, combination therapy with the molecules and a low-dose antibiotic may be in order.
The team suggests he antibiotic in the combination could be one to which the bacteria are resistant in monotherapy because our small molecules enhance the activity of conventional antibiotics, such as penicillin.
With support from the small molecules, previously obsolete antibiotics could reenter the clinic.
This could provide a partial solution to the looming, global threat of antibiotic resistance.
If available, antibiotics kill most bacteria, but a small number of bacteria with natural resistance survive. Over time, antibiotic-resistant bacteria multiply and spread.
By Centers for Disease Control and Prevention estimates, at least two million Americans get an antibiotic-resistant infection annually.
For some infections, effective antibiotics are no longer available. Disarming bacteria of disease-causing toxins represents a promising alternative to dwindling antibiotics.
Eliminating toxins free up the immune system to eliminate bacterial pathogens instead of antibiotics.
The small molecules work against multiple bacterial species.
The new study included preliminary experiments showing the molecules prevent three other bacterial species from killing immune cells.
The researchers are now working to commercialize both potential drugs.
Case Western Reserve University has issued a license to Q2Pharma, Ltd., a biopharmaceutical startup company in Israel, to perform additional preclinical studies and develop F12 and F19 for clinical trials.
Their initial trials will focus on patients suffering from systemic multi-drug resistant infections.
Menachem Shoham, Ph.D., associate professor of biochemistry at Case Western Reserve University School of Medicine, is the senior author on the study.
The study is published in Scientific Reports.
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Source: Scientific Reports.
