Scientists from Roche, a Swiss pharmaceutical company, have developed a new class of antibiotic that can kill a drug-resistant bacterium that poses a serious threat to human health. The new antibiotic, called Zosurabalpin, belongs to a family of compounds known as balpins, which target a key enzyme in bacterial cell wall synthesis. Zosurabalpin has shown potent activity against methicillin-resistant Staphylococcus aureus (MRSA), a superbug that causes infections that are difficult to treat with common antibiotics.
Balpins are a new class of antibiotics that were discovered by Roche scientists in 2019. They work by inhibiting the enzyme transglycosylase, which is essential for the formation of the bacterial cell wall. By disrupting the cell wall, balpins cause the bacteria to burst and die. Balpins are also able to penetrate the biofilms, which are protective layers of slime that some bacteria produce to shield themselves from antibiotics and the immune system.
Zosurabalpin is the most advanced balpin in Roche’s pipeline. It has a dual mode of action, meaning that it not only inhibits transglycosylase, but also binds to another enzyme called MurA, which is involved in the early steps of cell wall synthesis. By targeting both enzymes, Zosurabalpin interferes with two critical pathways in bacterial metabolism, making it harder for the bacteria to develop resistance.
Zosurabalpin Effective Against MRSA in Animal Models
MRSA is a type of Staphylococcus aureus that has become resistant to methicillin and other beta-lactam antibiotics, which are the first-line treatment for staph infections. MRSA can cause skin infections, pneumonia, sepsis, and other serious complications. According to the World Health Organization (WHO), MRSA is one of the 12 priority pathogens that pose the greatest threat to human health.
In a study published in the journal Nature, Roche researchers tested Zosurabalpin against MRSA in vitro and in vivo. They found that Zosurabalpin was able to kill MRSA strains that were resistant to multiple antibiotics, including vancomycin, daptomycin, and linezolid. Zosurabalpin was also effective against MRSA strains that had reduced susceptibility to balpins, suggesting that it has a unique mechanism of action.
The researchers also evaluated Zosurabalpin in two mouse models of MRSA infection: one that mimicked skin and soft tissue infection, and another that mimicked lung infection. They found that Zosurabalpin reduced the bacterial load and improved the survival of the infected mice, compared to the control group. Zosurabalpin also showed low toxicity and good pharmacokinetic properties in the animal studies.
Zosurabalpin: A Potential Breakthrough in Antibiotic Discovery
The discovery of Zosurabalpin is a significant achievement for Roche and the field of antibiotic research. Zosurabalpin is the first balpin to enter clinical trials, and the first new class of antibiotic to target MRSA in 50 years. Zosurabalpin could offer a new option for patients with life-threatening infections caused by drug-resistant bacteria.
Roche has initiated two phase I clinical trials to evaluate the safety, tolerability, and pharmacokinetics of Zosurabalpin in healthy volunteers. The results of these trials are expected in 2024. If successful, Zosurabalpin will advance to phase II trials, where it will be tested in patients with MRSA infections.
Roche is also exploring the potential of Zosurabalpin and other balpins to treat other types of bacterial infections, such as tuberculosis, gonorrhea, and Clostridioides difficile. Roche hopes that Zosurabalpin and other balpins will contribute to the global fight against antimicrobial resistance, which is one of the biggest challenges facing humanity.