A novel peptide designed to disrupt bacterial defenses is poised to enter phase 3 clinical trials, offering a potential new weapon against the growing threat of antimicrobial resistance (AMR). The development, detailed in a recent review published in the British Journal of Biomedical Science, comes as researchers race to expand the pipeline of therapeutic options to combat infections increasingly immune to existing drugs.
AMR, described as a global public health crisis, is projected to cause approximately five million deaths annually and is forecast to reach ten million deaths per year by 2050 – exceeding the current death toll from COVID-19, according to the review. The crisis stems from the ability of viruses, bacteria, fungi, and parasites to evolve and resist antimicrobial treatments, largely driven by the overuse and misuse of antibiotics.
Zosurabalpin, the peptide entering phase 3 trials, specifically targets Acinetobacter baumannii, a bacterium frequently implicated in hospital-acquired infections and increasingly resistant to multiple drugs. The drug works by blocking the transport of lipopolysaccharide, a crucial component of the bacterial outer membrane, and is designed to circumvent existing resistance mechanisms.
The review highlights a surge in research exploring diverse therapeutic avenues beyond traditional antibiotics. Recently approved antibacterial drugs include gepotidacin, approved in 2025 for uncomplicated urinary tract infections, and lefamulin, approved in 2019 for community-acquired bacterial pneumonia. Combinations like Emblaveo (aztreonam/avibactam) and Xacduro (sulbactam/durlobactam) have gained approval to treat complex infections caused by gram-negative bacteria.
Researchers are also investigating the potential of antimicrobial peptides (AMPs), naturally occurring molecules found in various organisms. While over 3,000 AMPs have been discovered, only seven, all originating from soil bacteria, have been approved for use. Beyond peptides, antibacterial oligonucleotides – synthetic nucleic acid sequences that target bacterial RNA – are showing promise, with some formulations demonstrating antibiofilm activity in laboratory settings.
The search for solutions extends to unconventional sources. The review details ongoing research into the antimicrobial properties of honey, particularly Manuka honey, and even honeybee and spider venoms. Spices are also being investigated for their potential to enhance the effectiveness of conventional antibiotics.
Microbiome-based therapies, such as fecal microbiota transplantation (FMT), are gaining traction. The FDA approved Rebyota in 2022 and Vowst in 2023, both designed to restore healthy gut bacteria in patients with recurrent Clostridioides difficile infection. Studies suggest FMT may also help eliminate colonization of multidrug-resistant organisms in vulnerable patients, though further research is needed.
A particularly innovative approach involves predatory bacteria, like Bdellovibrio bacteriovorus, which actively hunt and kill other bacteria. These “living antibiotics” offer a potential advantage over traditional drugs, as their method of attack appears less susceptible to the development of resistance. However, this approach remains largely experimental.
Despite these advances, the review emphasizes that many novel strategies remain in early stages of development. Continued funding and collaboration across disciplines are crucial to translate these promising findings into clinical practice and address the escalating global threat of antimicrobial resistance.
