As antibiotic resistance becomes more of a challenge in the treatment of bacterial infections, and fewer new antibiotics are coming through the research pipeline, the biopharma industry is having to work hard to find alternative approaches. A piece published in May 2024 in Pharma Sources Industry Insights on The ongoing AMR challenge covered antibiotics, antibodies, bacteriophages and vaccines. This follow-up article focuses on alternatives to antibiotics, including antimicrobial peptides, faecal-based products, nanoparticles, pre-, pro-, post- and synbiotics, and other approaches. [1]
Creating an alternative: Antimicrobial peptides
Antimicrobial peptides (AMPs), first isolated from a soil Bacillus strain in 1939, have activity against viruses, bacteria, fungi and parasites. They may be synthetic or from natural sources, including bacteria, protozoa, fungi, plants, insects and animals. The antibacterial AMPs mostly act by targeting bacterial cell membranes and disintegrating the lipid bilayer. Others pass through the membrane and inhibit cell pathways, including DNA replication and protein synthesis. AMPs have potential in controlling biofilms and dealing with dormant persister cells, and bacteria appear to be less likely to develop complete resistance to AMPs. [2-4]
Examples of AMPs in development include:
· NovaBiotics is developing NP213 (Novexatin), which is based on the natural peptides found in nails and skin. This is in clinical trials for the treatment of nail disorders. [5]
· Soligenix is developing dusquetide (SGX943), an innate defence regulator (IDR). This acts by modulating the immune response rather than targeting the bacterium itself, which may reduce the risk of resistance. Dusquetide is in clinical trials for the treatment of antibiotic-resistant infections and may be used in combination with antibiotics. [6]
· The proteasome, which breaks down proteins in the cell, creates proteasome-derived defence peptides. In a mouse study, proteasome-derived defence peptides destroyed bacteria and improved survival rates in mouse models of pneumonia and sepsis. They could have potential as therapeutics in infectious disease. [7]
Using the body’s own bacteria: Faecal microbiota transplants
The use of faecal microbiota transplants (FMT) from a healthy donor to the gastrointestinal (GI) tract of someone with a GI disorder goes back to fourth century China when a suspension of human faeces was used to treat food poisoning and severe diarrhoea. The approach re-emerged in 1958 when rectal administration of donor faeces was used to treat four patients with pseudomembranous colitis, and again in 2008 during a Clostridioides difficile (previously known as Clostridium difficile) infection pandemic. [2]
In FMT, a suspension of commensal bacteria-containing faeces from a health donor is administered intestinally via a colonoscopy or enema, or using a nasogastric or nasoduodenal tube. It has proven effective in treating and preventing C difficile infection (CDI) following antibiotic treatment in adults, and in reinstating gut microbial diversity and functionality. [2]
In 2023, The FDA approved the first orally administered faecal microbiota product for the prevention of recurrence of C difficile infection. Known as Vowst (SER-109), the capsule was developed by Seres Therapeutics. [8] Seres Therapeutics is also developing SER-155, a biotherapeutic made up of a mixture of commensal bacteria, and has carried out a Phase Ib study. SER-155 has been designed to decolonize GI pathogens, improve epithelial barrier integrity, and induce immune tolerance to prevent bacterial bloodstream and AMR infections as well as other pathogen-associated negative clinical outcomes in allogeneic hematopoietic stem cell transplantation (allo-HSCT) patients. [9]
Using nanoparticles to attack bacteria
Nanoparticles...
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