Gram-negative bacteria, such as E. coli, are known to be the most virulent class of drug-resistant bacteria. This week, the UN General Assembly will convene a meeting with world leaders to discuss the growing threat of antimicrobial resistance to global health and food security.
A report produced by the Global Leaders Group on antimicrobial resistance in April highlighted the dire consequences of drug-resistant infections, which are estimated to be responsible for 1.27 million deaths annually. The report also projected that without significant measures to combat antibiotic-resistant infections, the annual costs to healthcare systems worldwide could reach $412 billion by 2035.
However, the World Health Organization has raised concerns about the dwindling pipeline of new antibiotics. Only 12 new antibiotics entered the market between 2017-2021, with just one capable of targeting all pathogens deemed critical by the WHO.
One of the obstacles to commercial antibiotic development has been the overprescription of antibiotics, which can harm both beneficial and harmful bacteria in the gut microbiome. This imbalance in gut bacteria has been linked to various health issues, including colorectal cancer, irritable bowel syndrome, and even depression.
Despite these challenges, new solutions are emerging, such as the development of "smart antibiotics" that selectively target pathogenic bacteria while sparing native gut microbes. Researchers have identified specific protein systems critical for the survival of pathogens but not commensal species, paving the way for novel drug targets.
One such smart antibiotic, called lolamicin, has shown promising results in targeting Gram-negative bacteria, the most resilient and virulent class of drug-resistant bacteria. This antibiotic inhibits a protein system crucial for the growth of Gram-negative pathogens while having a different protein sequence in commensal bacteria.
While academic labs continue to make scientific progress, there is a need for commercial incentives to drive antibiotic development. The low prices and sales volume of new antibiotics, coupled with restrictions on their use, have deterred large pharmaceutical companies from investing in this sector.
To address this issue, experts like Henry Skinner, CEO of the AMR Action Fund, advocate for high-income nations to adopt models that incentivize antibiotic development and guarantee returns on investment for pharmaceutical companies. This could spur investment in the field and encourage the private sector to take risks in developing new antibiotics.
Looking ahead, researchers like Paul Hergenrother are working with commercial partners to further develop smart antibiotics like lolamicin into patented drugs for clinical trials. Despite the challenges in the commercial landscape, there is optimism that next-generation antibiotics will offer significant health benefits and prove viable in the marketplace.