Antibiotics have been a key component of modern medicine for decades. A critical question is why not enough antibacterials are being developed to tackle the growing challenge of drug-resistant infections. While current innovation in the early preclinical pipeline is encouraging, the journey for any new antibiotic is burdened with multiple challenges across its early and late development path. In this viewpoint, we explore the barriers to antibiotic development and how the Wellcome Trust is addressing these problems and working toward developing long-term solutions to facilitate a sustainable R&D ecosystem.
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| http://dx.doi.org/10.1021/acsinfecdis.0c00094 | DOI Listing |
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KorB switching from DNA-sliding clamp to repressor mediates long-range gene silencing in a multi-drug resistance plasmid.
Nat Microbiol
January 2025
Department of Molecular Microbiology, John Innes Centre, Norwich, UK.
Examples of long-range gene regulation in bacteria are rare and generally thought to involve DNA looping. Here, using a combination of biophysical approaches including X-ray crystallography and single-molecule analysis for the KorB-KorA system in Escherichia coli, we show that long-range gene silencing on the plasmid RK2, a source of multi-drug resistance across diverse Gram-negative bacteria, is achieved cooperatively by a DNA-sliding clamp, KorB, and a clamp-locking protein, KorA. We show that KorB is a CTPase clamp that can entrap and slide along DNA to reach distal target promoters up to 1.
View Article and Find Full Text PDFChronic cough as a disease: implications for practice, research, and health care.
Lancet Respir Med
January 2025
Department of Allergy and Clinical Immunology, College of Medicine, Asan Medical Center, University of Ulsan, Seoul, South Korea.
RSV vaccines: an elixir for healthy ageing?
Lancet Infect Dis
January 2025
Usher Institute, University of Edinburgh, Edinburgh EH16 4UX, UK.
Comparative cardiometabolic safety and effectiveness of aripiprazole in people with severe mental illness: A target trial emulation.
PLoS Med
January 2025
Division of Psychiatry, University College London, London, United Kingdom.
Background: There is limited and conflicting evidence on the comparative cardiometabolic safety and effectiveness of aripiprazole in the management of severe mental illness. We investigated the hypothesis that aripiprazole has a favourable cardiometabolic profile, but similar effectiveness when compared to olanzapine, quetiapine, and risperidone.
Methods And Findings: We conducted an observational emulation of a head-to-head trial of aripiprazole versus olanzapine, quetiapine, and risperidone in UK primary care using data from the Clinical Practice Research Datalink.
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