30 research outputs found

    Molecular Genetics of S. thermonitrificans ISP5579

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    The majority of commercially important antibiotic producing Streptomyces are mesophiles, grown at 25-3

    Evaluation of a library of FDA-approved drugs for their ability to potentiate antibiotics against multidrug resistant Gram-negative pathogens

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    The Prestwick library was screened for antibacterial activity or 'antibiotic-resistance breaking' (ARB) potential against four species of Gram-negative pathogens. Discounting known antibacterials, the screen identified very few ARB hits, which were strain/drug specific. These ARB hits included antimetabolites (zidovudine, floxuridine, didanosine, gemcitabine), anthracyclines (daunorubicin, mitoxantrone, epirubicin) and psychoactive drugs (gabapentin, fluspirilene, oxethazaine). This suggests that there are few approved drugs which could be directly repositioned as adjunct-antibacterials and these will need robust testing to validate efficacy. [Abstract copyright: © Crown copyright 2019.

    Creating an Antibacterial with in Vivo Efficacy: Synthesis and Characterization of Potent Inhibitors of the Bacterial Cell Division Protein FtsZ with Improved Pharmaceutical Properties

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    3-Methoxybenzamide (1) is a weak inhibitor of the essential bacterial cell division protein FtsZ. Alkyl derivatives of 1 are potent antistaphylococcal compounds with suboptimal drug-like properties. Exploration of the structure-activity relationships of analogues of these inhibitors led to the identification of potent antistaphylococcal compounds with improved pharmaceutical properties

    Alternatives to antibiotics-a pipeline portfolio review

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    Antibiotics have saved countless lives and enabled the development of modern medicine over the past 70 years. However, it is clear that the success of antibiotics might only have been temporary and we now expect a long-term and perhaps never-ending challenge to find new therapies to combat antibiotic-resistant bacteria. A broader approach to address bacterial infection is needed. In this Review, we discuss alternatives to antibiotics, which we defined as non-compound approaches (products other than classic antibacterial agents) that target bacteria or any approaches that target the host. The most advanced approaches are antibodies, probiotics, and vaccines in phase 2 and phase 3 trials. This first wave of alternatives to antibiotics will probably best serve as adjunctive or preventive therapies, which suggests that conventional antibiotics are still needed. Funding of more than £1·5 billion is needed over 10 years to test and develop these alternatives to antibiotics. Investment needs to be partnered with translational expertise and targeted to support the validation of these approaches in phase 2 trials, which would be a catalyst for active engagement and investment by the pharmaceutical and biotechnology industry. Only a sustained, concerted, and coordinated international effort will provide the solutions needed for the future.</p

    A new, large-bodied omnivorous bat (Noctilionoidea: Mystacinidae) reveals lost morphological and ecological diversity since the Miocene in New Zealand

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    A new genus and species of fossil bat is described from New Zealand's only pre-Pleistocene Cenozoic terrestrial fauna, the early Miocene St Bathans Fauna of Central Otago, South Island. Bayesian total evidence phylogenetic analysis places this new Southern Hemisphere taxon among the burrowing bats (mystacinids) of New Zealand and Australia, although its lower dentition also resembles Africa's endemic sucker-footed bats (myzopodids). As the first new bat genus to be added to New Zealand's fauna in more than 150 years, it provides new insight into the original diversity of chiropterans in Australasia. It also underscores the significant decline in morphological diversity that has taken place in the highly distinctive, semi-terrestrial bat family Mystacinidae since the Miocene. This bat was relatively large, with an estimated body mass of ~40 g, and its dentition suggests it had an omnivorous diet. Its striking dental autapomorphies, including development of a large hypocone, signal a shift of diet compared with other mystacinids, and may provide evidence of an adaptive radiation in feeding strategy in this group of noctilionoid bats
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