Publications (2018-2020) Utilisation of the Prestwick Chemical Library to identify drugs that inhibit the growth of mycobacteria
Kanvatirth, P., Jeeves, R. E., Bacon, J., Besra, G. S. & Alderwick, L. J.
PLoS One 14 (2019)
Tuberculosis (TB) is an infectious bacterial disease that kills approximately 1.3 million people every year. Despite global efforts to reduce both the incidence and mortality associated with TB, the emergence of drug resistant strains has slowed any progress made towards combating the spread of this deadly disease. The current TB drug regimen is inadequate, takes […]
Publications (2018-2020) Identification and characterization of menadione and benzethonium chloride as potential treatments of Pierce’s disease of grapevines
Zhang, S., Jain, M., Fleites, L. A., Rayside, P. A. & Gabriel, D. W.
Phytopathology 109 233–239 (2019)
Xylella fastidiosa infects a wide range of plant hosts and causes Pierce’s disease (PD) of grapevines. The type 1 multidrug resistance (MDR) efflux system is essential for pathogenicity and survival of bacterial pathogens in planta. X. fastidiosa, with a single MDR system, is significantly more vulnerable to inhibition by small-molecule treatments than most bacterial pathogens […]
Publications (2018-2020) Guanabenz acetate induces endoplasmic reticulum stress-related cell death in hepatocellular carcinoma cells
Kang, H. J. et al.
J. Pathol. Transl. Med. 53 94–103 (2019)
Background Development of chemotherapeutics for the treatment of advanced hepatocellular carcinoma (HCC) has been lagging. Screening of candidate therapeutic agents by using patient-derived preclinical models may facilitate drug discovery for HCC patients. Methods Four primary cultured HCC cells from surgically resected tumor tissues and six HCC cell lines were used for high-throughput screening of 252 […]
Publications (2018-2020) Screening and evaluation of antiviral compounds against Equid alpha-herpesviruses using an impedance-based cellular assay
Thieulent, C. J. et al.
Virology 526 105–116 (2019)
Equid alpha-herpesviruses (EHV) are responsible for different diseases in equine population. EHV-1 causes respiratory diseases, abortions and nervous disorders, EHV-4 causes respiratory diseases and sporadic abortion, while EHV-3 is responsible of equine coital exanthema. In view of the lack of efficacy of vaccines against EHV-1 and EHV-4 and in the absence of vaccines against EHV-3, the use […]
Publications (2018-2020) First-in-class allosteric inhibitors of bacterial IMPDHs
Alexandre, T. et al.
Eur. J. Med. Chem. 167 124–132 (2019)
Inosine-5′-monophosphate dehydrogenase (IMPDH) is an essential enzyme in many bacterial pathogens and is considered as a potential drug target for the development of new antibacterial agents. Our recent work has revealed the crucial role of one of the two structural domains (i.e. Bateman domain) in the regulation of the quaternary structure and enzymatic activity of […]
Publications (2018-2020) Metabolomics-Driven Exploration of the Chemical Drug Space to Predict Combination Antimicrobial Therapies
Campos, A. I. & Zampieri, M.
Mol. Cell 74 1291-1303.e6 (2019)
Alternative to the conventional search for single-target, single-compound treatments, combination therapies can open entirely new opportunities to fight antibiotic resistance. However, combinatorial complexity prohibits experimental testing of drug combinations on a large scale, and methods to rationally design combination therapies are lagging behind. Here, we developed a combined experimental-computational approach to predict drug-drug interactions using […]
Publications (2018-2020) Identification of Off-Patent Compounds That Present Antifungal Activity against the Emerging Fungal Pathogen Candida auris
De Oliveira, H. C. et al.
Front. Cell. Infect. Microbiol. 9 1–10 (2019)
Candida auris is an emerging fungal pathogen of great concern among the scientific community because it is causing an increasing number of hospital outbreaks of difficult management worldwide. In addition, isolates from this species frequently present reduced susceptibility to azole and echinocandin drugs. For this reason, it is necessary to develop new antifungal strategies to better […]
Publications (2018-2020) Evaluation of a library of FDA-approved drugs for their ability to potentiate antibiotics against multidrug-resistant gram-negative pathogens
Hind, C. K. et al.
Antimicrob. Agents Chemother. 63 1–6 (2019)
The Prestwick library was screened for antibacterial activity or « antibiotic resistance breaker » (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, and gemcitabine), anthracyclines (daunorubicin, mitoxantrone, and epirubicin), and psychoactive drugs (gabapentin, fluspirilene, and […]
Publications (2018-2020) Drug‐induced increase in lysobisphosphatidic acid reduces the cholesterol overload in Niemann–Pick type C cells and mice
Moreau, D. et al.
EMBO Rep. 20 1–15 (2019)
Most cells acquire cholesterol by endocytosis of circulating low‐density lipoproteins (LDLs). After cholesteryl ester de‐esterification in endosomes, free cholesterol is redistributed to intracellular membranes via unclear mechanisms. Our previous work suggested that the unconventional phospholipid lysobisphosphatidic acid (LBPA) may play a role in modulating the cholesterol flux through endosomes. In this study, we used the […]
Publications (2018-2020) Fibrates as drugs with senolytic and autophagic activity for osteoarthritis therapy
Nogueira-Recalde, U. et al.
EBioMedicine 45 588–605 (2019)
Background Ageing-related failure of homeostasis mechanisms contributes to articular cartilage degeneration and osteoarthritis (OA), for which disease-modifying treatments are not available. Our objective was to identify molecules to prevent OA by regulating chondrocyte senescence and autophagy. Methods Human chondrocytes with IL-6 induced senescence and autophagy suppression and SA-β-gal as a reporter of senescence and LC3 […]