Contribution of high‐content imaging technologies to the development of anti‐infective drugs

Ang, Michelle; Pethe, Kévin

doi:10.1002/cyto.a.22885

Cited by 16 publications

(16 citation statements)

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“…Depending on the global distribution of the target of interest, these efforts aid, in particular,i nt he identification of potent antibiotic and antivirulence (see also Section 4) candidates which spare commensal bacteria and are likely less toxic to eukaryotic cells. [101][102][103][104] Additionally,c omputational methods have been av ery valuable tool for the screening and analysis of potential antibiotics.T he substantial advances in the "-omics" fields including genomics,p roteomics,a nd metabolomics have resulted in av eritable explosion of (phenotypic) data. [88] Reporter strains are genetically engineered bacterial strains that allow the readout of aspecific physiological perturbation by the altered expression of ar eporter gene,s uch as GFP.…”

Section: Screening Platformsmentioning

confidence: 99%

“…In particular,t he automation of microscopic imaging nowadays allows not only the parallel monitoring of various cellular characteristics and functions in bacterial cells,but also cellular bacterial infection models.B CP can not only be applied to phenotypic drug discovery screening,b ut also to cytological profiling experiments that allow the study of adrugsmode of action. [101][102][103][104] Additionally,c omputational methods have been av ery valuable tool for the screening and analysis of potential antibiotics.T he substantial advances in the "-omics" fields including genomics,p roteomics,a nd metabolomics have resulted in av eritable explosion of (phenotypic) data. Bioinformatic approaches aim to take advantage of these huge data sets to identify new antibacterial compounds and potential new targets or to help clarify the mode of action of new compounds.…”

Section: Screening Platformsmentioning

confidence: 99%

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Thinking Outside the Box—Novel Antibacterials To Tackle the Resistance Crisis

et al. 2018

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The public view on antibiotics as reliable medicines changed when reports about "resistant superbugs" appeared in the news. While reasons for this resistance development are easily spotted, solutions for re-establishing effective antibiotics are still in their infancy. This Review encompasses several aspects of the antibiotic development pipeline from very early strategies to mature drugs. An interdisciplinary overview is given of methods suitable for mining novel antibiotics and strategies discussed to unravel their modes of action. Select examples of antibiotics recently identified by using these platforms not only illustrate the efficiency of these measures, but also highlight promising clinical candidates with therapeutic potential. Furthermore, the concept of molecules that disarm pathogens by addressing gatekeepers of virulence will be covered. The Review concludes with an evaluation of antibacterials currently in clinical development. Overall, this Review aims to connect select innovative antimicrobial approaches to stimulate interdisciplinary partnerships between chemists from academia and industry.

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Section: Screening Platformsmentioning

confidence: 99%

Section: Screening Platformsmentioning

confidence: 99%

Thinking Outside the Box—Novel Antibacterials To Tackle the Resistance Crisis

et al. 2018

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“…[101][102][103][104] Zusätzlich sind computerbasierte Te chniken sehr wertvoll fürdas Screening und die Analyse von potentiellen Antibiotika. Insbesondere die Automatisierung der mikroskopischen Bildgebung erlaubt heute nicht nur die parallele Beobachtung verschiedener zellulärer Charakteristika und Funktionen in Bakterien, sondern auch in Infektionsmodellen.…”

Section: Screening-plattformenunclassified

“…Um den unterschiedlichen physiologischen Parametern, wie der Zellwandstruktur oder dem Virulenzmechanismus,v erschiedener bakterieller Stämme gerecht zu werden, kçnnen reporterbasierte Assays direkt im gewünschten Bakterium durchgeführt werden. Screenings in wildtypischen oder multiresistenten Bakterien wurden beispielsweise in S. aureus, [95,96] V. cholerae, [97] K. pneumoniae [98] und P. aeruginosa [99,100] [101][102][103][104] Zusätzlich sind computerbasierte Te chniken sehr wertvoll fürdas Screening und die Analyse von potentiellen Antibiotika. Die wesentlichen Fortschritte in den "-omik"-Feldern wie Genomik, Proteomik oder Metabolomik haben zu einer regelrechten Explosion von (phänotypischen) Daten geführt.…”

Section: Screening-plattformenunclassified

Über bisherige Denkweisen hinaus – neue Wirkstoffe zur Überwindung der Antibiotika‐Krise

et al. 2018

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Die öffentliche Wahrnehmung von Antibiotika als verlässliche Arzneimittel veränderte sich drastisch, als Meldungen über “multiresistente Super‐Erreger” die Nachrichten aufrüttelten. Während die Ursachen für die bakterielle Resistenzentwicklung schnell erkannt wurden, befindet sich die Forschung zur Wiedergewinnung von Antibiotika als effektive Arzneistoffe immer noch am Anfang. Dieser Aufsatz umfasst zahlreiche Aspekte des Entwicklungsprozesses neuer Antibiotika, von der Grundlagenforschung bis zum fertigen Medikament. Er bietet einen interdisziplinären Überblick über Methoden zur Identifizierung neuer Antibiotika und erörtert Strategien, um ihren molekularen Wirkmechanismus aufzuklären. Die Darstellung ausgewählter Antibiotika, die kürzlich mithilfe dieser Plattformen entdeckt wurden, verdeutlicht die Effizienz der Ansätze und hebt vielversprechende klinische Kandidaten mit therapeutischem Potential hervor. Zusätzlich wird das Konzept von Molekülen erörtert, die Krankheitserreger “entwaffnen”, indem sie Schlüsselpunkte der Virulenz adressieren. Der Aufsatz schließt mit einer kritischen Beurteilung jener antibakteriellen Wirkstoffe, die sich derzeit in klinischer Entwicklung befinden. Insgesamt soll dieser Aufsatz ausgewählte, innovative antibakterielle Ansätze verknüpfen, um interdisziplinäre Partnerschaften zwischen Chemikern aus der akademischen und industriellen Forschung anzuregen.

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“…In the first part of this special issue we highlight the continuous advancements improving performance for high‐content (HC) and high‐throughput (HT) imaging for a variety of applications from basic to applied and clinical research , in terms of [i] Reagents and assay tools , [ii] Microscopy advancements , [iii] Automation and robotics and [iv] Computational advancements . Whilst the performance in terms of speed is key for HT imaging, the image quality in terms of both resolution and signal:noise ratio (A.K.A.…”

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confidence: 99%

Pushing the boundaries of high content imaging

et al. 2017

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MICROSCOPY performance is routinely assessed based on three criteria (i) Speed, (ii) Resolution, and (iii) Sensitivity. Whilst we, the research community, have access to a spectacular array of advanced equipment, alas the perfect instrument does not exist-we cannot simultaneously have optimal performance in each criterion. For this reason, the ubiquitous triangle of compromise ( Fig. 1) is drawn to demonstrate these limitations. Thankfully, the triangle is continuously shrinking with new technological improvements.There are additional important considerations, like the need keep cells healthy in live-cell imaging experiments; ensuring the phenomenon being observed is not simply a consequence of phototoxicity; or how effective a given technique is in terms of depth-penetration into a 3D sample.Great technological strides have been made in improving instrument performance, but when one criteria is improved it often comes at a cost to another. For example, super resolution microscopy (1) allows us to surpass the diffraction barrier that otherwise limits the resolution (to $250 nm in the lateral, xy, direction), however these techniques are generally slow and less cell-friendly relative to more conventional approaches.In the first part of this special issue (2) we highlight the continuous advancements improving performance for highcontent (HC) and high-throughput (HT) imaging for a variety of applications from basic to applied and clinical research (3), in terms of [i] Reagents and assay tools (4-6), [ii] Microscopy advancements (6,7), [iii] Automation and robotics (7) and [iv] Computational advancements (8,9). Whilst the performance in terms of speed is key for HT imaging, the image quality in terms of both resolution and signal:noise ratio (A.K.A. sensitivity) is critical for HC imaging. The ideal HC instrument requires all three criteria to be enhanced. We want it all and we want it now! As will be clear from Part 2 of the special issue on High Throughput and High Content Imaging and Cellular Informatics, newer demands on HC imaging for live-cells, 3D samples, and whole organisms are becoming increasingly prevalent. This will provide the impetus for continued technological Figure 1. The triangle of compromise of microscopy performance.

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Contribution of high‐content imaging technologies to the development of anti‐infective drugs

Cited by 16 publications

References 50 publications

Thinking Outside the Box—Novel Antibacterials To Tackle the Resistance Crisis

Thinking Outside the Box—Novel Antibacterials To Tackle the Resistance Crisis

Über bisherige Denkweisen hinaus – neue Wirkstoffe zur Überwindung der Antibiotika‐Krise

Pushing the boundaries of high content imaging

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