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• W2026064133 abstract "Future MicrobiologyVol. 6, No. 6 Special Focus Issue: Antimicrobial Drug Discovery - ForewordFree AccessAntimicrobial drug discoveryAlan Fairlamb & Stewart ColeAlan Fairlamb† Author for correspondenceWellcome Principal Research Fellow, Division of Biological Chemistry & Drug Discovery, School of Life Sciences, Wellcome Trust Biocentre, University of Dundee, Dundee DD1 5EH, Scotland, UK. Search for more papers by this authorEmail the corresponding author at a.h.fairlamb@dundee.ac.uk & Stewart ColeGlobal Health Institute, Ecole Polytechnique Fédérale de Lausanne (EPFL), Station 19, CH-1015, Lausanne, SwitzerlandSearch for more papers by this authorPublished Online:27 Jun 2011https://doi.org/10.2217/fmb.11.54AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinkedInRedditEmail Novel antibiotics are urgently required to combat the relentless rise in antimicrobial drug resistance, and affordable new drugs with improved efficacy and a better safety profile are required for many neglected tropical diseases. New drugs are also needed for orphan diseases, for example Pseudomonas aeruginosa infections in cystic fibrosis, or hospital-acquired infections, such as Clostridium difficile-associated diarrhea, where narrow spectrum antibiotics may play an important clinical role. In addition, the potential use of biological agents for terrorist purposes remains a constant threat around the world. It is against this background of the continuing battle between humanity and infectious diseases that this special focus issue of Future Microbiology is set.While it is not possible to cover every aspect of antimicrobial drug development in a single special focus issue, the Commissioning Editors are confident that there is something of interest for everyone in these editorial and review articles. The principles underlying the discovery and development of small molecule drugs to combat infectious disease are broadly similar; only the desired therapeutic profile of the final product differs (e.g., narrow- vs broad-spectrum activity; static vs cidal; oral vs parenteral administration; target tissues).Two thoughtful editorials raise challenging issues for further debate. Martínez et al. discuss whether nonlethal targets could be useful as antimicrobials in certain diseases [1], whereas Dick and Young provocatively challenge the fashionable target-based approach to drug discovery without due consideration of the downstream consequences of target inhibition that could trigger ‘cell death pathways’ [2]. Regarding antibiotic kill rates, Mouton [3] evaluates a priority paper by Tam and Nikolaou [4] describing a novel computational approach to pharmacodynamic assessment of antimicrobial agents. This approach could be used to design optimal dosing regimens and prolong the clinical utility of novel antibiotics.The review by Sala and Hartkoorn provides a thoughtful and balanced discussion of the strengths and weaknesses of target-based versus phenotypic (whole cell) screening approaches to drug discovery [5]. Although focused on TB, the principles outlined in their review are equally applicable to other bacterial, malarial, trypanosomal or fungal infections.Not all antimicrobial drug targets can be readily identified from mining of genomic databases. Membrane targeting drugs, such as the peptide antibiotic, daptomycin, and the natural product, amphotericin, are interesting exemplars. In a comprehensive review, Eckert considers the important challenges facing the development of antimicrobial peptide antibiotics, such as mode of delivery, cost of goods and regulatory issues, and presents novel strategies to address these important questions [6]. In the special case of bioterrorism agents (some of which are also neglected tropical diseases), Sarkar-Tyson and Atkins review currently available therapies against various bacterial pathogens and discuss novel strategies for targeting bacterial virulence factors [7]. The authors propose that inhibition of the type III secretion systems involved in release of effector proteins required for host-cell invasion could represent novel therapeutic targets against these pathogens.The emergence and worldwide spread of antibiotic resistance to carbapenems in Enterobacteriaciae is considered a potential nightmare scenario. Falagas et al. survey the rather meagre therapeutic alternatives [8]. These authors propose that combination antimicrobial therapy might fill the gap until much needed novel classes of antibiotics are developed. In the case of malaria, artemisinin combination therapy is standard WHO policy aimed at slowing the emergence of resistance to the partner drugs. The recent reports of the emergence of partial artemisinin-resistant Plasmodium falciparum malaria on the Cambodia–Thailand border threaten to undermine this policy. McNamara and Winzeler review the current status of antimalarial chemotherapy and discuss strategies such as ‘genome scanning’ to identify the targets of several novel compound classes, discovered by phenotypic screening of nearly 5 million compounds, which could potentially replace artemisinin in combination therapy [9]. Drug treatment for human African trypanosomiasis is unsatisfactory, particularly when the CNS has been infected, and a replacement for the organo-arsenical drug melarsoprol that kills 1 in 20 patients who receive it is urgently required. As reviewed by Brun et al., two promising drug candidates, fexinidazole and the oxaborole SCYX-7158, are in the early stages of clinical development under the auspices of the Drugs for Neglected Diseases initiative [10].In conclusion, this special focus issue highlights some of the pitfalls of drug discovery and offers novel strategies to accelerate drug discovery. The increasing collaborative efforts of academia and the pharmaceutical industry with funding from governments, product development partnerships and charities hold great promise in accelerating the discovery and development of new treatments for infectious diseases.Financial & competing interests disclosureA Fairlamb is in receipt of a Principal Research Fellowship and program funding from the Wellcome Trust. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.No writing assistance was utilized in the production of this manuscript.Bibliography1 Martínez JL, Rojo F, Vila J: Are nonlethal targets useful for developing novel antimicrobials? Future Microbiol.6(6),605–607 (2011).Link, Google Scholar2 Dick T, Young D: How antibacterials really work: impact on drug discovery. Future Microbiol.6(6),603–604 (2011).Link, Google Scholar3 Mouton JW: Relationship between pharmacodynamic indices and killing patterns in vitro. Future Microbiol.6(6),613–616 (2011).Link, CAS, Google Scholar4 Tam VH, Nikolaou M: A novel approach to pharmacodynamic assessment of antimicrobial agents: new insights to dosing regimen design. PLoS Comput. Biol.7(1),E1001043 (2011).Crossref, Medline, CAS, Google Scholar5 Sala C, Hartkoorn RC: Tuberculosis drugs: new candidates and how to find more. Future Microbiol.6(6),617–633 (2011).Link, Google Scholar6 Eckert R: Road to clinical efficacy: challenges and novel strategies for antimicrobial peptide development. Future Microbiol.6(6),635–651 (2011).Link, CAS, Google Scholar7 Sarkar-Tyson M, Atkins HS: Antimicrobials for bacterial bioterrorism agents. Future Microbiol.6(6),667–676 (2011).Link, CAS, Google Scholar8 Falagas ME, Karageorgopoulos DE, Nordmann P: Therapeutic options for infections with Enterobacteriaceae producing carbapenem-hydrolyzing enzymes. Future Microbiol.6(6),653–666 (2011).Link, CAS, Google Scholar9 McNamara C, Winzeler EA: Target identification and validation of novel antimalarials. Future Microbiol.6(6),693–704 (2011).Link, CAS, Google Scholar10 Brun R, Don R, Jacobs RT, Wang MZ, Barrett MP: Development of novel drugs for human African trypanosomiasis. Future Microbiol.6(6),677–691 (2011).Link, CAS, Google ScholarFiguresReferencesRelatedDetailsCited ByFabrication of polycaprolactone nanofibrous membrane‐embedded microfluidic device for water filtration13 March 2020 | Journal of Applied Polymer Science, Vol. 137, No. 40Antimicrobial effect of polydopamine coating on Escherichia coliJournal of Materials Chemistry, Vol. 22, No. 40 Vol. 6, No. 6 Follow us on social media for the latest updates Metrics History Published online 27 June 2011 Published in print June 2011 Information© Future Medicine LtdFinancial & competing interests disclosureA Fairlamb is in receipt of a Principal Research Fellowship and program funding from the Wellcome Trust. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.No writing assistance was utilized in the production of this manuscript.PDF download" @default.
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