{"id":1118606,"date":"2023-10-16T06:42:13","date_gmt":"2023-10-16T10:42:13","guid":{"rendered":"https:\/\/www.euvolution.com\/prometheism-transhumanism-posthumanism\/uncategorized\/unrealized-targets-in-the-discovery-of-antibiotics-for-gram-negative-nature-com\/"},"modified":"2023-10-16T06:42:13","modified_gmt":"2023-10-16T10:42:13","slug":"unrealized-targets-in-the-discovery-of-antibiotics-for-gram-negative-nature-com","status":"publish","type":"post","link":"https:\/\/www.euvolution.com\/prometheism-transhumanism-posthumanism\/transhuman-news-blog\/human-genetics\/unrealized-targets-in-the-discovery-of-antibiotics-for-gram-negative-nature-com\/","title":{"rendered":"Unrealized targets in the discovery of antibiotics for Gram-negative &#8230; &#8211; Nature.com"},"content":{"rendered":"<p><p>        Butler, M. S. et al. Analysis of the clinical pipeline of        treatments for drug-resistant bacterial infections: despite        progress, more action is needed. Antimicrob. Agents        Chemother. 66, e0199121 (2022).      <\/p>\n<p>        Article PubMed                Google Scholar      <\/p>\n<p>        Martnez-Garca, L., Gonzlez-Alba, J. M., Baquero, F.,        Cantn, R. & Galn, J. C. Ceftazidime is the key        diversification and selection driver of VIM-type        carbapenemases. mBio 9, e02109e02117 (2018).      <\/p>\n<p>        Article PubMed        PubMed        Central         Google Scholar      <\/p>\n<p>        Baquero, F. et al. Allogenous selection of mutational        collateral resistance: old drugs select for new resistance        within antibiotic families. Front. Microbiol.        12, 757833 (2021).      <\/p>\n<p>        Article        PubMed        PubMed        Central         Google Scholar      <\/p>\n<p>        Rajer, F., Allander, L., Karlsson, P. A. & Sandegren, L.        Evolutionary trajectories toward high-level        -lactam\/-lactamase inhibitor resistance in the presence        of multiple -lactamases. Antimicrob. Agents        Chemother. 66, e0029022 (2022).      <\/p>\n<p>        Article PubMed                Google Scholar      <\/p>\n<p>        Poirel, L., Sadek, M., Kusaksizoglu, A. & Nordmann, P.        Co-resistance to ceftazidimeavibactam and cefiderocol in        clinical isolates producing KPC variants. Eur. J. Clin.        Microbiol. Infect. Dis. 41, 677680 (2022).      <\/p>\n<p>        Article        CAS PubMed                Google Scholar      <\/p>\n<p>        Silver, L. L. Challenges of antibacterial discovery.        Clin. Microbiol. Rev. 24, 71109 (2011).      <\/p>\n<p>        Article CAS PubMed        PubMed        Central         Google Scholar      <\/p>\n<p>        Baker, S. J., Payne, D. J., Rappuoli, R. & De Gregorio, E.        Technologies to address antimicrobial resistance. Proc.        Natl Acad. Sci. USA 115, 1288712895 (2018).      <\/p>\n<p>        Article CAS PubMed        PubMed        Central         Google Scholar      <\/p>\n<p>        Payne, D. J., Gwynn, M. N., Holmes, D. J. & Pompliano, D.        L. Drugs for bad bugs: confronting the challenges of        antibacterial discovery. Nat. Rev. Drug Discov.        6, 2940 (2007).      <\/p>\n<p>        Article CAS PubMed                Google Scholar      <\/p>\n<p>        Tommasi, R., Brown, D. G., Walkup, G. K., Manchester, J. I.        & Miller, A. A. ESKAPEing the labyrinth of antibacterial        discovery. Nat. Rev. Drug Discov. 14, 529542        (2015).      <\/p>\n<p>        Article CAS PubMed                Google Scholar      <\/p>\n<p>        Brotz-Oesterhelt, H. & Sass, P. Postgenomic strategies in        antibacterial drug discovery. Future Microbiol.        5, 15531579 (2010).      <\/p>\n<p>        Article PubMed                Google Scholar      <\/p>\n<p>        Lewis, K. Platforms for antibiotic discovery. Nat. Rev.        Drug Discov. 12, 371387 (2013).      <\/p>\n<p>        Article CAS PubMed                Google Scholar      <\/p>\n<p>        Muoz, K. A. & Hergenrother, P. J. Facilitating compound        entry as a means to discover antibiotics for Gram-negative        bacteria. Acc. Chem. Res. 54, 13221333        (2021).      <\/p>\n<p>        Article        PubMed        PubMed        Central         Google Scholar      <\/p>\n<p>        Zhao, S. et al. Defining new chemical space for drug        penetration into Gram-negative bacteria. Nat. Chem.        Biol. 16, 12931302 (2020).      <\/p>\n<p>        Article        CAS PubMed        PubMed        Central         Google Scholar      <\/p>\n<p>        Sadybekov, A. V. & Katritch, V. Computational approaches        streamlining drug discovery. Nature 616,        673685 (2023).      <\/p>\n<p>        Article        CAS PubMed                Google Scholar      <\/p>\n<p>        Lluka, T. & Stokes, J. M. Antibiotic discovery in the        artificial intelligence era. Ann. NY Acad. Sci.        1519, 7493 (2023).      <\/p>\n<p>        Article CAS PubMed                Google Scholar      <\/p>\n<p>        Lyu, J. et al. Ultra-large library docking for discovering        new chemotypes. Nature 566, 224229 (2019).      <\/p>\n<p>        Article        CAS PubMed        PubMed        Central         Google Scholar      <\/p>\n<p>        Mobegi, F. M. et al. From microbial gene essentiality to        novel antimicrobial drug targets. BMC Genomics        15, 958 (2014).      <\/p>\n<p>        Article PubMed        PubMed        Central         Google Scholar      <\/p>\n<p>        Agarwal, P. & Searls, D. B. Can literature analysis        identify innovation drivers in drug discovery? Nat. Rev.        Drug Discov. 8, 865 (2009).      <\/p>\n<p>        Article CAS PubMed        PubMed        Central         Google Scholar      <\/p>\n<p>        Lange, R. P., Locher, H. H., Wyss, P. C. & Then, R. L. The        targets of currently used antibacterial agents: lessons for        drug discovery. Curr. Pharm. Des. 13,        31403154 (2007).      <\/p>\n<p>        Article        CAS PubMed                Google Scholar      <\/p>\n<p>        Theuretzbacher, U. & Piddock, L. J. V. Non-traditional        antibacterial therapeutic options and challenges. Cell        Host Microbe 26, 6172 (2019).      <\/p>\n<p>        Article        CAS PubMed                Google Scholar      <\/p>\n<p>        Frearson, J. A., Wyatt, P. G., Gilbert, I. H. & Fairlamb,        A. H. Target assessment for antiparasitic drug discovery.        Trends Parasitol. 23, 589595 (2007).      <\/p>\n<p>        Article CAS PubMed        PubMed        Central         Google Scholar      <\/p>\n<p>        Streker, K. et al. In vitro and in vivo validation of ligA        and tarI as essential targets in Staphylococcus        aureus. Antimicrob. Agents Chemother. 52,        44704474 (2008).      <\/p>\n<p>        Article CAS PubMed        PubMed        Central         Google Scholar      <\/p>\n<p>        Rancati, G., Moffat, J., Typas, A. & Pavelka, N. Emerging        and evolving concepts in gene essentiality. Nat. Rev.        Genet. 19, 3449 (2018).      <\/p>\n<p>        Article CAS PubMed                Google Scholar      <\/p>\n<p>        Bosch-Guiteras, N. & van Leeuwen, J. Exploring conditional        gene essentiality through systems genetics approaches in        yeast. Curr. Opin. Genet. Dev. 76, 101963        (2022).      <\/p>\n<p>        Article        CAS PubMed                Google Scholar      <\/p>\n<p>        Zhang, Z. & Ren, Q. Why are essential genes essential?         the essentiality of Saccharomyces genes. Microb.        Cell 2, 280287 (2015).      <\/p>\n<p>        Article CAS PubMed        PubMed        Central         Google Scholar      <\/p>\n<p>        Chessher, A. Evaluating the suitability of essential genes        as targets for antibiotic screening assays using        proteomics. Protein Cell 3, 57 (2012).      <\/p>\n<p>        Article        PubMed        PubMed        Central         Google Scholar      <\/p>\n<p>        Editorial. Putting gene essentiality into context. Nat.        Rev. Genet. 19, 1 (2017).      <\/p>\n<p>                Google Scholar      <\/p>\n<p>        Chaudhary, A. S., Chen, W., Jin, J., Tai, P. C. & Wang, B.        SecA: a potential antimicrobial target. Future Med.        Chem. 7, 9891007 (2015).      <\/p>\n<p>        Article CAS PubMed                Google Scholar      <\/p>\n<p>        Emmerich, C. H. et al. Improving target assessment in        biomedical research: the GOT-IT recommendations. Nat.        Rev. Drug Discov. 20, 6481 (2021).      <\/p>\n<p>        Article        CAS PubMed                Google Scholar      <\/p>\n<p>        Murima, P., McKinney, J. D. & Pethe, K. Targeting bacterial        central metabolism for drug development. Chem. Biol.        21, 14231432 (2014).      <\/p>\n<p>        Article        CAS PubMed                Google Scholar      <\/p>\n<p>        Hedstrom, L. The bare essentials of antibiotic target        validation. ACS Infect. Dis. 3, 24 (2017).      <\/p>\n<p>        Article        CAS PubMed                Google Scholar      <\/p>\n<p>        Hogan, A. M. & Cardona, S. T. Gradients in gene        essentiality reshape antibacterial research. FEMS        Microbiol. Rev. 46, fuac005 (2022).      <\/p>\n<p>        Article PubMed        PubMed        Central         Google Scholar      <\/p>\n<p>        Bergmiller, T., Ackermann, M. & Silander, O. K. Patterns of        evolutionary conservation of essential genes correlate with        their compensability. PLoS Genet. 8, e1002803        (2012).      <\/p>\n<p>        Article        CAS PubMed        PubMed        Central         Google Scholar      <\/p>\n<p>        Dunman, P. M. & Tomaras, A. P. Translational deficiencies        in antibacterial discovery and new screening paradigms.        Curr. Opin. Microbiol. 27, 108113 (2015).      <\/p>\n<p>        Article        CAS PubMed        PubMed        Central         Google Scholar      <\/p>\n<p>        Rosconi, F. et al. A bacterial pan-genome makes gene        essentiality strain-dependent and evolvable. Nat.        Microbiol. 7, 15801592 (2022).      <\/p>\n<p>        Article        CAS PubMed        PubMed        Central         Google Scholar      <\/p>\n<p>        Kaur, H., Kalia, M. & Taneja, N. Identification of novel        non-homologous drug targets against Acinetobacter        baumannii using subtractive genomics and comparative        metabolic pathway analysis. Microb. Pathog.        152, 104608 (2021).      <\/p>\n<p>        Article        CAS PubMed                Google Scholar      <\/p>\n<p>        Uddin, R., Masood, F., Azam, S. S. & Wadood, A.        Identification of putative non-host essential genes and        novel drug targets against Acinetobacter baumannii        by in silico comparative genome analysis. Microb.        Pathog. 128, 2835 (2019).      <\/p>\n<p>        Article        CAS PubMed                Google Scholar      <\/p>\n<p>        Ramos, P. I. P. et al. An integrative, multi-omics approach        towards the prioritization of Klebsiella pneumoniae        drug targets. Sci. Rep. 8, 10755 (2018).      <\/p>\n<p>        Article        PubMed        PubMed        Central         Google Scholar      <\/p>\n<p>        Rafiq, H. et al. A computational subtractive genome        analysis for the characterization of novel drug targets in        Klebsiella pneumoniae strain PittNDM01. Microb.        Pathog. 146, 104245 (2020).      <\/p>\n<p>        Article        CAS PubMed                Google Scholar      <\/p>\n<p>        Uddin, R. & Jamil, F. Prioritization of potential drug        targets against P. aeruginosa by core proteomic        analysis using computational subtractive genomics and        proteinprotein interaction network. Comput. Biol.        Chem. 74, 115122 (2018).      <\/p>\n<p>        Article        CAS PubMed                Google Scholar      <\/p>\n<p>        Nazarshodeh, E., Marashi, S. A. & Gharaghani, S. Structural        systems pharmacology: a framework for integrating metabolic        network and structure-based virtual screening for drug        discovery against bacteria. PLoS ONE 16,        e0261267 (2021).      <\/p>\n<p>        Article        CAS PubMed        PubMed        Central         Google Scholar      <\/p>\n<p>        Bakheet, T. M. & Doig, A. J. Properties and identification        of antibiotic drug targets. BMC Bioinformatics        11, 195 (2010).      <\/p>\n<p>        Article PubMed        PubMed        Central         Google Scholar      <\/p>\n<p>        Bosch, B. et al. Genome-wide gene expression tuning reveals        diverse vulnerabilities of M. tuberculosis.        Cell 184, 45794592.e24 (2021).      <\/p>\n<p>        Article        CAS PubMed        PubMed        Central         Google Scholar      <\/p>\n<p>        Hawkins, J. S. et al. Mismatch-CRISPRi reveals the        co-varying expressionfitness relationships of essential        genes in Escherichia coli and Bacillus        subtilis. Cell Syst. 11, 523535.e9        (2020).      <\/p>\n<p>        Article        CAS PubMed        PubMed        Central         Google Scholar      <\/p>\n<p>        Luo, H., Gao, F. & Lin, Y. Evolutionary conservation        analysis between the essential and nonessential genes in        bacterial genomes. Sci. Rep. 5, 13210 (2015).      <\/p>\n<p>        Article CAS PubMed        PubMed        Central         Google Scholar      <\/p>\n<p>        Arun, P. V. P. S. et al. Identification and functional        analysis of essential, conserved, housekeeping and        duplicated genes. FEBS Lett. 590, 14281437        (2016).      <\/p>\n<p>        Article CAS PubMed                Google Scholar      <\/p>\n<p>        Du, W. et al. Two active forms of        UDP-N-acetylglucosamine enolpyruvyl transferase in        Gram-positive bacteria. J. Bacteriol. 182,        41464152 (2000).      <\/p>\n<p>        Article        CAS PubMed        PubMed        Central         Google Scholar      <\/p>\n<p>        Naz, S., Ngo, T., Farooq, U. & Abagyan, R. Analysis of drug        binding pockets and repurposing opportunities for twelve        essential enzymes of ESKAPE pathogens. PeerJ        5, e3765e3765 (2017).      <\/p>\n<p>        Article PubMed        PubMed        Central         Google Scholar      <\/p>\n<p>        Klahn, P. & Bronstrup, M. New structural templates for        clinically validated and novel targets in antimicrobial        drug research and development. Curr. Top. Microbiol.        Immunol. 398, 365417 (2016).      <\/p>\n<p>        CAS PubMed                Google Scholar      <\/p>\n<p>        Miranda, R. R., Parthasarathy, A. & Hudson, A. O.        Exploration of chemical biology approaches to facilitate        the discovery and development of novel antibiotics.        Front. Trop. Dis. 3, 845469 (2022).      <\/p>\n<p>        Article         Google Scholar      <\/p>\n<p><!-- Auto Generated --><\/p>\n<p>See the original post:<br \/>\n<a target=\"_blank\" href=\"https:\/\/www.nature.com\/articles\/s41573-023-00791-6\" title=\"Unrealized targets in the discovery of antibiotics for Gram-negative ... - Nature.com\" rel=\"noopener\">Unrealized targets in the discovery of antibiotics for Gram-negative ... - Nature.com<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"<p> Butler, M. S. et al.  <a href=\"https:\/\/www.euvolution.com\/prometheism-transhumanism-posthumanism\/transhuman-news-blog\/human-genetics\/unrealized-targets-in-the-discovery-of-antibiotics-for-gram-negative-nature-com\/\">Continue reading <span class=\"meta-nav\">&rarr;<\/span><\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[27],"tags":[],"class_list":["post-1118606","post","type-post","status-publish","format-standard","hentry","category-human-genetics"],"_links":{"self":[{"href":"https:\/\/www.euvolution.com\/prometheism-transhumanism-posthumanism\/wp-json\/wp\/v2\/posts\/1118606"}],"collection":[{"href":"https:\/\/www.euvolution.com\/prometheism-transhumanism-posthumanism\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.euvolution.com\/prometheism-transhumanism-posthumanism\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.euvolution.com\/prometheism-transhumanism-posthumanism\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.euvolution.com\/prometheism-transhumanism-posthumanism\/wp-json\/wp\/v2\/comments?post=1118606"}],"version-history":[{"count":0,"href":"https:\/\/www.euvolution.com\/prometheism-transhumanism-posthumanism\/wp-json\/wp\/v2\/posts\/1118606\/revisions"}],"wp:attachment":[{"href":"https:\/\/www.euvolution.com\/prometheism-transhumanism-posthumanism\/wp-json\/wp\/v2\/media?parent=1118606"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.euvolution.com\/prometheism-transhumanism-posthumanism\/wp-json\/wp\/v2\/categories?post=1118606"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.euvolution.com\/prometheism-transhumanism-posthumanism\/wp-json\/wp\/v2\/tags?post=1118606"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}