{"id":1127530,"date":"2024-07-27T20:04:09","date_gmt":"2024-07-28T00:04:09","guid":{"rendered":"https:\/\/www.euvolution.com\/prometheism-transhumanism-posthumanism\/uncategorized\/macrolones-target-bacterial-ribosomes-and-dna-gyrase-and-can-evade-resistance-mechanisms-nature-com\/"},"modified":"2024-07-27T20:04:09","modified_gmt":"2024-07-28T00:04:09","slug":"macrolones-target-bacterial-ribosomes-and-dna-gyrase-and-can-evade-resistance-mechanisms-nature-com","status":"publish","type":"post","link":"https:\/\/www.euvolution.com\/prometheism-transhumanism-posthumanism\/transhuman-news-blog\/dna\/macrolones-target-bacterial-ribosomes-and-dna-gyrase-and-can-evade-resistance-mechanisms-nature-com\/","title":{"rendered":"Macrolones target bacterial ribosomes and DNA gyrase and can evade resistance mechanisms &#8211; Nature.com"},"content":{"rendered":"<p><p>        Fernandes, P. Use of antibiotic core structures to generate        new and useful macrolide antibiotics. In Antibiotics        Current Innovations and Future Trends (eds Snchez, S.        & Demain, A. L.) (Caister Academic Press, 2015).      <\/p>\n<p>        Bush, N. G., Diez-Santos, I., Abbott, L. R. & Maxwell, A.        Quinolones: mechanism, lethality and their contributions to        antibiotic resistance. Molecules 25, 5662        (2020).      <\/p>\n<p>        Article        CAS PubMed        PubMed        Central         Google Scholar      <\/p>\n<p>        Agouridas, C. et al. Synthesis and antibacterial activity        of ketolides (6-O-methyl-3-oxoerythromycin        derivatives): a new class of antibacterials highly potent        against macrolide-resistant and -susceptible respiratory        pathogens. J. Med. Chem. 41, 40804100        (1998).      <\/p>\n<p>        Article CAS PubMed                Google Scholar      <\/p>\n<p>        Seiple, I. B. et al. A platform for the discovery of new        macrolide antibiotics. Nature 533, 338345        (2016).      <\/p>\n<p>        Article CAS PubMed        PubMed        Central         Google Scholar      <\/p>\n<p>        Pavlovic, D., Fajdetic, A. & Mutak, S. Novel hybrids of        15-membered 8a- and 9a-azahomoerythromycin A ketolides and        quinolones as potent antibacterials. Bioorg. Med.        Chem. 18, 85668582 (2010).      <\/p>\n<p>        Article        CAS PubMed                Google Scholar      <\/p>\n<p>        Fan, B. Z. et al. Design, synthesis and structureactivity        relationships of novel 15-membered macrolides:        quinolone\/quinoline-containing sidechains tethered to the        C-6 position of azithromycin acylides. Eur. J. Med.        Chem. 193, 112222 (2020).      <\/p>\n<p>        Article        CAS PubMed                Google Scholar      <\/p>\n<p>        Barry, A. L. & Jones, R. N. Comparative in vitro activity        of amifloxacin and five other fluoroquinolone antimicrobial        agents and preliminary criteria for the disk susceptibility        test. Eur. J. Clin. Microbiol. 6, 179182        (1987).      <\/p>\n<p>        Article CAS PubMed                Google Scholar      <\/p>\n<p>        Yourassowsky, E., Van der Linden, M. P., Crokaert, F. &        Glupczynski, Y. In vitro activity of pefloxacin compared to        other antibiotics. J. Antimicrob. Chemother.        17, 1928 (1986).      <\/p>\n<p>        Article        CAS PubMed                Google Scholar      <\/p>\n<p>        Dinos, G. P. The macrolide antibiotic renaissance. Br.        J. Pharmacol. 174, 29672983 (2017).      <\/p>\n<p>        Article CAS PubMed        PubMed        Central         Google Scholar      <\/p>\n<p>        Vazquez-Laslop, N. & Mankin, A. S. How macrolide        antibiotics work. Trends Biochem. Sci. 43,        668684 (2018).      <\/p>\n<p>        Article        CAS PubMed        PubMed        Central         Google Scholar      <\/p>\n<p>        Lin, J., Zhou, D., Steitz, T. A., Polikanov, Y. S. &        Gagnon, M. G. Ribosome-targeting antibiotics: modes of        action, mechanisms of resistance, and implications for drug        design. Annu. Rev. Biochem. 87, 451478        (2018).      <\/p>\n<p>        Article        CAS PubMed        PubMed        Central         Google Scholar      <\/p>\n<p>        Schlunzen, F. et al. Structural basis for the antibiotic        activity of ketolides and azalides. Structure        11, 329338 (2003).      <\/p>\n<p>        Article        CAS PubMed                Google Scholar      <\/p>\n<p>        Dunkle, J. A., Xiong, L., Mankin, A. S. & Cate, J. H.        Structures of the Escherichia coli ribosome with        antibiotics bound near the peptidyl transferase center        explain spectra of drug action. Proc. Natl Acad. Sci.        USA 107, 1715217157 (2010).      <\/p>\n<p>        Article CAS PubMed        PubMed        Central         Google Scholar      <\/p>\n<p>        Bulkley, D., Innis, C. A., Blaha, G. & Steitz, T. A.        Revisiting the structures of several antibiotics bound to        the bacterial ribosome. Proc. Natl Acad. Sci. USA        107, 1715817163 (2010).      <\/p>\n<p>        Article CAS PubMed        PubMed        Central         Google Scholar      <\/p>\n<p>        Svetlov, M. S. et al. Structure of Erm-modified 70S        ribosome reveals the mechanism of macrolide resistance.        Nat. Chem. Biol. 17, 412420 (2021).      <\/p>\n<p>        Article        CAS PubMed        PubMed        Central         Google Scholar      <\/p>\n<p>        Beckert, B. et al. Structural and mechanistic basis for        translation inhibition by macrolide and ketolide        antibiotics. Nat. Commun. 12, 4466 (2021).      <\/p>\n<p>        Article        CAS PubMed        PubMed        Central         Google Scholar      <\/p>\n<p>        Tu, D., Blaha, G., Moore, P. B. & Steitz, T. A. Structures        of MLSBK antibiotics bound to mutated large ribosomal        subunits provide a structural explanation for resistance.        Cell 121, 257270 (2005).      <\/p>\n<p>        Article        CAS PubMed                Google Scholar      <\/p>\n<p>        Hansen, J. L. et al. The structures of four macrolide        antibiotics bound to the large ribosomal subunit. Mol.        Cell 10, 117128 (2002).      <\/p>\n<p>        Article        CAS PubMed                Google Scholar      <\/p>\n<p>        Svetlov, M. S. et al. High-resolution crystal structures of        ribosome-bound chloramphenicol and erythromycin provide the        ultimate basis for their competition. RNA 25,        600606 (2019).      <\/p>\n<p>        Article CAS PubMed        PubMed        Central         Google Scholar      <\/p>\n<p>        Chen, C. W. et al. Structural insights into the mechanism        of overcoming Erm-mediated resistance by macrolides acting        together with hygromycin-A. Nat. Commun. 14,        4196 (2023).      <\/p>\n<p>        Article        CAS PubMed        PubMed        Central         Google Scholar      <\/p>\n<p>        Jenni, S. & Ban, N. The chemistry of protein synthesis and        voyage through the ribosomal tunnel. Curr. Opin. Struct.        Biol. 13, 212219 (2003).      <\/p>\n<p>        Article        CAS PubMed                Google Scholar      <\/p>\n<p>        Kannan, K., Vzquez-Laslop, N. & Mankin, A. S. Selective        protein synthesis by ribosomes with a drug-obstructed exit        tunnel. Cell 151, 508520 (2012).      <\/p>\n<p>        Article        CAS PubMed                Google Scholar      <\/p>\n<p>        Davis, A. R., Gohara, D. W. & Yap, M. N. Sequence        selectivity of macrolide-induced translational attenuation.        Proc. Natl Acad. Sci. USA 111, 1537915384        (2014).      <\/p>\n<p>        Article CAS PubMed        PubMed        Central         Google Scholar      <\/p>\n<p>        Kannan, K. et al. The general mode of translation        inhibition by macrolide antibiotics. Proc. Natl Acad.        Sci. USA 111, 1595815963 (2014).      <\/p>\n<p>        Article CAS PubMed        PubMed        Central         Google Scholar      <\/p>\n<p>        Sothiselvam, S. et al. Binding of macrolide antibiotics        leads to ribosomal selection against specific substrates        based on their charge and size. Cell Rep. 16,        17891799 (2016).      <\/p>\n<p>        Article        CAS PubMed        PubMed        Central         Google Scholar      <\/p>\n<p>        Almutairi, M. M. et al. Co-produced natural ketolides        methymycin and pikromycin inhibit bacterial growth by        preventing synthesis of a limited number of proteins.        Nucleic Acids Res. 45, 95739582 (2017).      <\/p>\n<p>        Article CAS PubMed        PubMed        Central         Google Scholar      <\/p>\n<p>        Franceschi, F., Kanyo, Z., Sherer, E. C. & Sutcliffe, J.        Macrolide resistance from the ribosome perspective.        Curr. Drug Targets Infect. Disord. 4, 177191        (2004).      <\/p>\n<p>        Article CAS PubMed                Google Scholar      <\/p>\n<p>        Versalovic, J. et al. Mutations in 23S rRNA are associated        with clarithromycin resistance in Helicobacter        pylori. Antimicrob. Agents Chemother. 40,        477480 (1996).      <\/p>\n<p>        Article CAS PubMed        PubMed        Central         Google Scholar      <\/p>\n<p>        Wand, G. & Taylor, D. E. Site-specific mutations in the 23S        rRNA gene of Helicobacter pylori confer two types of        resistance to macrolide-lincosamide-streptogramin B        antibiotics. Antimicrob. Agents Chemother.        42, 19521958 (1998).      <\/p>\n<p>        Article         Google Scholar      <\/p>\n<p>        Shallom, S. J. & Zelazny, A. M. Detection of mixed        populations of clarithromycin-susceptible and -resistant        Mycobacterium abscessus strains. J. Clin.        Microbiol. 60, e0169421 (2022).      <\/p>\n<p>        Article PubMed                Google Scholar      <\/p>\n<p>        McGuire, J. M. et al. Ilotycin, a new antibiotic.        Antibiot. Chemother. (Northfield) 2, 281283        (1952).      <\/p>\n<p>        CAS PubMed                Google Scholar      <\/p>\n<p>        Kirst, H. A. Introduction to the macrolide antibiotics. In        Macrolide Antibiotics (eds Schnfeld, W. & Kirst, H.        A.) (Birkhuser Verlag, 2002).      <\/p>\n<p>        Iacoviello, V. R. & Zinner, S. H. Macrolides: a clinical        overview. In Macrolide Antibiotics (eds Parnham, M.        J. & Bruinvels, J.) (Birkhuser Verlag, 2002).      <\/p>\n<p>        Tanikawa, T. et al. Synthesis and antibacterial activity of        acylides (3-O-acyl-erythromycin derivatives): a        novel class of macrolide antibiotics. J. Med. Chem.        44, 40274030 (2001).      <\/p>\n<p>        Article CAS PubMed                Google Scholar      <\/p>\n<p>        Liang, J. H. et al. Structureactivity relationships of        novel alkylides: 3-O-arylalkyl clarithromycin        derivatives with improved antibacterial activities. Eur.        J. Med. Chem. 49, 289303 (2012).      <\/p>\n<p>        Article        CAS PubMed                Google Scholar      <\/p>\n<p>        Magee, T. V. et al. Novel 3-O-carbamoyl erythromycin        A derivatives (carbamolides) with activity against        resistant staphylococcal and streptococcal isolates.        Bioorg. Med. Chem. Lett. 23, 17271731        (2013).      <\/p>\n<p>        Article        CAS PubMed                Google Scholar      <\/p>\n<p>        Tang, D. et al. Design, synthesis, and antibacterial        activities of novel 3,6-bicyclolide oximes: length        optimization and zero carbon linker oximes. Bioorg. Med.        Chem. Lett. 18, 50785082 (2008).      <\/p>\n<p>        Article        CAS PubMed                Google Scholar      <\/p>\n<p>        Bryskier, A. & Denis, A. Ketolides: novel antibacterial        agents designed to overcome resistance to erythromycin A        within Gram-positive cocci. In Macrolide Antibiotics        (eds Schnfeld, W. & Kirst, H. A.) (Birkhuser Verlag,        2002).      <\/p>\n<p>        Fernandes, P., Martens, E., Bertrand, D. & Pereira, D. The        solithromycin journeyit is all in the chemistry.        Bioorg. Med. Chem. 24, 64206428 (2016).      <\/p>\n<p>        Article        CAS PubMed                Google Scholar      <\/p>\n<p>        Capobianco, J. O. et al. Studies of the novel ketolide        ABT-773: transport, binding to ribosomes, and inhibition of        protein synthesis in Streptococcus pneumoniae.        Antimicrob. Agents Chemother. 44, 15621567        (2000).      <\/p>\n<p>        Article        CAS PubMed        PubMed        Central         Google Scholar      <\/p>\n<p>        Llano-Sotelo, B. et al. Binding and action of CEM-101, a        new fluoroketolide antibiotic that inhibits protein        synthesis. Antimicrob. Agents Chemother. 54,        49614970 (2010).      <\/p>\n<p>        Article CAS PubMed        PubMed        Central         Google Scholar      <\/p>\n<p>        Douthwaite, S. Structureactivity relationships of        ketolides vs. macrolides. Clin. Microbiol. Infect.        7, 1117 (2001).      <\/p>\n<p>        Article        CAS PubMed                Google Scholar      <\/p>\n<p>        Svetlov, M. S., Cohen, S., Alsuhebany, N., Vazquez-Laslop,        N. & Mankin, A. S. A long-distance rRNA base pair impacts        the ability of macrolide antibiotics to kill bacteria.        Proc. Natl Acad. Sci. USA 117, 19711975        (2020).      <\/p>\n<p>        Article CAS PubMed        PubMed        Central         Google Scholar      <\/p>\n<p>        Ma, C. X. et al. Design, synthesis and structureactivity        relationships of novel macrolones: hybrids of 2-fluoro        9-oxime ketolides and carbamoyl quinolones with highly        improved activity against resistant pathogens. Eur. J.        Med. Chem. 169, 120 (2019).      <\/p>\n<p>        Article        PubMed                Google Scholar      <\/p>\n<p>        Liu, X. P. et al. Design and synthesis of novel macrolones        bridged with linkers from 11,12-positions of macrolides.        Bioorg. Med. Chem. Lett. 68, 128761 (2022).      <\/p>\n<p>        Article        CAS PubMed                Google Scholar      <\/p>\n<p>        Hutinec, A. et al. Novel        8a-aza-8a-homoerythromycin4-(3-substituted-amino)propionates        with broad spectrum antibacterial activity. Bioorg. Med.        Chem. Lett. 20, 32443249 (2010).      <\/p>\n<p>        Article        CAS PubMed                Google Scholar      <\/p>\n<p>        Drlica, K., Malik, M., Kerns, R. J. & Zhao, X.        Quinolone-mediated bacterial death. Antimicrob. Agents        Chemother. 52, 385392 (2008).      <\/p>\n<p>        Article CAS PubMed                Google Scholar      <\/p>\n<p>        Aldred, K. J., Kerns, R. J. & Osheroff, N. Mechanism of        quinolone action and resistance. Biochemistry        53, 15651574 (2014).      <\/p>\n<p>        Article CAS PubMed                Google Scholar      <\/p>\n<p>        Miotto, P., Cirillo, D. M. & Migliori, G. B. Drug        resistance in Mycobacterium tuberculosis: molecular        mechanisms challenging fluoroquinolones and pyrazinamide        effectiveness. Chest 147, 11351143 (2015).      <\/p>\n<p>        Article PubMed                Google Scholar      <\/p>\n<p>        Machalek, D. A. et al. Prevalence of mutations associated        with resistance to macrolides and fluoroquinolones in        Mycoplasma genitalium: a systematic review and        meta-analysis. Lancet Infect. Dis. 20,        13021314 (2020).      <\/p>\n<p>        Article        CAS PubMed                Google Scholar      <\/p>\n<p>        Lungu, I. A., Moldovan, O. L., Biris, V. & Rusu, A.        Fluoroquinolones hybrid molecules as promising        antibacterial agents in the fight against antibacterial        resistance. Pharmaceutics 14, 1749 (2022).      <\/p>\n<p>        Article        CAS PubMed        PubMed        Central         Google Scholar      <\/p>\n<p>        Pavlovic, D. & Mutak, S. Discovery of 4-ether linked        azithromycinquinolone hybrid series: influence of the        central linker on the antibacterial activity. ACS Med.        Chem. Lett. 2, 331336 (2011).      <\/p>\n<p>        Article CAS PubMed        PubMed        Central         Google Scholar      <\/p>\n<p><!-- Auto Generated --><\/p>\n<p>View post:<br \/>\n<a target=\"_blank\" href=\"https:\/\/www.nature.com\/articles\/s41589-024-01685-3\" title=\"Macrolones target bacterial ribosomes and DNA gyrase and can evade resistance mechanisms - Nature.com\" rel=\"noopener\">Macrolones target bacterial ribosomes and DNA gyrase and can evade resistance mechanisms - Nature.com<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"<p> Fernandes, P. Use of antibiotic core structures to generate new and useful macrolide antibiotics. In Antibiotics Current Innovations and Future Trends (eds Snchez, S.  <a href=\"https:\/\/www.euvolution.com\/prometheism-transhumanism-posthumanism\/transhuman-news-blog\/dna\/macrolones-target-bacterial-ribosomes-and-dna-gyrase-and-can-evade-resistance-mechanisms-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":[26],"tags":[],"class_list":["post-1127530","post","type-post","status-publish","format-standard","hentry","category-dna"],"_links":{"self":[{"href":"https:\/\/www.euvolution.com\/prometheism-transhumanism-posthumanism\/wp-json\/wp\/v2\/posts\/1127530"}],"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=1127530"}],"version-history":[{"count":0,"href":"https:\/\/www.euvolution.com\/prometheism-transhumanism-posthumanism\/wp-json\/wp\/v2\/posts\/1127530\/revisions"}],"wp:attachment":[{"href":"https:\/\/www.euvolution.com\/prometheism-transhumanism-posthumanism\/wp-json\/wp\/v2\/media?parent=1127530"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.euvolution.com\/prometheism-transhumanism-posthumanism\/wp-json\/wp\/v2\/categories?post=1127530"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.euvolution.com\/prometheism-transhumanism-posthumanism\/wp-json\/wp\/v2\/tags?post=1127530"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}