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Structural insights into species-specific features of the ribosome from the pathogen Staphylococcus aureus.

Eyal Z, Matzov D, Krupkin M, Wekselman I, Paukner S, Zimmerman E, Rozenberg H, Bashan A, Yonath A
Proc Natl Acad Sci U S A 112 E5805-14 (2015)
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Cited: 73 times
EuropePMC logo PMID: 26464510

Abstract

The emergence of bacterial multidrug resistance to antibiotics threatens to cause regression to the preantibiotic era. Here we present the crystal structure of the large ribosomal subunit from Staphylococcus aureus, a versatile Gram-positive aggressive pathogen, and its complexes with the known antibiotics linezolid and telithromycin, as well as with a new, highly potent pleuromutilin derivative, BC-3205. These crystal structures shed light on specific structural motifs of the S. aureus ribosome and the binding modes of the aforementioned antibiotics. Moreover, by analyzing the ribosome structure and comparing it with those of nonpathogenic bacterial models, we identified some unique internal and peripheral structural motifs that may be potential candidates for improving known antibiotics and for use in the design of selective antibiotic drugs against S. aureus.

Articles - 4wce mentioned but not cited (13)

  1. Structural insights into species-specific features of the ribosome from the pathogen Staphylococcus aureus. Eyal Z, Matzov D, Krupkin M, Wekselman I, Paukner S, Zimmerman E, Rozenberg H, Bashan A, Yonath A. Proc Natl Acad Sci U S A 112 E5805-14 (2015)
  2. A novel pleuromutilin antibacterial compound, its binding mode and selectivity mechanism. Eyal Z, Matzov D, Krupkin M, Paukner S, Riedl R, Rozenberg H, Zimmerman E, Bashan A, Yonath A. Sci Rep 6 39004 (2016)
  3. Structure of the 70S ribosome from human pathogen Staphylococcus aureus. Khusainov I, Vicens Q, Bochler A, Grosse F, Myasnikov A, Ménétret JF, Chicher J, Marzi S, Romby P, Yusupova G, Yusupov M, Hashem Y. Nucleic Acids Res 44 10491-10504 (2016)
  4. Structural insights of lincosamides targeting the ribosome of Staphylococcus aureus. Matzov D, Eyal Z, Benhamou RI, Shalev-Benami M, Halfon Y, Krupkin M, Zimmerman E, Rozenberg H, Bashan A, Fridman M, Yonath A. Nucleic Acids Res 45 10284-10292 (2017)
  5. Structural Basis for Linezolid Binding Site Rearrangement in the Staphylococcus aureus Ribosome. Belousoff MJ, Eyal Z, Radjainia M, Ahmed T, Bamert RS, Matzov D, Bashan A, Zimmerman E, Mishra S, Cameron D, Elmlund H, Peleg AY, Bhushan S, Lithgow T, Yonath A. mBio 8 e00395-17 (2017)
  6. Avilamycin and evernimicin induce structural changes in rProteins uL16 and CTC that enhance the inhibition of A-site tRNA binding. Krupkin M, Wekselman I, Matzov D, Eyal Z, Diskin Posner Y, Rozenberg H, Zimmerman E, Bashan A, Yonath A. Proc Natl Acad Sci U S A 113 E6796-E6805 (2016)
  7. Thioredoxin Profiling of Multiple Thioredoxin-Like Proteins in Staphylococcus aureus. Peng H, Zhang Y, Trinidad JC, Giedroc DP. Front Microbiol 9 2385 (2018)
  8. Directed evolution of the rRNA methylating enzyme Cfr reveals molecular basis of antibiotic resistance. Tsai K, Stojković V, Noda-Garcia L, Young ID, Myasnikov AG, Kleinman J, Palla A, Floor SN, Frost A, Fraser JS, Tawfik DS, Fujimori DG. Elife 11 e70017 (2022)
  9. Discovery of small-molecule inhibitors targeting the ribosomal peptidyl transferase center (PTC) of M. tuberculosis. Tam B, Sherf D, Cohen S, Eisdorfer SA, Perez M, Soffer A, Vilenchik D, Akabayov SR, Wagner G, Akabayov B. Chem Sci 10 8764-8767 (2019)
  10. Machine learning approaches to optimize small-molecule inhibitors for RNA targeting. Grimberg H, Tiwari VS, Tam B, Gur-Arie L, Gingold D, Polachek L, Akabayov B. J Cheminform 14 4 (2022)
  11. Structural Studies Reveal the Role of Helix 68 in the Elongation Step of Protein Biosynthesis. Cimicata G, Fridkin G, Bose T, Eyal Z, Halfon Y, Breiner-Goldstein E, Fox T, Zimmerman E, Bashan A, de Val N, Wlodawer A, Yonath A. mBio 13 e0030622 (2022)
  12. DoubleHelix: nucleic acid sequence identification, assignment and validation tool for cryo-EM and crystal structure models. Chojnowski G. Nucleic Acids Res 51 8255-8269 (2023)
  13. Molecular Mechanism of Staphylococcus xylosus Resistance Against Tylosin and Florfenicol. Chen M, Li Y, Li S, Cui W, Zhou Y, Qu Q, Che R, Li L, Yuan S, Liu X. Infect Drug Resist 15 6165-6176 (2022)


Reviews citing this publication (14)

  1. How Macrolide Antibiotics Work. Vázquez-Laslop N, Mankin AS. Trends Biochem Sci 43 668-684 (2018)
  2. Ribosome-Targeting Antibiotics: Modes of Action, Mechanisms of Resistance, and Implications for Drug Design. Lin J, Zhou D, Steitz TA, Polikanov YS, Gagnon MG. Annu Rev Biochem 87 451-478 (2018)
  3. Pleuromutilins: Potent Drugs for Resistant Bugs-Mode of Action and Resistance. Paukner S, Riedl R. Cold Spring Harb Perspect Med 7 a027110 (2017)
  4. Lefamulin: Review of a Promising Novel Pleuromutilin Antibiotic. Veve MP, Wagner JL. Pharmacotherapy 38 935-946 (2018)
  5. Lincosamides, Streptogramins, Phenicols, and Pleuromutilins: Mode of Action and Mechanisms of Resistance. Schwarz S, Shen J, Kadlec K, Wang Y, Brenner Michael G, Feßler AT, Vester B. Cold Spring Harb Perspect Med 6 a027037 (2016)
  6. Antibacterial properties and clinical potential of pleuromutilins. Goethe O, Heuer A, Ma X, Wang Z, Herzon SB. Nat Prod Rep 36 220-247 (2019)
  7. ABC-F translation factors: from antibiotic resistance to immune response. Fostier CR, Monlezun L, Ousalem F, Singh S, Hunt JF, Boël G. FEBS Lett 595 675-706 (2021)
  8. A Bright Future for Antibiotics? Matzov D, Bashan A, Yonath A. Annu Rev Biochem 86 567-583 (2017)
  9. Antibiotics and Bacterial Resistance-A Short Story of an Endless Arms Race. Baran A, Kwiatkowska A, Potocki L. Int J Mol Sci 24 5777 (2023)
  10. Antibiotics targeting bacterial ribosomal subunit biogenesis. Champney WS. J Antimicrob Chemother 75 787-806 (2020)
  11. Binding site comparisons for target-centered drug discovery. Konc J. Expert Opin Drug Discov 14 445-454 (2019)
  12. Clinical Utility of Lefamulin: If Not Now, When? Mercuro NJ, Veve MP. Curr Infect Dis Rep 22 25 (2020)
  13. Ribosomal Antibiotics: Contemporary Challenges. Auerbach-Nevo T, Baram D, Bashan A, Belousoff M, Breiner E, Davidovich C, Cimicata G, Eyal Z, Halfon Y, Krupkin M, Matzov D, Metz M, Rufayda M, Peretz M, Pick O, Pyetan E, Rozenberg H, Shalev-Benami M, Wekselman I, Zarivach R, Zimmerman E, Assis N, Bloch J, Israeli H, Kalaora R, Lim L, Sade-Falk O, Shapira T, Taha-Salaime L, Tang H, Yonath A. Antibiotics (Basel) 5 E24 (2016)
  14. Staph wars: the antibiotic pipeline strikes back. Douglas EJA, Laabei M. Microbiology (Reading) 169 (2023)

Articles citing this publication (46)

  1. A platform for the discovery of new macrolide antibiotics. Seiple IB, Zhang Z, Jakubec P, Langlois-Mercier A, Wright PM, Hog DT, Yabu K, Allu SR, Fukuzaki T, Carlsen PN, Kitamura Y, Zhou X, Condakes ML, Szczypiński FT, Green WD, Myers AG. Nature 533 338-345 (2016)
  2. The cryo-EM structure of hibernating 100S ribosome dimer from pathogenic Staphylococcus aureus. Matzov D, Aibara S, Basu A, Zimmerman E, Bashan A, Yap MF, Amunts A, Yonath AE. Nat Commun 8 723 (2017)
  3. Revising the Structural Diversity of Ribosomal Proteins Across the Three Domains of Life. Melnikov S, Manakongtreecheep K, Söll D. Mol Biol Evol 35 1588-1598 (2018)
  4. Kinetics of drug-ribosome interactions defines the cidality of macrolide antibiotics. Svetlov MS, Vázquez-Laslop N, Mankin AS. Proc Natl Acad Sci U S A 114 13673-13678 (2017)
  5. Structural insights into species-specific features of the ribosome from the human pathogen Mycobacterium tuberculosis. Yang K, Chang JY, Cui Z, Li X, Meng R, Duan L, Thongchol J, Jakana J, Huwe CM, Sacchettini JC, Zhang J. Nucleic Acids Res 45 10884-10894 (2017)
  6. Structures of the orthosomycin antibiotics avilamycin and evernimicin in complex with the bacterial 70S ribosome. Arenz S, Juette MF, Graf M, Nguyen F, Huter P, Polikanov YS, Blanchard SC, Wilson DN. Proc Natl Acad Sci U S A 113 7527-7532 (2016)
  7. Exit tunnel modulation as resistance mechanism of S. aureus erythromycin resistant mutant. Halfon Y, Matzov D, Eyal Z, Bashan A, Zimmerman E, Kjeldgaard J, Ingmer H, Yonath A. Sci Rep 9 11460 (2019)
  8. In Vitro Activity of Lefamulin Tested against Streptococcus pneumoniae with Defined Serotypes, Including Multidrug-Resistant Isolates Causing Lower Respiratory Tract Infections in the United States. Mendes RE, Farrell DJ, Flamm RK, Talbot GH, Ivezic-Schoenfeld Z, Paukner S, Sader HS. Antimicrob Agents Chemother 60 4407-4411 (2016)
  9. A computational knowledge-base elucidates the response of Staphylococcus aureus to different media types. Seif Y, Monk JM, Mih N, Tsunemoto H, Poudel S, Zuniga C, Broddrick J, Zengler K, Palsson BO. PLoS Comput Biol 15 e1006644 (2019)
  10. Structural basis for context-specific inhibition of translation by oxazolidinone antibiotics. Tsai K, Stojković V, Lee DJ, Young ID, Szal T, Klepacki D, Vázquez-Laslop N, Mankin AS, Fraser JS, Fujimori DG. Nat Struct Mol Biol 29 162-171 (2022)
  11. Lefamulin. Comment on: "Novel Antibiotics for Multidrug-Resistant Gram-Positive Microorganisms. Microorganisms, 2019, 7, 270". Koulenti D, Xu E, Yin Sum Mok I, Song A, Karageorgopoulos DE, Armaganidis A, Lipman J, Tsiodras S. Microorganisms 7 E386 (2019)
  12. Low Prevalence of Gram-Positive Isolates Showing Elevated Lefamulin MIC Results during the SENTRY Surveillance Program for 2015-2016 and Characterization of Resistance Mechanisms. Mendes RE, Paukner S, Doyle TB, Gelone SP, Flamm RK, Sader HS. Antimicrob Agents Chemother 63 e02158-18 (2019)
  13. Structure of Pseudomonas aeruginosa ribosomes from an aminoglycoside-resistant clinical isolate. Halfon Y, Jimenez-Fernandez A, La Rosa R, Espinosa Portero R, Krogh Johansen H, Matzov D, Eyal Z, Bashan A, Zimmerman E, Belousoff M, Molin S, Yonath A. Proc Natl Acad Sci U S A 116 22275-22281 (2019)
  14. Structure of the 70S Ribosome from the Human Pathogen Acinetobacter baumannii in Complex with Clinically Relevant Antibiotics. Nicholson D, Edwards TA, O'Neill AJ, Ranson NA. Structure 28 1087-1100.e3 (2020)
  15. Characterization of the Core Ribosomal Binding Region for the Oxazolidone Family of Antibiotics Using Cryo-EM. Wright A, Deane-Alder K, Marschall E, Bamert R, Venugopal H, Lithgow T, Lupton DW, Belousoff MJ. ACS Pharmacol Transl Sci 3 425-432 (2020)
  16. Comparative proteomic analysis reveals drug resistance of Staphylococcus xylosus ATCC700404 under tylosin stress. Liu X, Wang J, Chen M, Che R, Ding W, Yu F, Zhou Y, Cui W, Xiaoxu X, God'spower BO, Li Y. BMC Vet Res 15 224 (2019)
  17. Coenzyme Q0 From Antrodia cinnamomea Exhibits Drug-Resistant Bacteria Eradication and Keratinocyte Inflammation Mitigation to Ameliorate Infected Atopic Dermatitis in Mouse. Chou WL, Lee TH, Huang TH, Wang PW, Chen YP, Chen CC, Chang ZY, Fang JY, Yang SC. Front Pharmacol 10 1445 (2019)
  18. Cryo-electron microscopy structure of the 70S ribosome from Enterococcus faecalis. Murphy EL, Singh KV, Avila B, Kleffmann T, Gregory ST, Murray BE, Krause KL, Khayat R, Jogl G. Sci Rep 10 16301 (2020)
  19. The Ribosomal Protein uL22 Modulates the Shape of the Protein Exit Tunnel. Wekselman I, Zimmerman E, Davidovich C, Belousoff M, Matzov D, Krupkin M, Rozenberg H, Bashan A, Friedlander G, Kjeldgaard J, Ingmer H, Lindahl L, Zengel JM, Yonath A. Structure 25 1233-1241.e3 (2017)
  20. Hibernation-Promoting Factor Sequesters Staphylococcus aureus Ribosomes to Antagonize RNase R-Mediated Nucleolytic Degradation. Lipońska A, Yap MF. mBio 12 e0033421 (2021)
  21. cryoEM-Guided Development of Antibiotics for Drug-Resistant Bacteria. Belousoff MJ, Venugopal H, Wright A, Seoner S, Stuart I, Stubenrauch C, Bamert RS, Lupton DW, Lithgow T. ChemMedChem 14 527-531 (2019)
  22. A long-distance rRNA base pair impacts the ability of macrolide antibiotics to kill bacteria. Svetlov MS, Cohen S, Alsuhebany N, Vázquez-Laslop N, Mankin AS. Proc Natl Acad Sci U S A 117 1971-1975 (2020)
  23. Synthesis and Biological Activity Evaluation of Novel Heterocyclic Pleuromutilin Derivatives. Yi Y, Fu Y, Dong P, Qin W, Liu Y, Liang J, Shang R. Molecules 22 E996 (2017)
  24. Synthesis, Antibacterial Activities, Mode of Action and Acute Toxicity Studies of New Oxazolidinone-Fluoroquinolone Hybrids. Liu L, Shao L, Li J, Cui H, Li B, Zhou X, Lv P, Zhang J. Molecules 24 E1641 (2019)
  25. Different Resistance Mechanisms for Cadazolid and Linezolid in Clostridium difficile Found by Whole-Genome Sequencing Analysis. Caspers P, Locher HH, Pfaff P, Diggelmann S, Rueedi G, Bur D, Ritz D. Antimicrob Agents Chemother 61 e00384-17 (2017)
  26. Discovery of natural-product-derived sequanamycins as potent oral anti-tuberculosis agents. Zhang J, Lair C, Roubert C, Amaning K, Barrio MB, Benedetti Y, Cui Z, Xing Z, Li X, Franzblau SG, Baurin N, Bordon-Pallier F, Cantalloube C, Sans S, Silve S, Blanc I, Fraisse L, Rak A, Jenner LB, Yusupova G, Yusupov M, Zhang J, Kaneko T, Yang TJ, Fotouhi N, Nuermberger E, Tyagi S, Betoudji F, Upton A, Sacchettini JC, Lagrange S. Cell 186 1013-1025.e24 (2023)
  27. LSTrAP-Crowd: prediction of novel components of bacterial ribosomes with crowd-sourced analysis of RNA sequencing data. Hew B, Tan QW, Goh W, Ng JWX, Mutwil M. BMC Biol 18 114 (2020)
  28. Toward the rational design of macrolide antibiotics to combat resistance. Pavlova A, Parks JM, Oyelere AK, Gumbart JC. Chem Biol Drug Des 90 641-652 (2017)
  29. A Structurally Characterized Staphylococcus aureus Evolutionary Escape Route from Treatment with the Antibiotic Linezolid. Perlaza-Jiménez L, Tan KS, Piper SJ, Johnson RM, Bamert RS, Stubenrauch CJ, Wright A, Lupton D, Lithgow T, Belousoff MJ. Microbiol Spectr 10 e0058322 (2022)
  30. A noncanonical binding site of linezolid revealed via molecular dynamics simulations. Makarov GI, Makarova TM. J Comput Aided Mol Des 34 281-291 (2020)
  31. Combined Effect of the Cfr Methyltransferase and Ribosomal Protein L3 Mutations on Resistance to Ribosome-Targeting Antibiotics. Pakula KK, Hansen LH, Vester B. Antimicrob Agents Chemother 61 e00862-17 (2017)
  32. Cryo-EM structure of Mycobacterium tuberculosis 50S ribosomal subunit bound with clarithromycin reveals dynamic and specific interactions with macrolides. Zhang W, Li Z, Sun Y, Cui P, Liang J, Xing Q, Wu J, Xu Y, Zhang W, Zhang Y, He L, Gao N. Emerg Microbes Infect 11 293-305 (2022)
  33. Cryo-EM structure of the ancient eukaryotic ribosome from the human parasite Giardia lamblia. Hiregange DG, Rivalta A, Bose T, Breiner-Goldstein E, Samiya S, Cimicata G, Kulakova L, Zimmerman E, Bashan A, Herzberg O, Yonath A. Nucleic Acids Res 50 1770-1782 (2022)
  34. In vitro antibacterial activity of α-methoxyimino acylide derivatives against macrolide-resistant pathogens and mutation analysis in 23S rRNA. Sugiyama H, Yoshida I, Ueki M, Tanabe K, Manaka A, Hiramatsu K. J Antibiot (Tokyo) 70 264-271 (2017)
  35. Structure-Uptake Relationship Studies of Oxazolidinones in Gram-Negative ESKAPE Pathogens. Hu Z, Leus IV, Chandar B, Sherborne BS, Avila QP, Rybenkov VV, Zgurskaya HI, Duerfeldt AS. J Med Chem 65 14144-14179 (2022)
  36. A click chemistry approach to pleuromutilin derivatives, evaluation of anti-MRSA activity and elucidation of binding mode by surface plasmon resonance and molecular docking. Zhang Z, Zhang ZS, Wang X, Xi GL, Jin Z, Tang YZ. J Enzyme Inhib Med Chem 36 2087-2103 (2021)
  37. Characterization of Linezolid-Analogue L3-Resistance Mutation in Staphylococcus aureus. Zanfardino A, Di Napoli M, Migliore F, Hay Mele B, Soriente A, De Rosa M, Notomista E, Varcamonti M. Microorganisms 11 700 (2023)
  38. Comparative Assessment of Docking Programs for Docking and Virtual Screening of Ribosomal Oxazolidinone Antibacterial Agents. Buckley ME, Ndukwe ARN, Nair PC, Rana S, Fairfull-Smith KE, Gandhi NS. Antibiotics (Basel) 12 463 (2023)
  39. Contezolid, a novel oxazolidinone antibiotic, may improve drug-related thrombocytopenia in clinical antibacterial treatment. Li B, Liu Y, Luo J, Cai Y, Chen M, Wang T. Front Pharmacol 14 1157437 (2023)
  40. Finding priority bacterial ribosomes for future structural and antimicrobial research based upon global RNA and protein sequence analysis. Cooper HB, Krause KL, Gardner PP. PeerJ 11 e14969 (2023)
  41. Identification and characterization of RNA pentaloop sequence families. Saon M, Kirkpatrick CC, Znosko BM. NAR Genom Bioinform 5 lqac102 (2023)
  42. Improving antibacterial ability of Ti-Cu thin films with co-sputtering method. Mahmoudi-Qashqay S, Zamani-Meymian MR, Sadati SJ. Sci Rep 13 16593 (2023)
  43. MolOptimizer: A Molecular Optimization Toolkit for Fragment-Based Drug Design. Soffer A, Viswas SJ, Alon S, Rozenberg N, Peled A, Piro D, Vilenchik D, Akabayov B. Molecules 29 276 (2024)
  44. Proteomic and Phenotypic Studies of Mycoplasma pneumoniae Revealed Macrolide-Resistant Mutation (A2063G) Associated Changes in Protein Composition and Pathogenicity of Type I Strains. Zhang Z, Dou H, Yuan Q, Shi D, Wan R, Tu P, Xin D, Guo S. Microbiol Spectr 11 e0461322 (2023)
  45. Structural conservation of antibiotic interaction with ribosomes. Paternoga H, Crowe-McAuliffe C, Bock LV, Koller TO, Morici M, Beckert B, Myasnikov AG, Grubmüller H, Nováček J, Wilson DN. Nat Struct Mol Biol 30 1380-1392 (2023)
  46. The redesign of oxazolidinone antibiotics in response to Staphylococcus aureus. Lupton D, Belousoff MJ. Future Microbiol 12 1113-1117 (2017)


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