Yury Polikanov, PhD

Research Focus

Our research focuses on uncovering the structure and function of the ribosome, with a particular emphasis on understanding protein synthesis in bacteria, the mechanisms of action of ribosome-targeting antibiotics, and drug resistance at the structural level. While the general process of protein synthesis is well understood, several fundamental questions central to the ribosome structure, function, and evolution remain unanswered. We address these questions using advanced X-ray crystallography and cryo-electron microscopy (cryo-EM) to obtain atomic-resolution structures of bacterial ribosomes in functional complexes with translation factors and antibiotics.

Our work provides detailed insights into how different ribosomal elements work together at the molecular level. By studying ribosome complexes that include natural tRNA substrates, we generate principally new data that reveal the true mechanisms by which antibiotics and translation factors act. Our findings also highlight that studying vacant ribosomes or incomplete comple`xes can lead to misleading conclusions, as critical interactions between antibiotics or factors and the ribosome depend on the presence of natural ribosomal ligands like mRNA and tRNAs. These functionally relevant ribosome complexes not only offer more accurate insights but also improve structural resolution due to the stabilization provided by ribosome-bound tRNAs.

Since our lab was established in 2015, we have published several key papers that unraveled the mechanisms of action of new antibiotics and revised the understanding of some older drugs. Our research aims to achieve a deeper understanding of how the ribosome functions, how antibiotics inhibit it, and how resistance mechanisms develop to overcome drug action. This knowledge will inform the future design of antibiotics that more effectively kill pathogenic bacteria and may offer new strategies for modulating protein synthesis, providing potential therapeutic avenues for various human diseases.

Peer-Reviewed Publications from Independent Career

This section lists only published articles or accepted manuscripts already in press.

* – corresponding author

1. Aleksandrova EV, Syroegin EA, Basu RS, Vassilevski AA, Gagnon MG, and Polikanov YS*. (2024) Mechanism of release factor-mediated peptidyl-tRNA hydrolysis on the ribosome. Under review.
2. Tresco BIC, Wu KJY, Ramkissoon A, Aleksandrova EV, Purdy M, See DNY, Liu RY, Polikanov YS*, and Myers AG*. (2024) Discovery of a broad-spectrum, fluorinated macrobicyclic antibiotic through chemical synthesis. Under review.
3. Huang W, Baliga C, Aleksandrova EV, Atkinson G, Polikanov YS*, Vázquez-Laslop N*, and Mankin AS*. (2024) Ribosome-targeting activity, structure, and diversity of Type II proline-rich antimicrobial peptides from insects. EMBO Reports, accepted.
4. Aleksandrova EV, Ma CX, Klepacki D, Alizadeh F, Vázquez-Laslop N, Liang JH*, Polikanov YS*, and Mankin AS*. (2024) Macrolones target bacterial ribosomes and DNA gyrase and can evade resistance mechanisms.Nature Chemical Biology, published online ahead of print.DOI: 10.1038/s41589-024-01685-3.
5. Batool Z, Pavlova JA, Paranjpe MN, Tereshchenkov AG, Lukianov DA, Osterman IA, Bogdanov AA, Sumbatyan NV*, and Polikanov YS*. (2024) Berberine analog of chloramphenicol exhibits a distinct mode of action and unveils ribosome plasticity.Structure, published online ahead of print.DOI: 10.1016/j.str.2024.06.013.
6. Wu KJY, Tresco BIC, Ramkissoon A, Aleksandrova EV, Syroegin EA, See DNY, Liow P, Dittemore GA, Yu M, Testolin G, Mitcheltree MJ, Liu RY, Svetlov MS, Polikanov YS*, and Myers AG*. (2024) An antibiotic preorganized for ribosomal binding overcomes antimicrobial resistance.Science, 383(6684): 721-726.
7. Aleksandrova EV, Wu KJY, Tresco BIC, Syroegin EA, Killeavy EE, Balasanyants SM, Svetlov MS, Gregory ST, Atkinson GC, Myers AG*, and Polikanov YS*. (2024) Structural basis of Cfr-mediated antimicrobial resistance and mechanisms to evade it.Nature Chemical Biology, 20(7): 867-876.
8. Phelps GA, Cheramie MN, Fernando DM, Selchow P, Meyer CJ, Waidyarachchi SL, Dharuman S, Liu J, Meuli M, Dal Molin M, Killam BY, Murphy PA, Reeve SM, Wilt LA, Anderson SM, Yang L, Lee RB, Temrikar ZH, Lukka PB, Meibohm B, Polikanov YS, Hobbie SN, Böttger EC, Sander P, and Lee RE*. (2024) Development of 2nd generation aminomethyl spectinomycins that overcome native efflux in Mycobacterium abscessus.Proceedings of the National Academy of Sciences USA,121(2): e2314101120.
9. Polikanov YS*, Etheve-Quelquejeu M, and Micura R*. (2023) Synthesis of peptidyl-tRNA mimics for structural biology applications.Accounts of Chemical Research, 56(19): 2713-2725. Review article.
10. Skowron KJ, Baliga C, Johnson T, Kremiller K, Castroverde A, Dean T, Allen A, Lopez-Hernandez A, Aleksandrova EV, Klepacki D, Mankin AS, Polikanov YS, and Moore TW*. (2023) Structure-activity relationships of the antimicrobial peptide natural product apidaecin.Journal of Medicinal Chemistry, 66(17): 11831-11842.
11. Chen CW, Leimer N, Syroegin EA, Dunand C, Bulman ZP, Lewis K, Polikanov YS*, and Svetlov MS*. (2023) Structural insights into the mechanism of overcoming Erm-mediated resistance by macrolides acting in tandem with hygromycin A.Nature Communications, 14(1): 4196.
12. Thaler J, Syroegin EA, Breuker K, Polikanov YS*, and Micura R*. (2023) Practical synthesis of N-formylmethionylated peptidyl-tRNA mimics.ACS Chemical Biology, 18(10): 2233-2239.
13. Vázquez-Laslop N* and Polikanov YS*. (2023) Motif-ation matters.Nature Chemical Biology, 19(9): 1044-1045. News & Views article.
14. Mangano K, Klepacki D, Ohanmu I, Baliga C, Huang W, Brakel A, Krizsan A, Polikanov YS, Hoffmann R*, Vázquez-Laslop N*, and Mankin AS*. (2023) Inhibition of translation termination by the antimicrobial peptide drosocin.Nature Chemical Biology, 19(9): 1082-1090.
15. Paranjpe MN, Marina VI, Grachev AA, Maviza TP, Tolicheva OA, Paleskava A, Osterman IA, Sergiev PV, Konevega AL, Polikanov YS*, and GagnonMG*. (2023) Insights into the molecular mechanism of translation inhibition by the ribosome-targeting antibiotic thermorubin.Nucleic Acids Research, 51(1): 449-462.
16. Syroegin EA, Aleksandrova EV, and Polikanov YS*. (2023) Insights into the ribosome function from the structures of non-stalled ribosome nascent chain complexes.Nature Chemistry, 15(1): 143-153.
17. Syroegin EA, Aleksandrova EV, and Polikanov YS*. (2022) Structural basis for the inability of chloramphenicol to inhibit peptide bond formation in the presence of A-site glycine.Nucleic Acids Research, 50(13): 7669-7679.
18. Syroegin EA, Flemmich L, Klepacki D, Vazquez-Laslop N, Micura R*, and Polikanov YS*. (2022) Structural basis for the context-specific action of the classic peptidyl transferase inhibitor chloramphenicol.Nature Structural & Molecular Biology, 29(2): 152-161.Featured preview by the journal.
19. Lanois-Nouri A, Pantel L, Fu J, Houard J, Ogier JC, Polikanov YS, Racine E, Wang H, Gaudriault S, Givaudan A, and Gualtieri M. (2022) The odilorhabdin antibiotic biosynthetic cluster and acetyltransferase self-resistance locus are niche and species specific.mBio,13(1): e0282621.
20. Mitcheltree MJ, Pisipati A, Syroegin EA, Silvestre KJ, Klepacki D, Mason JD, Terwilliger DW, Testolin G, Pote AR, Wu KJY, Ladley RP, Chatman K, Mankin AS, Polikanov YS*, and Myers AG*. (2021) A synthetic antibiotic class overcoming bacterial multidrug resistance.Nature, 599(7885): 507-512. Featured preview by the journal.
21. Leimer N, Wu X, Imai Y, Morrissette M, Pitt N, Favre-Godal Q, Iinishi A, Jain S, Caboni M, Leus IV, Bonifay V, Niles S, Bargabos R, Ghiglieri M, Corsetti R, Krumpoch M, Fox G, Son S, Klepacki D, Polikanov YS, Freliech CA, McCarthy JE, Edmondson DG, Norris SJ, D’Onofrio A, Hu LT, Zgurskaya HI, and Lewis K*. (2021) A selective antibiotic for Lyme disease.Cell, 184(21): 5405-5418.
22. Balasanyants SM, Aleksandrova EV, and Polikanov YS*. (2021) The role of release factors in the hydrolysis of ester bond in peptidyl-tRNA.Biochemistry (Moscow), 86(9): 1122-1127. Review article.
23. Chen CW, Pavlova JA, Lukianov DA, Tereshchenkov AG, Makarov GI, Khairullina ZZ, Tashlitsky VN, Paleskava A, Konevega AL, Bogdanov AA, Osterman IA*, Sumbatyan NV*, and Polikanov YS*. (2021) Binding and action of triphenylphosphonium analog of chloramphenicol upon the bacterial ribosome.Antibiotics (Basel), 10(4): 390.
24. Svetlov MS, Syroegin EA, Aleksandrova EV, Atkinson GC, Gregory ST, Mankin AS, and Polikanov YS*. (2021) Structure of Erm-modified 70S ribosome reveals the mechanism of macrolide resistance.Nature Chemical Biology, 17(4): 412-420. Featured preview by the journal.
25. Batool Z, Lomakin IB, Polikanov YS*, and Bunick CG*. (2020) Sarecycline interferes with tRNA accommodation and tethers mRNA to the 70S ribosome.Proceedings of the National Academy of Sciences USA, 117(34): 20530-20537.
26. Mardirossian M, Sola R, Beckert B, Valencic E, Collis DWP, Borišek J, Armas F, Di Stasi A, Buchmann J, Syroegin EA, Polikanov YS, Magistrato A, Hilpert K, Wilson DN*, and Scocchi M*. (2020) Peptide inhibitors of bacterial protein synthesis with broad spectrum and SbmA-independent bactericidal activity against clinical pathogens.Journal of Medicinal Chemistry, 63(17): 9590-9602.
27. Osterman IA, Wieland M, Maviza TP, Lashkevich KA, Lukianov DA, Komarova ES, Zakalyukina YV, Buschauer R, Shiriaev DI, Leyn SA, Zlamal JE, Biryukov MV, Skvortsov DA, Tashlitsky VN, Polshakov VI, Cheng J, Polikanov YS, Bogdanov AA, Osterman AL, Dmitriev SE, Beckmann R, Dontsova OA, Wilson DN*, and Sergiev PV*. (2020) Tetracenomycin X inhibits translation by binding within the ribosomal exit tunnel.Nature Chemical Biology, 16(10): 1071-1077.
28. Tamman H, Van Nerom K, Takada H, Vandenberk N, Scholl D, Polikanov YS, Hofkens J, Talavera A, Hauryliuk V*, Hendrix J*, and Garcia-Pino A*. (2020) A nucleotide-switch mechanism mediates opposing catalytic activities of Rel enzymes.Nature Chemical Biology, 16(8): 834-840.
29. Pichkur EB, Paleskava A, Tereshchenkov AG, Kasatsky P, Komarova ES, Shiriaev D, Bogdanov AA, Dontsova OA, Osterman IA, Sergiev PV, PolikanovYS*, Myasnikov AG*, and Konevega AL*. (2020) Insights into the improved macrolide inhibitory activity from the high-resolution cryo-EM structure of dirithromycin bound to the E. coli70S ribosome.RNA Journal, 26(6): 715-723.
30. Eyler DE, Franco MK, Batool Z, Wu MZ, Dubuke ML, Dobosz-Bartoszek M, Jones JD, Polikanov YS*, Roy B*, and Koutmou KS*. (2019) Pseudouridinylation of mRNA coding sequences alters translation.Proceedings of the National Academy of Sciences USA, 116(46): 23068-23074.
31. Travin DY, Watson ZL, Metelev M, Ward FR, Osterman IA, Khven IM, Khabibullina NF, Serebryakova M, Mergaert P, Polikanov YS*, Cate JHD*, and Severinov K*. (2019) Cryo-EM structure of ribosome-bound azole-modified peptide phazolicin rationalizes its species-specific mode of bacterial translation inhibition.Nature Communications, 10(1): 4563.
32. Khabibullina NF, Tereshchenkov AG, Komarova ES, Syroegin EA, Shiriaev DI, Paleskava A, Kartsev VG, Bogdanov AA, Konevega AL, Dontsova OA, Sergiev PV, Osterman IA*, and Polikanov YS*. (2019) Structure of dirithromycin bound to the bacterial ribosome suggests new ways for rational improvement of macrolides.Antimicrobial Agents and Chemotherapy, 63(6): e02266-18.
33. Svetlov MS, Plessa E, Chen CW, Bougas A, Krokidis MG, Dinos GP*, and Polikanov YS*. (2019) High-resolution crystal structures of ribosome-bound chloramphenicol and erythromycin provide the ultimate basis for their competition.RNA Journal, 25(5): 600-606.
34. Matsushita T, Sati G, Kondasinghe N, Pirrone M, Kato T, Waduge P, Kumar H, Sanchon A, Dobosz-Bartoszek M, Shcherbakov D, Juhas M, Hobbie SN, Schrepfer T, Chow CS, Polikanov YS, Schacht J, Vasella A, Böttger EC*, and Crich D*. (2019) Design, multigram synthesis, and in vitroand in vivoevaluation of propylamycin: a semisynthetic 4,5-deoxystreptamine class aminoglycoside for the treatment of drug-resistant Enterobacteriaceae and other Gram-negative pathogens. Journal of American Chemical Society, 141(12): 5051-5061.
35. Juhas M, Widlake E, Teo J, Huseby DL, Tyrrell JM, Polikanov YS, Ercan O, Petersson A, Cao S, Aboklaish AF, Rominski A, Crich D, Böttger EC, Walsh TR, Hughes D, and Hobbie SN*. (2019) In vitroactivity of apramycin against multidrug-, carbapenem- and aminoglycoside-resistant Enterobacteriaceae and Acinetobacter baumannii.Journal of Antimicrobial Chemotherapy, 74(4): 944-952.
36. Melnikov SV, Khabibullina NF, Mairhofer E, Vargas-Rodriguez O, Reynolds NM, Micura R*, Söll D*, and Polikanov YS*. (2019) Mechanistic insights into the slow peptide bond formation with D-amino acids in the ribosomal active site.Nucleic Acids Research, 47(4): 2089-2100.
37. Pantel L, Florin T, Dobosz-Bartoszek M, Racine E, Sarciaux M, Serri M, Houard J, Campagne JM, Marcia de Figueiredo R, Midrier C, Gaudriault S, Givaudan A, Lanois A, Forst S, Aumelas A, Cotteaux-Lautard C, Bolla JM, Vingsbo Lundberg C, Huseby DL, Hughes D, Villain-Guillot P, Mankin AS*, Polikanov YS*, and Gualtieri M*. (2018) Odilorhabdins, antibacterial agents that cause miscoding by binding at a new ribosomal site.Molecular Cell, 70(1): 83-94. Featured preview by the journal.
38. Lin J, Zhou D, Steitz TA*, Polikanov YS*, and Gagnon MG*. (2018) Ribosome-targeting antibiotics: Modes of action, mechanisms of resistance, and implications for drug design.Annual Review of Biochemistry, 87: 451-478. Review article.
39. Polikanov YS*, Aleksashin NA, Beckert B, and Wilson DN*. (2018) The mechanisms of action of ribosome-targeting peptide antibiotics.Frontiers in Molecular Biosciences, 5: 48. Review article.
40. Tereshchenkov AG, Dobosz-Bartoszek M, Osterman IA, Marks J, Sergeeva VA, Kasatsky P, Komarova ES, Stavrianidi AA, Rodin IA, Konevega AL, Sergiev PV, Sumbatyan NV, Mankin AS, Bogdanov AA*, and Polikanov YS*. (2018) Binding and action of amino acid analogs of chloramphenicol upon the bacterial ribosome.Journal of Molecular Biology, 430(6): 842-852.
41. Sergiev PV, Aleksashin NA, Chugunova AA, Polikanov YS*, and DontsovaOA*. (2018) Structural and evolutionary insights into ribosomal RNA methylation.Nature Chemical Biology, 14(3): 226-235.
42. Metelev M, Osterman IA, Ghilarov D, Khabibullina NF, Yakimov A, Shabalin K, Utkina I, Travin DY, Komarova ES, Serebryakova M, Artamonova T, Khodorkovskii M, Konevega AL, Sergiev PV, Severinov K*, and Polikanov YS*. (2017) Klebsazolicin inhibits 70S ribosome by obstructing the peptide exit tunnel.Nature Chemical Biology, 13(10): 1129-1136. Featured preview by the journal.
43. Almutairi MM, Svetlov MS, Hansen DA, Khabibullina NF, Klepacki D, Kang HY, Sherman DH, Vázquez-Laslop N, Polikanov YS*, and Mankin AS*. (2017) Co-produced natural ketolides methymycin and pikromycin inhibit bacterial growth by preventing synthesis of a limited number of proteins.Nucleic Acids Research, 45(16): 9573-9582.
44. Osterman IA, Khabibullina NF, Komarova ES, Kasatsky P, Kartsev VG, Bogdanov AA, Dontsova OA, Konevega AL*, Sergiev PV*, and Polikanov YS*. (2017) Madumycin II inhibits peptide bond formation by forcing the peptidyl transferase center into an inactive state.Nucleic Acids Research, 45(12): 7507-7514.
45. Karabadzhak AG, Petti LM, Barrera FN, Edwards APB, Moya-Rodríguez A, Polikanov YS, Freites JA, Tobias DJ, Engelman DM*, and DiMaio D*. (2017) Two transmembrane dimers of the bovine papillomavirus E5 oncoprotein clamp the PDGF β receptor in an active dimeric conformation.Proceedings of the National Academy of Sciences USA, 114(35): E7262-7271.
46. Arenz S, Juette MF, Graf M, Nguyen F, Huter P, Polikanov YS*, Blanchard SC*, and Wilson DN*. (2016) Structures of the orthosomycin antibiotics avilamycin and evernimicin in complex with the bacterial 70S ribosome.Proceedings of the National Academy of Sciences USA, 113(27): 7527-7532.
47. Melnikov SV, Söll D, Steitz TA*, and Polikanov YS*. (2016) Insights into RNA binding by the anticancer drug cisplatin from the crystal structure of cisplatin-modified ribosome.Nucleic Acids Research, 44(10): 4978-4987.

Peer-Reviewed Publications from Postdoctoral Stage (2008-2015)

48. Polikanov YSand Moore PB*. (2015) Acoustic vibrations contribute to the diffuse scatter produced by ribosome crystals. Acta Crystallographica Section D, 71(Pt 10): 2021-2031.
49. Polikanov YS, Starosta AL, Juette MF, Altman RB, Terry DS, Lu W, Burnett BJ, Dinos G, Reynolds K, Blanchard SC*, Steitz TA*, and Wilson DN*. (2015) Distinct tRNA accommodation intermediates observed on the ribosome with the antibiotics Hygromycin A and A201A.Molecular Cell, 58(5): 832-844.
50. Polikanov YS, Melnikov SV, Söll D*, and Steitz TA*. (2015) Structural insights into the role of rRNA modifications in protein synthesis and ribosome assembly.Nature Structural & Molecular Biology, 22(4): 342-344.
51. Polikanov YS, Osterman IA, Szal T, Tashlitsky VN, Serebryakova MV, Kusochek P, Bulkley D, Malanicheva IA, Efimenko TA, Efremenkova OV, Konevega AL, Shaw KJ, Bogdanov AA, Rodnina MV, Dontsova OA, Mankin AS*, Steitz TA*, and Sergiev PV*. (2014) Amicoumacin A inhibits translation by stabilizing mRNA interaction with the ribosome.Molecular Cell, 56(4): 531-540.
52. Polikanov YS, Szal T, Jiang F, Gupta P, Matsuda R, Shiozuka M, Steitz TA*, Vázquez-Laslop N*, and Mankin AS*. (2014) Negamycin interferes with decoding and translocation by simultaneous interaction with rRNA and tRNA.Molecular Cell, 56(4): 541-550.
53. Polikanov YS, Steitz TA*, and Innis CA*. (2014) A proton wire to couple aminoacyl-tRNA accommodation and peptide-bond formation on the ribosome.Nature Structural & Molecular Biology, 21(9): 787-793. Selected for the cover image.
54. Bulkley D, Brandi L, Polikanov YS, Fabbretti A, O’Connor M, Gualerzi CO*, and Steitz TA*. (2014) The antibiotics dityromycin and GE82832 bind protein S12 and block EF-G-catalyzed translocation.Cell Reports, S2211-1247(13): 358-365.
55. Blaha GM,Polikanov YS, and Steitz TA*. (2012) Elements of ribosomal drug resistance and specificity.Current Opinion in Structural Biology, 22(6): 750-758. Equal first-author contribution. Review article.
56. Polikanov YS, Blaha GM, and Steitz TA*. (2012) How hibernation factors RMF, HPF, and YfiA turn off protein synthesis.Science, 336(6083): 915-918.

Peer-Reviewed Publications from Graduate Research (2004-2008)

57. Nizovtseva EV, Clauvelin N, Todolli S, Polikanov YS, Kulaeva OI, Wengrzynek S, Olson WK*, and Studitsky VM*. (2017) Nucleosome-free DNA regions differentially affect distant communication in chromatin.Nucleic Acids Research, 45(6): 3059-3067.
58. Kulaeva OI, Nizovtseva EV, Polikanov YS, Ulianov SV, and Studitsky VM*. (2012) Distant activation of transcription: mechanisms of enhancer action.Molecular and Cellular Biology, 32(24): 4892-4897.
59. Kulaeva OI, Zheng G, Polikanov YS, Colasanti AV, Clauvelin N, Mukhopadhyay S, Sengupta AM, Studitsky VM*, and Olson WK*. (2011) Internucleosomal interactions mediated by histone tails allow distant communication in chromatin.Journal of Biological Chemistry, 287(24): 20248-20257.
60. Polikanov YSand Studitsky VM*. (2009) Analysis of distant communication on defined chromatin templates in vitro. Methods in Molecular Biology, 543: 563-576.
61. Polikanov YS, Bondarenko VA, Tchernajenko V, Jiang YI, Lutter LC, Vologodskii A*, and Studitsky VM*. (2007) Probability of the site juxtaposition determines the rate of protein-mediated DNA looping.Biophysical Journal, 93(8): 2726-2731.
62. Polikanov YS, Rubtsov MA, and Studitsky VM*. (2007) Biochemical analysis of enhancer-promoter communication in chromatin.Methods, 41(3): 250-258.
63. Rubtsov MA, Polikanov YS, Bondarenko VA, Wang YH*, and Studitsky VM*. (2006) Chromatin structure can strongly facilitate enhancer action over a distance.Proceedings of the National Academy of Sciences USA, 103(47): 17690-17695. Equal first-author contribution.
64. Bondarenko VA, Steele LM, Ujvari A, Gaykalova DA, Kulaeva OI, Polikanov YS, Luse DS*, and Studitsky VM*. (2006) Nucleosomes can form a polar barrier to transcript elongation by RNA polymerase II.Molecular Cell, 24(3): 469-479.

Post-Doctoral Training, Yale University

PhD, University of Medicine and Dentistry of New Jersey and Rutgers University

MS, Lomonosov Moscow State University, Russia