Actinobacteria of the genus Streptomyces – a reservoir of aminoglycoside acetyltransferase genes

Cover Page

Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription Access

Abstract

The lack of success in combating the spread of multidrug resistance in pathogenic bacteria forces the scientific community to analyze at a new level of knowledge the mechanisms, routes of spread and natural reservoirs containing bacteria that carry antibiotic resistance genes. The classical mechanism of resistance to aminoglycoside antibiotics (AG) is the modification of AG by enzymes, the most common and clinically significant of which are aminoglycoside acetyltransferases (AAC). In this study, genes encoding enzymes belonging to the AAC(2'), AAC(3), AAC(6') and Eis subfamilies were identified in the sequenced genomes of Streptomyces strains producing AG. Comparative analysis of amino acid sequences showed that the closest homologues for the identified AAC are acetyltransferases from other species of actinobacteria of the genus Streptomyces that do not produce AG (producers of other classes of antibiotics or not producing antibiotics). Comparative phylogenetic analysis of amino acid sequences showed that the enzymes AAC(2′) and Eis are homologues of the acetyltransferases AAC(2′)-I and Eis, previously identified in mycobacteria. The possible role of Eis acetyltransferases in the acetylation of various substrates upon entry into the human body through vesicles containing them is discussed.

Full Text

Restricted Access

About the authors

M. G. Alekseeva

Vavilov Institute of General Genetics, Russian Academy of Sciences

Author for correspondence.
Email: Alekseevamg@mail.ru
Russian Federation, 119991, Moscow

A. V. Ratkin

Vavilov Institute of General Genetics, Russian Academy of Sciences

Email: Alekseevamg@mail.ru
Russian Federation, 119991, Moscow

O. O. Galanova

Vavilov Institute of General Genetics, Russian Academy of Sciences

Email: Alekseevamg@mail.ru
Russian Federation, 119991, Moscow

V. N. Danilenko

Vavilov Institute of General Genetics, Russian Academy of Sciences

Email: Alekseevamg@mail.ru
Russian Federation, 119991, Moscow

References

  1. Serio A.W., Keepers T., Andrews L. et al. Aminoglycoside revival: Review of a historically important class of antimicrobials undergoing rejuvenation // EcoSal. Plus. 2018. V. 8. № 1. https://doi.org/10.1128/ecosalplus.ESP-0002-2018
  2. Ramirez M.S., Tolmasky M.E. Aminoglycoside modifying enzymes // Drug. Resist. Updat. 2010. V. 13. № 6. P. 151–171. https://doi.org/10.1016/j.drup.2010.08.003
  3. Webster C.M., Shepherd M. A mini-review: Environmental and metabolic factors affecting aminoglycoside efficacy // World J. Microbiol. Biotechnol. 2022. V. 39. № 1. P. 7. https://doi.org/10.1007/s11274-022-03445-8
  4. Hotta K., Kondo S. Kanamycin and its derivative, arbekacin: Significance and impact // J. Antibiot. (Tokyo). 2018. V. 71. № 4. P. 417–424. https://doi.org/10.1038/s41429-017-0017-8
  5. Рудакова Н.Н., Алексеева М.Г., Даниленко В.Н. Гены аминогликозидфосфотрансфераз у почвенных бактерий рода Streptomyces // Успехи совр. биологии. 2020. T. 140. № 3. С. 211–224. https://doi.org/10.31857/S0042132420020064
  6. Sękowska A. In vitro activity of plazomicin and other aminoglycosides against Klebsiella pneumoniae multidrug-resistant strains // J. Antibiot. (Tokyo). 2024. V. 77. № 8. P. 548–551. https://doi.org/10.1038/s41429-024-00734-2.
  7. Garneau-Tsodikova S., Labby K.J. Mechanisms of resistance to aminoglycoside antibiotics: Overview and perspectives // Medchemcomm. 2016. V. 7. № 1. P. 11–27. https://doi.org/10.1039/C5MD00344J
  8. Pradier L., Bedhomme S. Ecology, more than antibiotics consumption, is the major predictor for the global distribution of aminoglycoside-modifying enzymes // Elife. 2023. V. 12. https://doi.org/10.7554/eLife.77015
  9. Durand G.A., Raoult D., Dubourg G. Antibiotic discovery: History, methods and perspectives // Int. J. Antimicrob. Agents. 2019. V. 53. № 4. P. 371–382. https://doi.org/10.1016/j.ijantimicag.2018.11.010
  10. Meyer K.J., Nodwell J.R. Streptomyces extracellular vesicles are a broad and permissive antimicrobial packaging and delivery system // J. Bacteriol. 2024. V. 206. № 3. https://doi.org/10.1128/jb.00325-23
  11. Ogawara H. Comparison of antibiotic resistance mechanisms in antibiotic-producing and pathogenic bacteria // Molecules. 2019. V. 24. № 19. https://doi.org/10.3390/molecules24193430
  12. Sanz-García F., Anoz-Carbonell E., Pérez-Herrán E. et al. Mycobacterial aminoglycoside acetyltransferases: A little of drug resistance, and a lot of other roles // Front. Microbiol. 2019. V. 10. https://doi.org/10.3389/fmicb.2019.00046
  13. Pan Q., Zhao F.L., Ye B.C. Eis, a novel family of arylalkylamine N-acetyltransferase (EC 2.3.1.87) // Sci. Rep. 2018. V. 8. № 1. P. 2435. https://doi.org/10.1038/s41598-018-20802-6
  14. Darby E.M., Trampari E., Siasat P. et al. Molecular mechanisms of antibiotic resistance revisited // Nat. Rev. Microbiol. 2023. V. 21. № 5. P. 280–295. https://doi.org/10.1038/s41579-022-00820-y
  15. d'Udekem d'Acoz O., Hue F., Ye T. et al. Dynamics and quantitative contribution of the aminoglycoside 6'-N-acetyltransferase type Ib to amikacin resistance // mSphere. 2024. V. 9. № 3. https://doi.org/10.1128/msphere.00789-23
  16. Peterson E., Kaur P. Antibiotic resistance mechanisms in bacteria: Relationships between resistance determinants of antibiotic producers, environmental bacteria, and clinical pathogens // Front. Microbiol. 2018. V. 9. https://doi.org/10.3389/fmicb.2018.02928
  17. Hotta K. Basic and applied research on multiple aminoglycoside antibiotic resistance of actinomycetes: an old-timer's recollection // J. Ind. Microbiol. Biotechnol. 2021. V. 48. № 9–10. https://doi.org/10.1093/jimb/kuab059
  18. Nesme J., Simonet P. The soil resistome: A critical review on antibiotic resistance origins, ecology and dissemination potential in telluric bacteria // Environ Microbiol. 2015. V. 17. № 4. P. 913–930. https://doi.org/10.1111/1462-2920.12631
  19. Alekseeva M.G., Rudakova N.N., Ratkin A.V. et al. Resistome in Streptomyces rimosus – a reservoir of aminoglycoside antibiotics resistance genes // Biochemistry (Moscow). 2023. V. 88. № 6. P. 723–730. https://doi.org/10.1134/S0006297923060019
  20. Altschul S.F., Madden T.L., Schaffer A.A. et al. Gapped BLAST and PSI-BLAST: A new generation of protein database search programs // Nucl. Ac. Res. 1997. V. 25. № 17. P. 3389–3402. https://doi.org/10.1093/nar/25.17.3389
  21. Tamura K., Stecher G., Kumar S. MEGA11: Molecular evolutionary genetics analysis version 11 // Mol. Biol. Evol. 2021. V. 38. № 7. P. 3022–3027. https://doi.org/10.1093/molbev/msab120
  22. Gil-Gil T., Laborda P., Sanz-García F. et al. Antimicrobial resistance: A multifaceted problem with multipronged solutions // Microbiologyopen. 2019. V. 8. № 11. https://doi.org/10.1002/mbo3.945
  23. Roohi R., Bano N. Actinobacteria: Smart micro-factories for the health sector // Recent. Pat. Biotechnol. 2024. May 10. https://doi.org/10.2174/0118722083300181240429072502. Epub ahead of print
  24. Niranjan V., Uttarkar A., Murali K. et al. Mycobacterium time-series genome analysis identifies aac2' as a potential drug target with naloxone showing potential bait drug synergism // Molecules. 2022. V. 27. № 19. https://doi.org/10.3390/molecules27196150
  25. Shin D.M., Jeon B.Y., Lee H.M. et al. Mycobacterium tuberculosis eis regulates autophagy, inflammation, and cell death through redox-dependent signaling // PLoS Pathog. 2010. V. 6. № 12. https://doi.org/10.1371/journal.ppat.1001230
  26. Duan L., Yi M., Chen J. et al. Mycobacterium tuberculosis EIS gene inhibits macrophage autophagy through up-regulation of IL-10 by increasing the acetylation of histone H3 // Biochem. Biophys. Res. Commun. 2016. V. 473. № 4. P. 1229–1234. https://doi.org/10.1016/j.bbrc.2016.04.045
  27. Ватлин А.А., Беккер О.Б., Лысенкова Л.Н. и др. Секвенирование и анализ резистома Streptomyces fradiae ATCC19609 с целью разработки тест-системы для скрининга новых антибактериальных веществ // ГЕНЕТИКА. 2016. Т. 52. № 6. С. 723–727.
  28. Kovtun A.S., Averina O.V., Alekseeva M.G. et al. Antibiotic resistance genes in the gut microbiota of children with autistic spectrum disorder as possible predictors of the disease // Microb. Drug. Resist. 2020. V. 26. № 11. P. 1307–1320. https://doi.org/10.1089/mdr.2019.0325

Supplementary files

Supplementary Files
Action
1. JATS XML
Download
2. Fig. 1. Phylogenetic tree constructed based on the amino acid sequences of AAC(2') strains producing AG, producers of other classes, and previously identified AAC(2')-I enzymes.

Download (131KB)
Indexing metadata
3. Fig. 2. Phylogenetic tree constructed based on the alignment of amino acid sequences of Eis acetyltransferases from AG producers with Eis from M. tuberculosis.

Download (344KB)
Indexing metadata

Copyright (c) 2025 Russian Academy of Sciences