Mikrobiol. Z. 2022; 84(3):60-68.
doi: https://doi.org/10.15407/microbiolj84.03.060

Resistance to Tetracycline and Oleandomycin of a Number of Streptomycetes —
Producers of Polyketide Antibiotics

L.V. Polishchuk, O.I. Bambura

Zabolotny Institute of Microbiology and Virology, NAS of Ukraine
154 Acad. Zabolotny Str., Kyiv, 03143, Ukraine

Recently, antibiotic resistance of pathogenic and opportunistic microorganisms is one of the primary problems of medicine. Scientists pay considerable attention to the study of genes for resistance of strains of streptomycetes as sources of such genes for microorganisms. The aim of this study was to determine the sensitivity of 9 strains of streptomycetes producing polyketide antibiotics to tetracycline and oleandomycin and to identify possible correlations in resistant and sensitive strains between the level of their resistance and the presence of resistance genes in chromosomes. Methods. 9 strains of producers of polyketide antibiotics were studied: Streptomyces cyanogenus S136, S. fradiae Tu2717, S. glaucescens Tu49, S. olivaceus Tu2353, S. antibioticus 35, S. globisporus 1912, S. aureofaciens 019, S. coelicolor A3(2), S. lividans TK24. Appropriate microbiological (method of serial dilution in agar) and biotechnological (method of computerized analysis of sequences) methods were used. Results. According to the sensitivity to oleandomycin and tetracycline, the studied strains of streptomycetes can be divided into 3 groups. The first group includes strains resistant to both antibiotics — S. coelicolor A3(2) and S. lividans TK24, the second group includes strains resistant to only one of the antibiotics: more resistant to oleandomycin — S. globisporus 1912, S. glaucescens Tu49, S antibiotic 35-1; more resistant to tetracycline — S. olivaceus Tu2353, S. fradiae Tu2717, S. aureofaciens 019. Strain S. cyanogenus S136 is sensitive to both antibiotics. Conclusions. A correlation was found between the level of tetracycline resistance and the presence (the number and similarity of structures) in the genomes of strains S. lividans TK24, S. globisporus 1912, and S. cyanogenus S136 sequences, which are similar to the sequences of tetracycline resistance genes of strain S. coelicolor A3(2).

Keywords: antibiotic, resistance, Streptomyces, gene.

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  1. Wencewicz TA. Crossroads of Antibiotic Resistance and Biosynthesis. J Mol Biol. 2019; 431(18):3370—3399. https://doi.org/10.1016/j.jmb.2019.06.033
  2. Trenin AS. [Methodology of screening new antibiotics: present status and prospects]. Antibiotics and chemotherapy. 2015; 60(7—8):34—46. Russian.
  3. Jian Z, Zeng L, Xu T, Sun S, et al. Antibiotic resistance genes in bacteria: Occurrence, spread, and control. J Basic Microbiol. 2021; 61(12):1049—1070. https://doi.org/10.1002/jobm.202100201
  4. Rebets Y, Ostash B, Gromyko O, et al. Resistance of recombinant Streptomyces albus cest 114 and Streptomyces globisporus strains to landomycins E. Visnyk of L’viv univ. Biology Series. 2003; 33:47—54.
  5. Chen J, Wu Q, Hawas UW, Wang H. Genetic regulation and manipulation for natural product discovery. Appl Microbiol Biotechnol. 2016; 100(7):2953—2965. https://doi.org/10.1007/s00253-016-7357-3
  6. Lewis RL, Laing E, Allenby N, et al. Metabolic and evolutionary insights into the closely-related species Streptomyces coelicolor and Streptomyces lividans deduced from high-resolution comparative genomic hybridization. BMC Genomics. 2010; 1(11):682—698. https://doi.org/10.1186/1471-2164-11-682
  7. Gromyko O, Basiliya L, Kirichenko N, et al. Obtaining and characteristics of streptomycin resistant mutants of antitumor landomycin E producer Streptomyces globisporus 3-1. Visn Lviv Univ Ser Biol. 2000; 26(1):46—53.
  8. Lee LF, Chen YJ, Kirby R, et al. A multidrug efflux system is involved in colony growth in Streptomyces lividans. Microbiology (Reading). 2007; 153 (Pt 4):924—934.
  9. Vecchione JJ, Alexander B, Sello JK. Two distinct major facilitator superfamily drug efflux pumps mediate chloramphenicol resistance in Streptomyces coelicolor. Antimicrobial agents and chemotherapy. 2009; 53(11):4673—4677. https://doi.org/10.1128/AAC.00853-09
  10. Nag A, Mehraa S. A Major Facilitator Superfamily (MFS) efflux pump, SCO4121, from Streptomyces coelicolor with roles in multidrug resistance and oxidative stress tolerance and its regulation by a MarR regulator. Applied and Environmental Microbiology. 2001; 87(7):2238—2250. https://doi.org/10.1128/AEM.02238-20
  11. Dubinska L, Zavorotna S, Ostash B, et al. Characteristics of resistance of patterns to antibiotics of producers of antitumor antibiotics Streptomyces globisporus 1912, Streptomyces peucetius ATCC 29050 and Streptomyces peucetius supsp. caesius ATCC 27952. Visnyk Lviv Univ Ser. Biology. 2000; 25910:49—56.
  12. Tymchik OV, Matselyukh BP, Lavrinchuk VYa. [Sensitivity of Streptomyces globisporus 3-1 — a highly active producer of landomycin E — to its own and other polyketide antibiotics]. Mikrobiol Z. 2004: 66(2):69—73. Ukrainian.
  13. Matseliukh BP, Konovalova TA, Polishchuk LV, et al. [Sensitivity of streptomycetes, producers of polyketide antibiotics, to landomycins A and E]. Mikrobiol Z. 1998; 60(1):31—36. Ukrainian.
  14. Vinogradova KA, Bulgakova VG, Polin AN, et al. [Streptomycetes Biofilms. I. Occurrence and Formation]. Antibiotics and Chemotherapy. 2015; 60(1—2):39—46. Russian.
  15. Ogawara H. Comparison of Antibiotic Resistance Mechanisms in Antibiotic- Producing and Pathogenic Bacteria. Molecules. 2019; 24(19):3430. https://doi.org/10.3390/molecules24193430
  16. Zhang J, Duan Y, Zhu X, Yan X. [Novel angucycline/angucyclinone family of natural products discovered between 2010 and 2020]. Chinese journal of biotechnolog. 2021; 37(6):2147—2165. Chinese.
  17. Lazar G, Zahner H, Breiding S, et al. 3-Demethoxy-3-ethoxy-tetracenomycin C. J Antibiot (Tokyo). 1981; 34(8):1067—1068. https://doi.org/10.7164/antibiotics.34.1067
  18. Decker H, Rohr J, Motamedi H, et al. Identification of Streptomyces olivaceus Tu 2353 genes involved in the production of the polyketide elloramycin. Gene. 1995; 166(1):121—6. https://doi.org/10.1016/0378-1119(95)00573-7
  19. Lavrinchuk VJa, Stryzhkova HM, Matseliukh BP. [The induction of mutations in Streptomyces aureofaciens by UV rays and nitrosoguanidine and the identification of the mutants obtained]. Mikrobiol Z. 1997; 59(2):20—24. Ukrainian.
  20. Hopwood DA, Chater KF, Bibb MJ. Genetics of antibiotic production in Streptomyces coelicolor A3(2), a model streptomycete. Biotechnology. 1995; 28:65—102. https://doi.org/10.1016/B978-0-7506-9095-9.50009-5