Antimicrobial and Cytotoxic Characteristics of Antibiotic Streptofungin

Authors

DOI:

https://doi.org/10.20535/ibb.2023.7.2.286158

Keywords:

antimicrobial activity, cytotoxicity, antibiotics, pathogens, antimicrobial substances, streptomycetes

Abstract

Background. Streptomycetes were and remain a source of new antimicrobial compounds of various nature. A new wave of interest in such research is associated with the possibilities of applied genomics to reveal the hidden biosynthetic potential of streptomycetes, and therefore the discovery of new practically valuable antimicrobial products. The problem of antibiotic resistance of pathogens can be solved by creating compositions of active substances of different nature to overcome the protective mechanisms of pathogens.

Objective. The purpose of the work was to establish and evaluate the antimicrobial and cytotoxic characteristics of the new antibiotic streptofungin, synthesized by Streptomyces albus 2435 (CMIM-S-668) and its mutant strains 2435/М, UN44, 4S, US101, AE6, 105, 80/5.

Methods. To establish the characteristics of streptofungin, the antagonistic activity of selected S. albus producer strains was determined (by the radial streak method), the minimum inhibitory concentration of the antibiotic (by the serial dilution method), and cytotoxicity was determined by the MTT test with resazurin.

Results. The activity of the antibiotic streptofungin against Candida fungi (C. albicans, C. utilis) is shown. Minimum inhibitory concentrations of streptofungin were determined for C. albicans ATCC 10231 (10 μg/ml), B. subtilis ATCC 6633 (200 μg/ml) and P. aeruginosa ATCC 9027 (500 μg/ml). According to the resazurin test, streptofungin does not show a cytotoxic effect in a wide range of concentrations from 2.5 to 500 μg/ml, and therefore can be considered potentially permissible for humans and animals in the studied concentrations.

Conclusions. The antagonistic activity of mutant strains of S. albus culture is due to the action of a complex of antimicrobial products that have a different antimicrobial spectrum and mechanism of action. The obtained results give reasons to consider streptofungin as a promising pharmaceutical substance with antifungal action, as well as to consider the possibility of its combination with the bacteriolytic enzyme complex of the same culture for the development of an antimicrobial agent with a wide spectrum of action.

References

Tacconelli E, Carrara E, Savoldi A, Harbarth S, Mendelson M, Monnet DL, et al. Discovery, research, and development of new antibiotics: the WHO priority list of antibiotic-resistant bacteria and tuberculosis. Lancet Infect Dis. 2018;18(3):318-27. DOI: 10.1016/S1473-3099(17)30753-3

Park D, Swayambhu G, Lyga T, Pfeifer BA. Complex natural product production methods and options. Synth Syst Biotechnol. 2021;6(1):1-11. DOI: 10.1016/j.synbio.2020.12.001

Chen M, Cao Z, Tang W, Wang M, Chen Y, Guo Z. Discovery of novel septacidin congeners from a high yield heterologous expression strain Streptomyces albus 1597. J Antibiot (Tokyo). 2022;75(3):172-5. DOI: 10.1038/s41429-022-00499-6

Shemediuk AL, Dolia BS, Ochi K, Fedorenko VO, Ostash BO. Properties of spontaneous rpsL Mutant of Streptomyces albus KO-1297. Cytol Genet. 2022;56(1):31-6. DOI: 10.3103/S009545272201011X

Westhoff S, Otto SB, Swinkels A, Bode B, van Wezel GP, Rozen DE. Spatial structure increases the benefits of antibiotic production in Streptomyces. Evolution. 2020 Jan;74(1):179-87. DOI: 10.1111/evo.13817

Santos-Beneit F, Ceniceros A, Nikolaou A, Salas JA, Gutierrez-Merino J. Identification of antimicrobial compounds in two Streptomyces sp. strains isolated from beehives. Front Microbiol. 2022;13:742168. DOI: 10.3389/fmicb.2022.742168

Houssam MA. Biochemical studies on antibiotic production from Streptomyces sp.: Taxonomy, fermentation, isolation and biological properties. J Saudi Chem Soc. 2015;19(1):12-22. DOI: 10.1016/j.jscs.2011.12.011

Zaburannyi N, Rabyk M, Ostash B, Fedorenko V, Luzhetskyy A. Insights into naturally minimised Streptomyces albus J1074 genome. BMC Genomics. 2014 Feb 5;15(1):97. DOI: 10.1186/1471-2164-15-97

Tseduliak VM, Dolia B, Ostash I, Lopatniuk M, Busche T, Ochi K, et al. Mutations within gene XNR_2147 for TetR-like protein enhance lincomycin resistance and endogenous specialized metabolism of Streptomyces albus J1074. J Appl Genet. 2023;64(1):185-95. DOI: 10.1007/s13353-022-00738-4

Todosiichuk TS, Klochko VV, Zelena LB. Taxonomic analysis of the Streptomyces sp. 2435 strain, a producer of antimicrobial substances. Microbiol Z. 2014;76(1):3-8.

Todosiichuk TS, Shinkarenko LM, Hocker H. Study of the component composition and specificity of the lytic enzyme complex of Streptomyces recifensis var. lyticus IMB Ac-5001. Sci News NTUU KPI. 2004;4:138-43.

Todosiichuk TS., Klochko VV, Savchuk YI, Kobzysta OP. New antibiotic substances of the Streptomyces albus enzybiotic complex. Microbiol J. 2019;81(5):62-72. DOI: 10.15407/microbiolj81.05.062

Fanaei Pirlar R, Emaneini M, Beigverdi R, Banar M, van Leeuwen WB, Jabalameli F. Combinatorial effects of antibiotics and enzymes against dual-species Staphylococcus aureus and Pseudomonas aeruginosa biofilms in the wound-like medium. PLoS One. 2020;15(6):e0235093. DOI: 10.1371/journal.pone.0235093

Xu G, Zhao Y, Du L, Qian G, Liu F. Hfq regulates antibacterial antibiotic biosynthesis and extracellular lytic-enzyme production in Lysobacter enzymogenes OH11. Microb Biotechnol. 2015;8(3):499-509. doi: 10.1111/1751-7915.12246

Mayerhöfer TG, Pahlow S, Popp J. The Bouguer-Beer-Lambert law: Shining light on the obscure. Chemphyschem. 2020;21(18):2029-46. DOI: 10.1002/cphc.202000464

Ghasemi M, Turnbull T, Sebastian S, Kempson I. The MTT assay: Utility, limitations, pitfalls, and interpretation in bulk and single-cell analysis. Int J Mol Sci. 2021;22(23):12827. DOI: 10.3390/ijms222312827

Todosiichuk TS, Zelena LB, Klochko VV. Multistage selection of soil actinomycete Streptomyces albus as a producer of antimicrobial substances. Emirates J Food Agricult. 2015;27(3):250-7. DOI: 10.9755/ejfa.v27i3.18267

CLSI. 2005. Performance standards for antimicrobial susceptibility testing; Fifteenths informational supplement. Clinical and laboratory standards institute, Wayne, PA.

Levchyk N, Liubinska A, Todosiichuk T, Rakhmetov J, Diakova M. The development of biological product for plant growing on the basis of Streptomyces albus. Eureka Life Sci. 2016;(5):32-9. DOI: 10.21303/2504-5695.2016.00235

Khattab AI, Babiker EH, Saeed HA. Streptomyces: isolation, optimization of culture conditions and extraction of secondary metabolites. Int Curr Pharm J. 2016;5(3):27-32. DOI: 10.3329/icpj.v5i3.26695

Mohammad AQ. Streptogrisin B. In: Rawlings ND, Salvesen G, editors. Handbook of proteolytic enzymes. 3rd edition. Elsevier; 2013. pp. 2549-55. DOI: 10.1016/B978-0-12-382219-2.00565-2

Taneja N, Kaur H. Insights into newer antimicrobial agents against gram-negative bacteria. Microbiol Insights. 2016;9:9-19. DOI: 10.4137/MBI.S29459

Chen C, Chen X, Ren B, Guo H, Abdel-Mageed WM, Liu X, et al. Characterization of Streptomyces sp. LS462 with high productivity of echinomycin, a potent antituberculosis and synergistic antifungal antibiotic. J Ind Microbiol Biotechnol. 2021;48(9-10):kuab079. DOI: 10.1093/jimb/kuab079

Prosser GA, de Carvalho LPS. Kinetic mechanism and inhibition of Mycobacterium tuberculosis D-alanine:D-alanine ligase by the antibiotic D-cycloserine. FEBS J. 2013;280(4):1150-66. DOI: 10.1111/febs.12108

Bao J, He F, Li Y, Fang L, Wang K, Song J, et al. Cytotoxic antibiotic angucyclines and actinomycins from the Streptomyces sp. XZHG99T. J Antibiot (Tokyo). 2018;71(12):1018-1024. DOI: 10.1038/s41429-018-0096-1

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Published

2023-08-22

How to Cite

1.
Klochko V, Todosiichuk T, Lin W, Kobzysta O, Bobyr V. Antimicrobial and Cytotoxic Characteristics of Antibiotic Streptofungin. Innov Biosyst Bioeng [Internet]. 2023Aug.22 [cited 2024Oct.4];7(2):13-21. Available from: http://ibb.kpi.ua/article/view/286158

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