Investigation of the complex antibiotic INA-5812

Lapchinskaya, Olda A.; Катруха, Г. С.; Gladkikh, Elena G.; Kulyaeva, V. V.; Coodan, P. V.; Topolyan, A. P.; Alferova, Vera A.; Pogozheva, V. V.; Sukonnikov, M. A.; Рогожин, Е. А.; Prokhorenko, Igor A.; Brylev, Vladimir A.; Королев, А. М.; Slyundina, M. S.; Борисов, Р. С.; Serebryakova, Marina V.; Shuvalov, Maxim V.; Ksenofontov, Alexander L.; Stoyanova, L. G.; Osterman, Ilya А.; Formanovsky, A. A.; Tashlitsky, Vadim N.; Baratova, Ludmila A.; Тимофеева, А. В.; Tyurin, Anton P.

doi:10.1134/s1068162016060078

Cited by 14 publications

(22 citation statements)

References 12 publications

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“…Due to these structural similarities, the new antibiotic INA 5812-A/C is believed to be an analog of vancomycin and daptomycin. However, preliminary investigation of antimicrobial spectra showed the activity of 5812-A/C against Gram-negative P. vulgaris (Lapchinskaya et al, 2016), which differed from both vancomycin and daptomycin. In this regard, it is obvious that the mechanism of action of the new antibiotic is also presumably different from its analogs.…”

Section: Discussionmentioning

confidence: 99%

“…In this study, we performed a structural and functional analysis of the antimicrobial peptide complex 5812-A/C produced by S. roseoflavus INA-Ac-5812 ( Lapchinskaya et al, 2016 ). The peptide compound had strong bactericidal effect against Gram-positive bacteria.…”

Section: Discussionmentioning

confidence: 99%

“…The structural properties of the molecule were also investigated, and the exact molar mass, relative amino acid composition, and UV and fluorescence spectra were determined. Regarding structural elicitation, this compound was studied to determine an exact molecular mass, relative amino acid composition, UV and fluorescence spectra, and chemical derivatization ( Lapchinskaya et al, 2016 ), which is earlier used for modification of some aminoglycoside antibiotics ( Topolyan et al, 2016 ). At present, automated Edman degradation allowed for the determination of a partial structure of 5812-A/C, including a five amino acid fragment.…”

Section: Discussionmentioning

confidence: 99%

“…The novel antibiotic compound studied was firstly purified from a culture medium of actinomycete Streptomyces sp. INA-5812 (Gause Institute of New Antibiotics collection) and partially characterized and designated as 5812-A/C (5812-1; Lapchinskaya et al, 2016 ). The substance is presumably a cyclic (lipo)glycopeptide, with a molecular weight of 1,916.8 Da.…”

Section: Introductionmentioning

confidence: 99%

“…Interestingly, the first evaluation of the 5812-A/C antimicrobial spectra revealed the inhibition of the growth of some Gram-negative bacteria ( Prtoteus vulgaris 206) ( Lapchinskaya et al, 2016 ).…”

Section: Introductionmentioning

confidence: 99%

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A Novel Peptide Antibiotic Produced by Streptomyces roseoflavus Strain INA-Ac-5812 With Directed Activity Against Gram-Positive Bacteria

et al. 2020

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In this work, we report the isolation and detailed functional characterization for the new non-ribosomally synthesized antibiotic 5812-A/C, which was derived from metabolites of Streptomyces roseoflavus INA-Ac-5812. According to its chemical structure, the studied 5812-A/C preliminary is composed of a cyclic peptide part covalently bounded with an arabinose residue. N-terminal amino acid sequencing of the native peptide has identified its partial structure of Leu-Asp-Gly-Ser-Gly and consisting of a Tyr residue that is supposed to have a two-component peptide nature for the molecule studied. However, the structural analysis of the antibiotic complex derived from S. roseoflavus INA-Ac-5812 is still ongoing. The mechanism of action of 5812-A/C was assessed in comparison with its most related analog, the lipopeptide antibiotic daptomycin, given the presence in both antimicrobials of an L-kynurenine amino acid residue. The inhibitory activity of 5812-A/C against Gram-positive bacteria including methicillin-resistant strain of Staphylococcus aureus was similar to daptomycin. The mechanism of action of 5812-A/C was associated with the disruption of membrane integrity, which differs in comparison with daptomycin and is most similar to the antimicrobial membranedisturbing peptides. However, 5812-A/C demonstrated a calcium-dependent mode of action. In addition, unlike daptomycin, 5812-A/C was able to penetrate mature biofilms and inhibit the metabolic activity of embedded S. aureus cells. At the same time, 5812-A/C has no hemolytic activity toward erythrocyte, but possessed weak cytotoxic activity represented by heterochromatin condensation in human buccal epithelium cells. The biological properties of the peptide 5812-A/C suggest its classification as a calcium-dependent antibiotic effective against a wide spectrum of Gram-positive pathogenic bacteria.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A Novel Peptide Antibiotic Produced by Streptomyces roseoflavus Strain INA-Ac-5812 With Directed Activity Against Gram-Positive Bacteria

et al. 2020

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Gausemycins A,B: Cyclic Lipoglycopeptides fromStreptomycessp.**

et al. 2021

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We report a novel family of natural lipoglycopeptides produced by Streptomyces sp. INA-Ac-5812. Two major components of the mixture, named gausemycins A and B, were isolated, and their structures were elucidated. The compounds are cyclic peptides with a unique peptide core and several remarkable structural features, including unusual positions of D-amino acids, lack of the Ca 2+ -binding Asp-X-Asp-Gly (DXDG) motif, tyrosine glycosylation with arabinose, presence of 2-amino-4-hydroxy-4-phenylbutyric acid (Ahpb) and chlorinated kynurenine (ClKyn), N-acylation of the ornithine side chain. These major components of the peptide antibiotic family have pronounced activity against Grampositive bacteria. The mechanism of action of gausemycins was explored by a number of methods, showing significant differences compared to glycopeptides and related lipopeptides. Gausemycins exhibit only slight Ca 2+ -dependence of antimicrobial activity and induce no pore formation at low concentrations. Moreover, there is no detectable accumulation of cell wall biosynthesis precursors under treatment with gausemycins.

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