Effect of adamantane derivative on expression of biofilm-associated genes in methicillin-resistant Staphylococcus aureus
In the etiology of nosocomial infections, the leading role belongs to such microorganisms as Staphylococcus aureus. Insufficient effectiveness of antimicrobial chemotherapy and practical absence of drugs with an antibiofilm activity encourage the development of new remedies. The study presents resul...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-06-01
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| Series: | Medicine in Drug Discovery |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2590098623000052 |
| _version_ | 1797796111446966272 |
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| author | Nataliia Humeniuk Liubov Zelena Nina Vrynchanu Liudmyla Ishchenko Tetiana Bukhtiarova Yurii Korotkij Elena Vazhnichaya |
| author_facet | Nataliia Humeniuk Liubov Zelena Nina Vrynchanu Liudmyla Ishchenko Tetiana Bukhtiarova Yurii Korotkij Elena Vazhnichaya |
| author_sort | Nataliia Humeniuk |
| collection | DOAJ |
| description | In the etiology of nosocomial infections, the leading role belongs to such microorganisms as Staphylococcus aureus. Insufficient effectiveness of antimicrobial chemotherapy and practical absence of drugs with an antibiofilm activity encourage the development of new remedies. The study presents results on antibiofilm activity of the adamantane derivative 1-[4-(1-adamantyl)phenoxy]-3-(N-benzyl,N-dimethylamino)-2-propanol chloride (KVM-97) against methicillin-resistant S. aureus (MRSA) and the effect of this agent on the expression genes that provide regulatory and biosynthetic functions of biofilms. The ability of adamantane derivative to affect S. aureus biofilms was tested by microtiter dish biofilm formation assay. The effect of KVM-97 on expression level of genes icaA, icaD, icaR, agrA, sarA, clfB, fib, fnbB, ebpS, and eno was detected by the real-time PCR. The KVM-97 inhibits the formation of S. aureus biofilms at 5.0 MIC by 95.1 % and at 0.5 MIC – by 22.4 %. Under the action of KVM-97, destruction of the mature biofilms was not detected. It inhibits expression of the icaADBC operon and agrA gene, as well as stimulates a transcriptional activity of the icaR regulator. Subinhibitory concentrations of the KVM-97 significantly inhibit the expression of clfB, fib, fnbB, ebpS, and eno, but does not change the sarA gene expression. Thus, 1-[4-(1-adamantyl)phenoxy]-3-(N-benzyl,N-dimethylamino)-2-propanol chloride shows pronounced antibiofilm activity against MRSA at the early stages of the biofilm forming. This effect may be relating to influence on the expression of genes that regulate adhesion to the substrate and formation of S. aureus biofilms. |
| first_indexed | 2024-03-13T03:28:15Z |
| format | Article |
| id | doaj.art-4e776d6c87ce4faabb0f63e575f36cc5 |
| institution | Directory Open Access Journal |
| issn | 2590-0986 |
| language | English |
| last_indexed | 2024-03-13T03:28:15Z |
| publishDate | 2023-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Medicine in Drug Discovery |
| spelling | doaj.art-4e776d6c87ce4faabb0f63e575f36cc52023-06-25T04:43:30ZengElsevierMedicine in Drug Discovery2590-09862023-06-0118100155Effect of adamantane derivative on expression of biofilm-associated genes in methicillin-resistant Staphylococcus aureusNataliia Humeniuk0Liubov Zelena1Nina Vrynchanu2Liudmyla Ishchenko3Tetiana Bukhtiarova4Yurii Korotkij5Elena Vazhnichaya6State Institution ”Institute of Pharmacology and Toxicology of the National Academy of Medical Sciences of Ukraine”, 14, Antona Tsedika Str., Kyiv 03057, Ukraine; Corresponding author at: State Institution “Institute of Pharmacology and Toxicology of the National Academy of Medical Sciences of Ukraine”, 14, Antona Tsedika Str., Kyiv 03057, Ukraine.Zabolotny Institute of Microbiology and Virology of the National Academy of Sciences of Ukraine, 154, Akademika Zabolotnogo Str., Kyiv 03143, UkraineState Institution ”Institute of Pharmacology and Toxicology of the National Academy of Medical Sciences of Ukraine”, 14, Antona Tsedika Str., Kyiv 03057, UkraineUkrainian Laboratory of Quality and Safety of Agricultural Products, the National University of Life and Environmental Sciences of Ukraine of the National Academy of Agrarian Sciences of Ukraine, 7, Mashynobudivnykiv Str., Chabany, Kyiv Oblast 08162, UkraineState Institution ”Institute of Pharmacology and Toxicology of the National Academy of Medical Sciences of Ukraine”, 14, Antona Tsedika Str., Kyiv 03057, UkraineInstitute of Organic chemistry of the National Academy of Sciences of Ukraine, 5, Murmanska Str., Kyiv 02660, UkrainePoltava State Medical University, 23, Shevchenka Str., Poltava 36011, UkraineIn the etiology of nosocomial infections, the leading role belongs to such microorganisms as Staphylococcus aureus. Insufficient effectiveness of antimicrobial chemotherapy and practical absence of drugs with an antibiofilm activity encourage the development of new remedies. The study presents results on antibiofilm activity of the adamantane derivative 1-[4-(1-adamantyl)phenoxy]-3-(N-benzyl,N-dimethylamino)-2-propanol chloride (KVM-97) against methicillin-resistant S. aureus (MRSA) and the effect of this agent on the expression genes that provide regulatory and biosynthetic functions of biofilms. The ability of adamantane derivative to affect S. aureus biofilms was tested by microtiter dish biofilm formation assay. The effect of KVM-97 on expression level of genes icaA, icaD, icaR, agrA, sarA, clfB, fib, fnbB, ebpS, and eno was detected by the real-time PCR. The KVM-97 inhibits the formation of S. aureus biofilms at 5.0 MIC by 95.1 % and at 0.5 MIC – by 22.4 %. Under the action of KVM-97, destruction of the mature biofilms was not detected. It inhibits expression of the icaADBC operon and agrA gene, as well as stimulates a transcriptional activity of the icaR regulator. Subinhibitory concentrations of the KVM-97 significantly inhibit the expression of clfB, fib, fnbB, ebpS, and eno, but does not change the sarA gene expression. Thus, 1-[4-(1-adamantyl)phenoxy]-3-(N-benzyl,N-dimethylamino)-2-propanol chloride shows pronounced antibiofilm activity against MRSA at the early stages of the biofilm forming. This effect may be relating to influence on the expression of genes that regulate adhesion to the substrate and formation of S. aureus biofilms.http://www.sciencedirect.com/science/article/pii/S2590098623000052Adamantane derivativeMethicillin-resistant Staphylococcus aureusGene expressionBiofilmAdhesion |
| spellingShingle | Nataliia Humeniuk Liubov Zelena Nina Vrynchanu Liudmyla Ishchenko Tetiana Bukhtiarova Yurii Korotkij Elena Vazhnichaya Effect of adamantane derivative on expression of biofilm-associated genes in methicillin-resistant Staphylococcus aureus Medicine in Drug Discovery Adamantane derivative Methicillin-resistant Staphylococcus aureus Gene expression Biofilm Adhesion |
| title | Effect of adamantane derivative on expression of biofilm-associated genes in methicillin-resistant Staphylococcus aureus |
| title_full | Effect of adamantane derivative on expression of biofilm-associated genes in methicillin-resistant Staphylococcus aureus |
| title_fullStr | Effect of adamantane derivative on expression of biofilm-associated genes in methicillin-resistant Staphylococcus aureus |
| title_full_unstemmed | Effect of adamantane derivative on expression of biofilm-associated genes in methicillin-resistant Staphylococcus aureus |
| title_short | Effect of adamantane derivative on expression of biofilm-associated genes in methicillin-resistant Staphylococcus aureus |
| title_sort | effect of adamantane derivative on expression of biofilm associated genes in methicillin resistant staphylococcus aureus |
| topic | Adamantane derivative Methicillin-resistant Staphylococcus aureus Gene expression Biofilm Adhesion |
| url | http://www.sciencedirect.com/science/article/pii/S2590098623000052 |
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