Epigenetic and Drug Response Modulation of Epigalocaten-In-3-Gallate in <i>Staphylococcus aureus</i> with Divergent Resistance Phenotypes
Healthcare-associated methicillin-resistant <i>Staphylococcus aureus</i> infections represent extremely high morbidity and mortality rates worldwide. We aimed to assess the antimicrobial potential and synergistic effect between Epigalocatenin-3-gallate (EGCG) and different antibiotics in...
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MDPI AG
2023-03-01
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author | Ana Rita Mira Ana Sofia Zeferino Raquel Inácio Mariana Delgadinho Miguel Brito Cecília R. C. Calado Edna Ribeiro |
author_facet | Ana Rita Mira Ana Sofia Zeferino Raquel Inácio Mariana Delgadinho Miguel Brito Cecília R. C. Calado Edna Ribeiro |
author_sort | Ana Rita Mira |
collection | DOAJ |
description | Healthcare-associated methicillin-resistant <i>Staphylococcus aureus</i> infections represent extremely high morbidity and mortality rates worldwide. We aimed to assess the antimicrobial potential and synergistic effect between Epigalocatenin-3-gallate (EGCG) and different antibiotics in <i>S. aureus</i> strains with divergent resistance phenotypes. EGCG exposure effects in epigenetic and drug resistance key modulators were also evaluated. <i>S. aureus</i> strains (<i>n</i> = 32) were isolated from infected patients in a Lisbon hospital. The identification of the <i>S. aureus</i> resistance phenotype was performed through automatized methods. The antibiotic synergistic assay was performed through disk diffusion according to EUCAST guidelines with co-exposure to EGCG (250, 100, 50 and 25 µg/mL). The bacteria’s molecular profile was assessed through FTIR spectroscopy. The transcriptional expression of <i>OrfX</i>, <i>SpdC</i> and <i>WalKR</i> was performed by using qRT-PCR. FTIR-spectroscopy analysis enabled the clear discrimination of MRSA/MSSA strains and the EGCG exposure effect in the bacteria’s molecular profiles. Divergent resistant phenotypes were associated with divergent transcriptional expression of the epigenetic modulator <i>OrfX</i>, particularly in MRSA strains, as well as the key drug response modulators <i>SpdC</i> and <i>WalKR</i>. These results clearly demonstrate that EGCG exposure alters the expression patterns of key epigenetic and drug response genes with associated divergent-resistant profiles, which supports its potential for antimicrobial treatment and/or therapeutic adjuvant against antibiotic-resistant microorganisms. |
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spelling | doaj.art-262c41a695b44694b54855e84cac67e72023-11-17T09:14:09ZengMDPI AGAntibiotics2079-63822023-03-0112351910.3390/antibiotics12030519Epigenetic and Drug Response Modulation of Epigalocaten-In-3-Gallate in <i>Staphylococcus aureus</i> with Divergent Resistance PhenotypesAna Rita Mira0Ana Sofia Zeferino1Raquel Inácio2Mariana Delgadinho3Miguel Brito4Cecília R. C. Calado5Edna Ribeiro6H&TRC—Health & Technology Research Center, ESTeSL—Escola Superior de Tecnologia da Saúde, Instituto Politécnico de Lisboa, Av. D. João II, lote 4.69.01, Parque das Nações, 1990-096 Lisboa, PortugalEscola Superior de Tecnologia da Saúde, Instituto Politécnico de Lisboa, Av. D. João II, lote 4.69.01, Parque das Nações, 1990-096 Lisboa, PortugalCIMOSM—Centro de Investigação em Modelação e Otimização de Sistemas Multifuncionais, ISEL—Instituto Superior de Engenharia de Lisboa, Instituto, Politécnico de Lisboa, R. Conselheiro Emidio Navarro 1, 1959-007 Lisboa, PortugalH&TRC—Health & Technology Research Center, ESTeSL—Escola Superior de Tecnologia da Saúde, Instituto Politécnico de Lisboa, Av. D. João II, lote 4.69.01, Parque das Nações, 1990-096 Lisboa, PortugalH&TRC—Health & Technology Research Center, ESTeSL—Escola Superior de Tecnologia da Saúde, Instituto Politécnico de Lisboa, Av. D. João II, lote 4.69.01, Parque das Nações, 1990-096 Lisboa, PortugalCIMOSM—Centro de Investigação em Modelação e Otimização de Sistemas Multifuncionais, ISEL—Instituto Superior de Engenharia de Lisboa, Instituto, Politécnico de Lisboa, R. Conselheiro Emidio Navarro 1, 1959-007 Lisboa, PortugalH&TRC—Health & Technology Research Center, ESTeSL—Escola Superior de Tecnologia da Saúde, Instituto Politécnico de Lisboa, Av. D. João II, lote 4.69.01, Parque das Nações, 1990-096 Lisboa, PortugalHealthcare-associated methicillin-resistant <i>Staphylococcus aureus</i> infections represent extremely high morbidity and mortality rates worldwide. We aimed to assess the antimicrobial potential and synergistic effect between Epigalocatenin-3-gallate (EGCG) and different antibiotics in <i>S. aureus</i> strains with divergent resistance phenotypes. EGCG exposure effects in epigenetic and drug resistance key modulators were also evaluated. <i>S. aureus</i> strains (<i>n</i> = 32) were isolated from infected patients in a Lisbon hospital. The identification of the <i>S. aureus</i> resistance phenotype was performed through automatized methods. The antibiotic synergistic assay was performed through disk diffusion according to EUCAST guidelines with co-exposure to EGCG (250, 100, 50 and 25 µg/mL). The bacteria’s molecular profile was assessed through FTIR spectroscopy. The transcriptional expression of <i>OrfX</i>, <i>SpdC</i> and <i>WalKR</i> was performed by using qRT-PCR. FTIR-spectroscopy analysis enabled the clear discrimination of MRSA/MSSA strains and the EGCG exposure effect in the bacteria’s molecular profiles. Divergent resistant phenotypes were associated with divergent transcriptional expression of the epigenetic modulator <i>OrfX</i>, particularly in MRSA strains, as well as the key drug response modulators <i>SpdC</i> and <i>WalKR</i>. These results clearly demonstrate that EGCG exposure alters the expression patterns of key epigenetic and drug response genes with associated divergent-resistant profiles, which supports its potential for antimicrobial treatment and/or therapeutic adjuvant against antibiotic-resistant microorganisms.https://www.mdpi.com/2079-6382/12/3/519healthcare-associated <i>S. aureus</i> infectionsepigallocatechin-3-gallate (EGCG)synergistic effectsdrug resistance phenotypesepigenetic modulatordrug resistance modulators |
spellingShingle | Ana Rita Mira Ana Sofia Zeferino Raquel Inácio Mariana Delgadinho Miguel Brito Cecília R. C. Calado Edna Ribeiro Epigenetic and Drug Response Modulation of Epigalocaten-In-3-Gallate in <i>Staphylococcus aureus</i> with Divergent Resistance Phenotypes Antibiotics healthcare-associated <i>S. aureus</i> infections epigallocatechin-3-gallate (EGCG) synergistic effects drug resistance phenotypes epigenetic modulator drug resistance modulators |
title | Epigenetic and Drug Response Modulation of Epigalocaten-In-3-Gallate in <i>Staphylococcus aureus</i> with Divergent Resistance Phenotypes |
title_full | Epigenetic and Drug Response Modulation of Epigalocaten-In-3-Gallate in <i>Staphylococcus aureus</i> with Divergent Resistance Phenotypes |
title_fullStr | Epigenetic and Drug Response Modulation of Epigalocaten-In-3-Gallate in <i>Staphylococcus aureus</i> with Divergent Resistance Phenotypes |
title_full_unstemmed | Epigenetic and Drug Response Modulation of Epigalocaten-In-3-Gallate in <i>Staphylococcus aureus</i> with Divergent Resistance Phenotypes |
title_short | Epigenetic and Drug Response Modulation of Epigalocaten-In-3-Gallate in <i>Staphylococcus aureus</i> with Divergent Resistance Phenotypes |
title_sort | epigenetic and drug response modulation of epigalocaten in 3 gallate in i staphylococcus aureus i with divergent resistance phenotypes |
topic | healthcare-associated <i>S. aureus</i> infections epigallocatechin-3-gallate (EGCG) synergistic effects drug resistance phenotypes epigenetic modulator drug resistance modulators |
url | https://www.mdpi.com/2079-6382/12/3/519 |
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