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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Main Authors: Ana Rita Mira, Ana Sofia Zeferino, Raquel Inácio, Mariana Delgadinho, Miguel Brito, Cecília R. C. Calado, Edna Ribeiro
Format: Article
Language:English
Published: MDPI AG 2023-03-01
Series:Antibiotics
Subjects:
Online Access:https://www.mdpi.com/2079-6382/12/3/519
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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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