Browsing by Author "Mira, Ana Rita"
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- Drug resistance and epigenetic modulatory potential of epigallocatechin-3-gallate against Staphylococcus aureusPublication . Zeferino, Ana Sofia; Mira, Ana Rita; Delgadinho, Mariana; Brito, Miguel; Ponte, Tomás; Ribeiro, EdnaAntimicrobial resistance of human pathogens, such as methicillin-resistant Staphylococcus aureus, is described by the World Health Organization as a health global challenge and efforts must be made for the discovery of new effective and safe compounds. This work aims to evaluate epigallocatechin-3-gallate (EGCG) epigenetic and modulatory drug potential against S. aureus in vitro and in vivo. S. aureus strains were isolated from the commensal flora of healthy volunteers. Antibiotic susceptibility and synergistic assay were assessed through disk diffusion accordingly to EUCAST guidelines with and without co-exposure to EGCG at final concentrations of 250 µg/ml, 100 µg/ml, 50 µg/ml, and 25 µg/ml. Transcriptional expression of orfx, spdC, and WalKR was performed through qRT-PCR. A 90-day interventional study was performed with daily consumption of 225 mg of EGCG. Obtained data revealed a high prevalence of S. aureus colonization in healthcare workers and clearly demonstrated the antimicrobial and synergistic potential of EGCG as well as divergent resistant phenotypes associated with altered transcriptional expression of epigenetic and drug response modulators genes. Here, we demonstrate the potential of EGCG for antimicrobial treatment and/or therapeutic adjuvant against antibiotic-resistant microorganisms and report divergent patterns of epigenetic modulators expression associated with phenotypic resistance profiles.
- Efeito modulador da EGCG na transcrição de genes de virulência em Staphylococcus aureus com perfis fenotípicos de resistência divergentesPublication . Ribeiro, Edna; Santos, Raquel; Almeida, Raquel; Delgadinho, Mariana; Mira, Ana Rita; Zeferino, Ana SofiaIntrodução: A resistência de patógenos humanos a múltiplos antibióticos é considerada pela Organização Mundial de Saúde uma ameaça global à saúde humana. Nos últimos anos, vários grupos de investigação têm investido na descoberta de novas moléculas com potencial antimicrobiano para utilização em terapêutica e/ou como adjuvante terapêutico. Um dos microrganismos de interesse, com resistência associada, é o Staphylococcus aureus resistente à meticilina (MRSA). Estirpes de MRSA têm diferenças significativas a nível de fatores de risco, resistência a antibióticos, taxa de crescimento, toxinas e/ou fatores de virulência. A Epigalocatequina-3-galato (EGCG), a principal catequina constituinte do chá verde, tem sido descrita como eficaz na reversão do fenótipo de resistência no MRSA, demonstrando ter um efeito sinérgico contra diferentes antibióticos, incluindo B-lactâmicos, como amoxicilina e imipenem, capazes de interferir na síntese da parede celular bacteriana e tetraciclina e gentamicina, classificados como antibióticos inibidores da síntese de proteínas. Objetivos: Neste estudo pretende-se avaliar o potencial da EGCG na modulação da expressão génica associada a genes de virulência (atividade hemolítica), nomeadamente hlgA, hly e hlgB, em estirpes de MRSA com divergências fenotípicas associadas à resistência antimicrobiana, incluindo reversão do fenótipo de resistência.
- Epigenetic and drug response modulation of epigalocaten-in-3-gallate in staphylococcus aureus with divergent resistance phenotypesPublication . Mira, Ana Rita; Zeferino, Ana Sofia; Inácio, Raquel; Delgadinho, Mariana; Brito, Miguel; Calado, Cecília; Ribeiro, EdnaHealthcare-associated methicillin-resistant Staphylococcus aureus 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 S. aureus strains with divergent resistance phenotypes. EGCG exposure effects in epigenetic and drug resistance key modulators were also evaluated. S. aureus strains (n = 32) were isolated from infected patients in a Lisbon hospital. The identification of the S. aureus 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 OrfX, SpdC and WalKR 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 OrfX, particularly in MRSA strains, as well as the key drug response modulators SpdC and WalKR. 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.
- Epigenetic and drug response modulation of Epigalocaten-in-3-gallate in Staphylococcus aureus with divergent resistance phenotypesPublication . Mira, Ana Rita; Zeferino, Ana Sofia; Inácio, Raquel; Delgadinho, Mariana; Brito, Miguel; Calado, Cecília R. C.; Ribeiro, EdnaHealthcare-associated methicillin-resistant Staphylococcus aureus 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 S. aureus strains with divergent resistance phenotypes. EGCG exposure effects in epigenetic and drug resistance key modulators were also evaluated. S. aureus strains (n = 32) were isolated from infected patients in a Lisbon hospital. The identification of the S. aureus 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 OrfX, SpdC, and WalKR 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 OrfX, particularly in MRSA strains, as well as the key drug response modulators SpdC and WalKR. 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.