Antibiotherapy in association with Epigallocatechin-3 gallate (EGCG) is an effective alternative for infections caused by methicillin-resistant Staphylococcus aureus?
DOI:
https://doi.org/10.25758/set.730Palavras-chave:
EGCG, MRSA, Antibiotic resistance, Transcription modulation, HaemolysinsResumo
Antimicrobial resistance of human pathogens such as Methicillin-Resistant Staphylococcus aureus (MRSA), is globally defined as a major public health concern. Currently, several new therapeutic approaches are being developed with the aim find an alternative to treat these infections, including the use of natural compounds with epigenetic modulation potential such as green tea catechins. In green tea, Epigallocatechin-3 gallate (EGCG) is the most abundant and medically relevant catechin, with anti-inflammatory, antioxidant, anti-carcinogenic, and antimicrobial properties as well as synergistic effects reported for several antibiotics. The search for new therapeutic alternatives has led to the development of studies regarding the EGCG effect in S. aureus virulence factors and transcriptional modulation. Several studies, including from our research group, have demonstrated that EGCG exposure is able to affect the bacteria transcriptional pattern in numerous genes. Transcriptional effects were reported in genes implicated in toxin production, such as hly, which encodes for an alpha-haemolysin-precursor and hlgA, hlgB, the gamma haemolysin subunits A and B, respectively, in the epigenetic modulator orfx (a staphylococci methyltransferase) and in genes involved in resistance responses (spdC and WalKR). Moreover, increasing evidence has demonstrated potential correlations between epigenetic modulation and the expression of virulence factors including haemolysins. It is clear that EGCG should be considered as a new compound for antimicrobial treatment and/or therapeutic adjuvant against antibiotic-resistant microorganisms even in divergent phenotypic resistance strains.
Downloads
Referências
World Health Organization. Antimicrobial resistance [homepage]. WHO; 2021 Nov 17. Available from: https://www.who.int/news-room/fact-sheets/detail/antimicrobial-resistance
Ribeiro E. Human methicillin-resistant S. aureus (MRSA) colonization: a major public health concern? Saúde & Tecnologia. 2019;(22):5-7.
Parvez MA, Saha K, Rahman J, Munmun RA, Rahman MA, Dey SK, et al. Antibacterial activities of green tea crude extracts and synergistic effects of epigallocatechin gallate (EGCG) with gentamicin against MDR pathogens. Heliyon. 2019;5(7):e02126.
Smith DL, Harris AD, Johnson JA, Silbergeld EK, Morris JG. Animal antibiotic use has an early but important impact on the emergence of antibiotic resistance in human commensal bacteria. Proc Natl Acad Sci U S A. 2002;99(9):6434-9.
Yılmaz EŞ, Aslantaş Ö. Antimicrobial resistance and underlying mechanisms in Staphylococcus aureus isolates. Asian Pac J Trop Med. 2017;10(11):1059-64.
Bag A, Chattopadhyay RR. Evaluation of synergistic antibacterial and antioxidant efficacy of essential oils of spices and herbs in combination. PLoS One. 2015;10(7):131321.
Liu GY. Molecular pathogenesis of Staphylococcus aureus infection. Pediatr Res. 2009;65(5 Pt 2):71R-7R.
Hu C, Xiong N, Zhang Y, Rayner S, Chen S. Functional characterization of lipase in the pathogenesis of Staphylococcus aureus. Biochem Biophys Res Commun. 2012;419(4):617-20.
Lowy FD. Staphylococcus aureus infections. N Engl J Med. 1998;339(8):520-32.
Mira AR, Zeferino AS, Inácio R, Delgadinho M, Brito M, Calado CR, et al. Epigenetic and drug response modulators patterns in Staphylococcus aureus with divergent resistance phenotypes. Antibiotics. 2023;12(3):519.
Ribeiro E, Ladeira C, Viegas S. EDCs mixtures: a stealthy hazard for human health? Toxics. 2017;5(1):5.
Bento A, Oliveira K, Vasques M, Ribeiro E. Atividade antagonista do leite fermentado por kefir contra Staphylococcus aureus resistentes à meticilina (MRSA) [Antagonistic activity of kefir fermented milk against methicillin-resistant Staphylococcus aureus (MRSA)]. Saúde & Tecnologia. 2020;(23):27-31. Portuguese
Ignasimuthu K, Prakash R, Murthy PS, Subban N. Enhanced bioaccessibility of green tea polyphenols and lipophilic activity of EGCG octa-acetate on gram-negative bacteria. LWT. 2019;105:103-9.
Singh BN, Shankar S, Srivastava RK. Green tea catechin, epigallocatechin-3-gallate (EGCG): mechanisms, perspectives, and clinical applications. Biochem Pharmacol. 2011;82(12):1807-21.
Martini N. Green tea. J Prim Health Care. 2016;8(4):381-2.
Reygaert WC. The antimicrobial possibilities of green tea. Front Microbiol. 2014;5:434.
Cai ZY, Li XM, Liang JP, Xiang LP, Wang KR, Shi YL, et al. Bioavailability of tea catechins and its improvement. Molecules. 2018;23(9):2346.
Chu C, Deng J, Man Y, Qu Y. Green tea extracts Epigallocatechin-3-gallate for different treatments. Biomed Res Int. 2017;2017:5615647.
Song JM, Seong BL. Tea catechins as a potential alternative anti-infectious agent. Expert Rev Anti Infect Ther. 2007;5(3):497-506.
Reygaert WC. Green tea catechins: their use in treating and preventing infectious diseases. Biomed Res Int. 2018;2018:9105261.
Das S, Tanwar J, Hameed S, Fatima Z. Antimicrobial potential of epigallocatechin-3-gallate (EGCG): a green tea polyphenol. J Biochem Pharmacol Res. 2017;2(3):167-74.
Haghjoo B, Lee LH, Habiba U, Tahir H, Olabi M, Chu TC. The synergistic effects of green tea polyphenols and antibiotics against potential pathogens. Adv Biosci Biotechnol. 2013;4(11):959-67.
Steinmann J, Buer J, Pietschmann T, Steinmann E. Anti-infective properties of epigallocatechin-3-gallate (EGCG), a component of green tea. Br J Pharmacol. 2013;168(5):1059-73.
Aboulmagd E, Al-Mohamme HI, Al-Badry S. Synergism and postantibiotic effect of green tea extract and imipenem against methicillin-resistant Staphylococcus aureus. Microbiol J. 2011;1(3):89-96.
Zeferino AS. Potencial antimicrobiano da epigalocatequina-3-galato do chá verde contra MRSA de isolados hospitalares e da comunidade [dissertation]. Lisboa: Escola Superior de Tecnologia da Saúde de Lisboa/Instituto Politécnico de Lisboa; 2020. Available from: https://repositorio.ipl.pt/handle/10400.21/12747
Mira AR. Epigenetic divergence of Staphylococcus aureus phenotypic resistant profiles and Epigallocatechin-3-Gallate modulator effect [dissertation]. Lisboa: Escola Superior de Tecnologia da Saúde de Lisboa/Instituto Politécnico de Lisboa; 2021. Available from: https://repositorio.ipl.pt/handle/10400.21/13992
Rasheed NA, Hussein NR. Staphylococcus aureus: an overview of discovery, characteristics, epidemiology, virulence factors and antimicrobial sensitivity. Eur J Mol Clin Med. 2021;8(3):1160-83.
Rosenbach FJ. Mikro-organismen bei den wund-infections-krankheiten des menschen [homepage]. Wiesbaden: J.F. Bergmann; 1884. Available from: https://www.biodiversitylibrary.org/bibliography/22955
Biedenbach DJ, Moet GJ, Jones RN. Occurrence and antimicrobial resistance pattern comparisons among bloodstream infection isolates from the SENTRY Antimicrobial Surveillance Program (1997-2002). Diagn Microbiol Infect Dis. 2004;50(1):59-69.
Peacock SJ, Paterson GK. Mechanisms of methicillin resistance in Staphylococcus aureus. Annu Rev Biochem. 2015;84(1):577-601.
Negrinho A, Ferreira B, Serrano D, Ribeiro E, Shone S. Prevalência da colonização nasal por Staphylococcus Aureus resistente à meticilina nos técnicos de análises clínicas e saúde pública num hospital do distrito de Lisboa: estudo de caso [The prevalence of nasal colonization by methicillin-resistant Staphylococcus aureus in the clinical analysis and public health technicians at a hospital in the district of Lisbon: a case study]. Saúde & Tecnologia. 2019;(22):34-41. Portuguese
Centers for Disease Control and Prevention. Combating antimicrobial resistance, a global threat [homepage]. CDC; 2021 [updated Dec 17; cited 2021 Jul 3]. Available from: https://www.cdc.gov/drugresistance/index.html
Kapoor G, Saigal S, Elongavan A. Action and resistance mechanisms of antibiotics: a guide for clinicians. J Anaesthesiol Clin Pharmacol. 2017;33(3):300-5.
Soares GM, Figueiredo LC, Faveri M, Cortelli SC, Duarte PM, Feres M. Mechanisms of action of systemic antibiotics used in periodontal treatment and mechanisms of bacterial resistance to these drugs. J Appl Oral Sci. 2012;20(3):295-309.
Harkins CP, Pichon B, Doumith M, Parkhill J, Westh H, Tomasz A, et al. Methicillin-resistant Staphylococcus aureus emerged long before the introduction of methicillin into clinical practice. Genome Biol. 2017;18(1):130.
Santos AL, Santos DO, de Freitas CC, Ferreira BL, Afonso IF, Rodrigues CR, et al. Staphylococcus aureus: visitando uma cepa de importância hospitalar [Staphylococcus aureus: visiting a strain of clinical importance]. J Bras Patol Med Lab. 2007;43(6):413-23. Portuguese
Peres D, Neves I, Vieira F, Devesa I. Estratégia para controlar o Staphylococcus aureus resistente à meticilina: a experiência de cinco anos de um hospital [Strategy to control methicillin-resistant Staphylococcus aureus: the 5 year experience of a hospital]. Acta Med Port. 2014;27(1):67-72. Portuguese
Tong SY, Davis JS, Eichenberger E, Holland TL, Fowler VG. Staphylococcus aureus infections: epidemiology, pathophysiology, clinical manifestations, and management. Clin Microbiol Rev. 2015;28(3):603-61.
Kos VN, Desjardins CA, Griggs A, Cerqueira G, van Tonder A, Holden MT, et al. Comparative genomics of vancomycin-resistant staphylococcus aureus strains and their positions within the clade most commonly associated with methicillin-resistant S. aureus hospital-acquired infection in the United States. mBio. 2012;3(3):e00112-12.
McGuinness WA, Malachowa N, DeLeo FR. Vancomycin resistance in Staphylococcus aureus. Yale J Biol Med. 2017;90(2):269-81.
Liu C, Bayer A, Cosgrove SE, Daum RS, Fridkin SK, Gorwitz RJ, et al. Clinical practice guidelines by the Infectious Diseases Society of America for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children: executive summary. Clin Infect Dis. 2011;52(3):285-92.
Gould IM, David MZ, Esposito S, Garau J, Lina G, Mazzei T, et al. New insights into meticillin-resistant Staphylococcus aureus (MRSA) pathogenesis, treatment and resistance. Int J Antimicrob Agents. 2012;39(2):96-104.
Häusler T. Viruses vs. superbugs: a solution to the antibiotics crisis? London: Palgrave Macmillan; 2006. ISBN 9780230552289
Morris A, Kellner JD, Low DE. The superbugs: evolution, dissemination, and fitness. Curr Opinion Microbiol. 1998;1(5):524-9.
Abbott A. Medics braced for fresh superbug. Nature. 2005;436(7052):758.
Brazier JS. Clostridium difficile: from obscurity to superbug. Br J Biomed Sci. 2008;65(1):39-44.
Ippolito G, Leone S, Lauria FN, Nicastri E, Wenzel RP. Methicillin-resistant Staphylococcus aureus: the superbug. Int J Infect Dis. 2010;14 Suppl 4:S7-11.
Guo Y, Wang J, Niu G, Shui W, Sun Y, Zhou H, et al. A structural view of the antibiotic degradation enzyme NDM-1 from a superbug. Protein Cell. 2011;2(5):384-94.
Turner NA, Sharma-Kuinkel BK, Maskarinec SA, Eichenberger EM, Shah PP, Carugati M, et al. Methicillin-resistant Staphylococcus aureus: an overview of basic and clinical research. Nature Rev Microbiol. 2019;17(4):203-18.
Zeferino AS, Mira AR, Delgadinho M, Brito M, Ponte E, Ribeiro E. Drug resistance and epigenetic modulatory potential of Epigallocatechin-3-gallate against Staphylococcus aureus. Curr Microbiol. 2022;79(5):149.
Gnanamani A, Hariharan P, Paul-Satyaseela M. Staphylococcus aureus: overview of bacteriology, clinical diseases, epidemiology, antibiotic resistance and therapeutic approach. In: Enany S, Alexander LE, editors. Frontiers in Staphylococcus aureus [homepage]. InTech; 2017. Available from: https://www.intechopen.com/chapters/54154
Sousa MA. Staphylococcus aureus resistente à meticilina (MRSA): um pesadelo para a saúde pública [Methicillin-resistant Staphylococcus aureus(MRSA): a public health nightmare]. Salutis Scientia. 2012;(4):18-30. Portuguese
Kateete DP, Bwanga F, Seni J, Mayanja R, Kigozi E, Mujuni B, et al. CA-MRSA and HA-MRSA coexist in community and hospital settings in Uganda. Antimicrob Resist Infect Control. 2019;8:94.
Gill SR, Fouts DE, Archer GL, Mongodin EF, DeBoy RT, Ravel J, et al. Insights on evolution of virulence and resistance from the complete genome analysis of an early methicillin-resistant Staphylococcus aureus strain and a biofilm-producing methicillin-resistant Staphylococcus epidermidis strain. J Bacteriol. 2005;187(7):2426.
Gordon RJ, Lowy FD. Pathogenesis of methicillin-resistant Staphylococcus aureus infection. Clin Infect Dis. 2008;46 Suppl 5:S350-9.
Smith TC. Livestock-associated Staphylococcus aureus: the United States experience. PLoS Pathog. 2015;11(2):e1004564.
Cruz AR, van Strijp JA, Bagnoli F, Manetti AG. Virulence gene expression of Staphylococcus aureus in human skin. Front Microbiol. 2021;12:692023.
Novick RP, Geisinger E. Quorum sensing in Staphylococci. Annu Rev Genet. 2008;42:541-64.
Wyatt MA, Wang W, Roux CM, Beasley FC, Heinrichs DE, Dunman PM, et al. Staphylococcus aureus nonribosomal peptide secondary metabolites regulate virulence. Science. 2010;329(5989):294-6.
Kaneko J, Kamio Y. Bacterial two-component and hetero-heptameric pore-forming cytolytic toxins: structures, pore-forming mechanism, and organization of the genes. Biosci Biotechnol Biochem. 2004;68(5):981-1003.
Kolar SL, Antonio Ibarra J, Rivera FE, Mootz JM, Davenport JE, Stevens SM, et al. Extracellular proteases are key mediators of Staphylococcus aureus virulence via the global modulation of virulence-determinant stability. Microbiologyopen. 2013;2(1):18-34.
Qin L, McCausland JW, Cheung GY, Otto M. PSM-Mec: a virulence determinant that connects transcriptional regulation, virulence, and antibiotic resistance in Staphylococci. Front Microbiol. 2016;7:1293.
Kong C, Neoh HM, Nathan S. Targeting Staphylococcus aureus toxins: a potential form of anti-virulence therapy. Toxins. 2016;8(3):72.
Chen Y, Yeh AJ, Cheung GY, Villaruz AE, Tan VY, Joo HS, et al. Basis of virulence in a panton-valentine leukocidin-negative community-associated MRSA strain. J Infect Dis. 2015;211(3):472-80.
Betts JW, Hornsey M, Wareham DW. In vitro activity of Epigallocatechin gallate (EGCG) and quercetin alone and in combination versus clinical isolates of methicillin-resistant Staphylococcus aureus. In: ASM 2014, Boston (USA), May 2014.
Das S, Tanwar J, Hameed S, Fatima Z. Antimicrobial potential of epigallocatechin-3-gallate (EGCG): a green tea polyphenol. J Biochem Pharmacol Res. 2014;2(3):167-74.
Gajdács M. The continuing threat of methicillin-resistant Staphylococcus aureus. Antibiotics. 2019;8(2):52.
Hu ZQ, Zhao WH, Asano N, Yoda Y, Hara Y, Shimamura T. Epigallocatechin gallate synergistically enhances the activity of carbapenems against methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother. 2002;46(2):558-60.
Roccaro AS, Blanco AR, Giuliano F, Rusciano D, Enea V. Epigallocatechin-gallate enhances the activity of tetracycline in staphylococci by inhibiting its efflux from bacterial cells. Antimicrob Agents Chemother. 2004;48(6):1968-73.
Wang X, Lin D, Huang Z, Zhang J, Xie W, Liu P, et al. Clonality, virulence genes, and antibiotic resistance of Staphylococcus aureus isolated from blood in Shandong, China. BMC Microbiol. 2021;21(1):281.
El-Baz R, Rizk DE, Barwa R, Hassan R. Virulence characteristics and molecular relatedness of methicillin resistant Staphylococcus aureus harboring different staphylococcal cassette chromosome mec. Microb Pathog. 2017;113:385-95.
Li H, Andersen PS, Stegger M, Sieber RN, Ingmer H, Staubrand N, et al. Antimicrobial resistance and virulence gene profiles of methicillin-resistant and -susceptible Staphylococcus aureus from food products in Denmark. Front Microbiol. 2019;10:2681.
Ikigai H, Nakae T, Hara Y, Shimamura T. Bactericidal catechins damage the lipid bilayer. Biochim Biophys Acta. 1993;1147(1):132-6.
Kitichalermkiat A, Kurahachi M, Nonaka A, Nakayama M, Shimatani K, Shigemune N, et al. Effects of Epigallocatechin gallate on viability and cellular proteins of Staphylococcus aureus. Food Sci Technol Res. 2019;25(2):277-85.
Lee S, Razqan GS al, Kwon DH. Antibacterial activity of epigallocatechin-3-gallate (EGCG) and its synergism with β-lactam antibiotics sensitizing carbapenem-associated multidrug resistant clinical isolates of Acinetobacter baumannii. Phytomedicine. 2017;24:49-55.
Kitichalermkiat A, Katsuki M, Sato J, Sonoda T, Masuda Y, Honjoh K ichi, et al. Effect of epigallocatechin gallate on gene expression of Staphylococcus aureus. J Glob Antimicrob Resist. 2020;22:854-9.
Du GJ, Zhang Z, Wen XD, Yu C, Calway T, Yuan CS, et al. Epigallocatechin gallate (EGCG) is the most effective cancer chemopreventive polyphenol in green tea. Nutrients. 2012;4:1679-91.
Kanagaratnam R, Sheikh R, Alharbi F, Kwon DH. An efflux pump (MexAB-OprM) of Pseudomonas aeruginosa is associated with antibacterial activity of Epigallocatechin-3-gallate (EGCG). Phytomedicine. 2017;36:194-200.
Venkatasubramaniam A, Kanipakala T, Ganjbaksh N, Mehr R, Mukherjee I, Krishnan S, et al. A critical role for HlgA in Staphylococcus aureus pathogenesis revealed by A Switch in the SaeRS two-component regulatory system. Toxins. 2018;10(9):377.
Pankey GA, Sabath LD. Clinical relevance of bacteriostatic versus bactericidal mechanisms of action in the treatment of gram-positive bacterial infections. Clin Infect Dis. 2004;38(6):864-70.
Fuchs S, Mehlan H, Bernhardt J, Hennig A, Michalik S, Surmann K, et al. AureoWiki ̵ The repository of the Staphylococcus aureus research and annotation community. Int J Med Microbiol. 2018;308(6):558-68.
Motamedi H, Asghari B, Tahmasebi H, Arabestani M. Identification of hemolysine genes and their association with antimicrobial resistance pattern among clinical isolates of Staphylococcus aureus in West of Iran. Adv Biomed Res. 2018;7:153.
Nasaj M, Saeidi Z, Asghari B, Roshanaei G, Arabestani MR. Identification of hemolysin encoding genes and their association with antimicrobial resistance pattern among clinical isolates of coagulase-negative Staphylococci. BMC Res Notes. 2020;13(1):68.
Callegan MC, Engel LS, Hill JM, O’Callaghan RJ. Corneal virulence of Staphylococcus aureus: roles of alpha-toxin and protein A in pathogenesis. Infect Immun. 1994;62(6):2478-82.
Wadström T, Eliasson I, Holder I, Ljungh A, editors. Pathogenesis of wound and biomaterial-associated infections. London: Springer; 1990. ISBN 9781447134541
Bramley AJ, Patel AH, O’Reilly M, Foster R, Foster TJ. Roles of alpha-toxin and beta-toxin in virulence of Staphylococcus aureus for the mouse mammary gland. Infect Immun. 1989;57(8):2489-94.
Almeida RP. Modulatory effect of Epigallocatechin-3 gallate in staphylococcus aureus toxin production genes transcription [dissertation]. Lisboa: Escola Superior de Saúde da Tecnologia de Lisboa/Instituto Politécnico de Lisboa; 2022.
Araújo R, Ramalhete L, Paz H, Ribeiro E, Calado CR. A simple, label-free, and high-throughput method to evaluate the Epigallocatechin-3-gallate impact in plasma molecular profile. High Throughput. 2020;9(2):9.
Negri A, Naponelli V, Rizzi F, Bettuzzi S. Molecular targets of Epigallocatechin-gallate (EGCG): a special focus on signal transduction and cancer. Nutrients. 2018;10(12):1936.
Vahid F, Zand H, Nosrat-Mirshekarlou E, Najafi R, Hekmatdoost A. The role dietary of bioactive compounds on the regulation of histone acetylases and deacetylases: a review. Gene. 2015;562(1):8-15.
Ghosh D, Veeraraghavan B, Elangovan R, Vivekanandan P. Antibiotic resistance and epigenetics: more to it than meets the eye. Antimicrob Agents Chemother. 2020;64(2):e02225-19.
Oliveira PH, Fang G. Conserved DNA methyltransferases: a window into fundamental mechanisms of epigenetic regulation in bacteria. Trends Microbiol. 2021;29(1):28-40.
Downloads
Publicado
Edição
Secção
Licença
Direitos de Autor (c) 2023 Saúde & Tecnologia
Este trabalho encontra-se publicado com a Licença Internacional Creative Commons Atribuição-NãoComercial-SemDerivações 4.0.
A revista Saúde & Tecnologia oferece acesso livre imediato ao seu conteúdo, seguindo o princípio de que disponibilizar gratuitamente o conhecimento científico ao público proporciona maior democratização mundial do conhecimento.
A revista Saúde & Tecnologia não cobra, aos autores, taxas referentes à submissão nem ao processamento de artigos (APC).
Todos os conteúdos estão licenciados de acordo com uma licença Creative Commons CC-BY-NC-ND. Os autores têm direito a: reproduzir o seu trabalho em suporte físico ou digital para uso pessoal, profissional ou para ensino, mas não para uso comercial (incluindo venda do direito a aceder ao artigo); depositar no seu sítio da internet, da sua instituição ou num repositório uma cópia exata em formato eletrónico do artigo publicado pela Saúde & Tecnologia, desde que seja feita referência à sua publicação na Saúde & Tecnologia e o seu conteúdo (incluindo símbolos que identifiquem a revista) não seja alterado; publicar em livro de que sejam autores ou editores o conteúdo total ou parcial do manuscrito, desde que seja feita referência à sua publicação na Saúde & Tecnologia.
