Efeito antifúngico de um metabólito de Pseudomonas aeruginosa cepa LV sobre Candida albicans resistente a azóis

Autores

DOI:

https://doi.org/10.46311/2318-0579.61.eUJ4662

Palavras-chave:

Antibiofilme, atividade antimicrobiana, fluopsina C, fungicida.

Resumo

Candida albicans permanece como agente mais comum de candidíase em todo o mundo. Essa levedura é geralmente sensível à maioria dos antifúngicos, entretanto o surgimento de C. albicans resistentes aos azóis tem sido relatado. Além disso, esse microrganismo pode formar biofilmes em diversas superfícies, dificultando o tratamento das infecções. Neste estudo, avaliou-se o efeito de metabólitos secundários de Pseudomonas aeruginosa cepa LV em células planctônicas e sésseis de C. albicans, com diferentes genótipos e perfil de sensibilidade ao fluconazol e ao voriconazol. A concentração inibitória mínima (CIM) e concentração fungicida mínima (CFM) da fração semipurificada F4a variaram de 1,56 a 6,25 µg/mL e 6,25 a 25 µg/mL, respectivamente. Fluopsina C parece ser o componente antifúngico de F4a. A fração semipurificada e fluopsina C apresentaram atividade fungicida dose e tempo dependentes. F4a causou graves danos à morfologia e à ultraestrutura das células fúngicas planctônicas, e reduziu significativamente a viabilidade de biofilmes de 24 horas, com CIM para células sésseis de 12,5 a 25,0 µg/mL. Detectou-se, entretanto, citotoxicidade em células de mamíferos para F4a e fluopsina C em concentrações que apresentaram atividade antifúngica. Estes resultados indicam que a fluopsina C pode ser um protótipo para o desenvolvimento de novos antifúngicos para C. albicans.

Downloads

Não há dados estatísticos.

Referências

Afonso, L., Andreata, M. F. D. L., Chryssafidis, A. L., Alarcon, S. F., Neves, A. P. das., Silva, J. V. F. R. da., & Andrade, G. (2022). Fluopsin C: a review of the antimicrobial activity against Phytopathogens. Agronomy, 12(12), p. 2997. doi: 10.3390/agronomy12122997 DOI: https://doi.org/10.3390/agronomy12122997

Alves de Lima, L. V., Silva, M. F. da., Concato, V. M., Rondina, D. B. L., Zanetti, T. A., Felicidade, I., & Mantovani, M. S. (2022). DNA damage and reticular stress in cytotoxicity and oncotic cell death of MCF-7 cells treated with fluopsin C. Journal of Toxicology and Environmental Health A, 85(21), pp. 896-911. doi: 10.1080/15287394.2022.2108950 DOI: https://doi.org/10.1080/15287394.2022.2108950

Atiencia-Carrera, M. B., Cabezas-Mera, F. S., Tejera, E., & Machado, A. (2022). Prevalence of biofilms in Candida spp. bloodstream infections: a meta-analysis. PLoS One, 17(2), p. e0263522. doi: 10.1371/journal.pone.0263522 DOI: https://doi.org/10.1371/journal.pone.0263522

Bansal, H., Singla, R. K., Behzad, S., Chopra, H., Grewal, A. S., & Shen, B. (2021). Unleashing the potential of microbial natural products in drug discovery: focusing on streptomyces as antimicrobials goldmine. Current Topics in Medicinal Chemistry, 21(26), pp. 2374-2396. doi: 10.2174/1568026621666210916170110 DOI: https://doi.org/10.2174/1568026621666210916170110

Barry, L. A., Craig, W. A., Nadler, H., Reller, L. B., Sanders, C. C., & Swenson, J. M. (1999). Methods for determining bactericidal activity of antimicrobial agents; approved guideline. National Committee for Clinical Laboratory Standards.

Bartolomeu-Gonçalves, G., Moreira, C. L., Andriani, G. M., Simionato, A. S., Nakamura, C. V., Andrade, G., & Yamada-Ogatta, S. F. (2022). Secondary metabolite from Pseudomonas aeruginosa LV strain exhibits antibacterial activity against Staphylococcus aureus: Metabólito secundário de Pseudomonas aeruginosa cepa LV exibe atividade antibacteriana em Staphylococcus aureus. Brazilian Journal of Development, 8(10), pp. 67414-67435. doi: 10.34117/bjdv8n10-170 DOI: https://doi.org/10.34117/bjdv8n10-170

Bedoya, J. C., Dealis, M. L., Silva, C. S., Niekawa, E. T. G., Navarro, M. O. P., Simionato, A. S., & Andrade, G. (2019). Enhanced production of target bioactive metabolites produced by Pseudomonas aeruginosa LV strain. Biocatalysis and Agricultural Biotechnology, 17, pp. 545-556. doi: 10.1016/j.bcab.2018.12.024 DOI: https://doi.org/10.1016/j.bcab.2018.12.024

Bizerra, F. C., Nakamura, C. V., Poersch, C. de., Estivalet Svidzinski, T. I., Borsato Quesada, R. M., Goldenberg, S., & Yamada-Ogatta, S. F. (2008). Characteristics of biofilm formation by Candida tropicalis and antifungal resistance. FEMS Yeast Research, 8(3), pp. 442-450. doi: 10.1111/j.1567-1364.2007.00347.x DOI: https://doi.org/10.1111/j.1567-1364.2007.00347.x

Bretagne, S., Sitbon, K., Desnos-Ollivier, M., Garcia-Hermoso, D., Letscher-Bru, V., Cassaing, S., & French Mycoses Study Group. (2022). Active surveillance program to increase awareness on invasive fungal diseases: the French RESSIF network (2012 to 2018). Mbio, 13(3), pp. e00920-22. doi: 10.1128/mbio.00920-22 DOI: https://doi.org/10.1128/mbio.00920-22

Clinical and Laboratory Standards Institute. (2017). Reference method for broth dilution antifungal susceptibility testing of yeasts. 4th ed. CLSI Standard M60. Wayne, PA, USA: CLSI.

Clinical and Laboratory Standards Institute. (2022). Performance standards for antifungal susceptibility testing of yeasts. 3rd ed. CLSI supplement M27M44S. Wayne, PA, USA: CLSI.

Del Rio, L. A., Gorgé, J. L., Olivares, J., & Mayor, F. (1972). Antibiotics from Pseudomonas reptilivora II. Isolation, purification, and properties. Antimicrobial Agents and Chemotherapy, 2(3), pp. 189-194. doi: 10.1128/AAC.2.3.189 DOI: https://doi.org/10.1128/AAC.2.3.189

Egawa, Y., Umino, K., Awataguchi, S., Kawano, Y., & Okuda, T. (1970). Antibiotic YC 73 of Pseudomonas origin. 1. Production, isolation and properties. The Journal of Antibiotics, 23(6), pp. 267-70. doi: 10.7164/antibiotics.23.267 DOI: https://doi.org/10.7164/antibiotics.23.267

Egawa, Y., Umino, K., Ito, Y., & Okuda, T. (1971). Antibiotic YC 73 of Pseudomonas origin. II. Structure and synthesis of thioformin and its cupric complex (YC 73). The Journal of Antibiotics, 24(2), pp. 124-130. doi: 10.7164/antibiotics.24.124 DOI: https://doi.org/10.7164/antibiotics.24.124

Eldesouky, H. E, Mayhoub, A., Hazbun, T. R., & Seleem, M. N. (2018). Reversal of azole resistance in Candida albicans by sulfa antibacterial drugs. Antimicrobial Agents and Chemotherapy, 62(3), pp. e00701-17. doi: 10.1128/AAC.00701-17 DOI: https://doi.org/10.1128/AAC.00701-17

Endo, E. H., Cortez, D. A. G., Ueda-Nakamura, T., Nakamura, C. V., & Dias Filho, B. P. (2010). Potent antifungal activity of extracts and pure compound isolated from pomegranate peels and synergism with fluconazole against Candida albicans. Research in Microbiology, 161(7), pp. 534-540. doi: 10.1016/j.resmic.2010.05.002 DOI: https://doi.org/10.1016/j.resmic.2010.05.002

Fan, F., Liu, Y., Liu, Y., Lv, R., Sun, W., Ding, W., & Qu, W. (2022). Candida albicans biofilms: antifungal resistance, immune evasion, and emerging therapeutic strategies. International Journal of Antimicrobial Agents, 60(5-6), p. 106673. doi: 10.1016/j.ijantimicag.2022.106673 DOI: https://doi.org/10.1016/j.ijantimicag.2022.106673

Gross, H., & Loper, J. E. (2009). Genomics of secondary metabolite production by Pseudomonas spp. Natural Product Reports, 26(11), pp. 1408-1446. doi: 10.1039/b817075b DOI: https://doi.org/10.1039/b817075b

Heras, J., Domínguez, C., Mata, E., Pascual, V., Lozano, C., Torres, C., & Zarazaga, M. (2015). GelJ–a tool for analyzing DNA fingerprint gel images. BMC Bioinformatics, 16(1), pp. 1-8. doi: 10.1186/s12859-015-0703-0 DOI: https://doi.org/10.1186/s12859-015-0703-0

Itoh, S., Inuzuka, K., & Suzuki, T. (1970). New antibiotics produced by bacteria grown on n-paraffin (mixture of C12, C13 and C14 fractions). The Journal of Antibiotics, 23(11), pp. 542-545. doi: 10.7164/antibiotics.23.542 DOI: https://doi.org/10.7164/antibiotics.23.542

Kerbauy, G., Vivan, A. C., Simões, G. C., Simionato, A. S., Pelisson, M., Vespero, E. C., & Andrade, G. (2016). Effect of a metalloantibiotic produced by Pseudomonas aeruginosa on Klebsiella pneumoniae Carbapenemase (KPC)-producing K. pneumoniae. Current Pharmaceutical Biotechnology, 17(4), pp. 389-97. doi: 10.2174/138920101704160215171649 DOI: https://doi.org/10.2174/138920101704160215171649

Kerr, J. R., Taylor, G. W., Rutman, A., Høiby, N., Cole, P. J., & Wilson, R. (1999). Pseudomonas aeruginosa pyocyanin and 1-hydroxyphenazine inhibit fungal growth. Journal of Clinical Pathology, 52(5), p. 385. doi: 10.1136/jcp.52.5.385 DOI: https://doi.org/10.1136/jcp.52.5.385

Klepser, M. E., Ernst, E. J., Lewis, R. E., Ernst, M. E., & Pfaller, M. A. (1998). Influence of test conditions on antifungal time-kill curve results: proposal for standardized methods. Antimicrobial Agents and Chemotherapy, 42(5), pp. 1207-1212. doi: 10.1128/AAC.42.5.1207 DOI: https://doi.org/10.1128/AAC.42.5.1207

Lopes, J. P., & Lionakis, M. S. (2022). Pathogenesis and virulence of Candida albicans. Virulence, 13(1), pp. 89-121. doi: 10.1080/21505594.2021.2019950 DOI: https://doi.org/10.1080/21505594.2021.2019950

Ma, L. S., Jiang, C. Y., Cui, M., Lu, R., Liu, S. S., Zheng, B. B., & Li, X. (2013). Fluopsin C induces oncosis of human breast adenocarcinoma cells. Acta Pharmacologica Sinica, 34(8), pp. 1093-100. doi: 10.1038/aps.2013.44 DOI: https://doi.org/10.1038/aps.2013.44

Morey, A. T., Souza, F. C. de., Santos, J. P., Pereira, C. A., Cardoso, J. D., Almeida, R. S. de., & Yamada-Ogatta, S. F. (2016). Antifungal activity of condensed tannins from Stryphnodendron adstringens: effect on Candida tropicalis growth and adhesion properties. Current Pharmaceutical Biotechnology, 17(4), pp. 365-75. doi: 10.2174/1389201017666151223123712 DOI: https://doi.org/10.2174/1389201017666151223123712

Moyes, D. L., Runglall, M., Murciano, C., Shen, C., Nayar, D., Thavaraj, S., & Naglik, J. R. (2010). A biphasic innate immune MAPK response discriminates between the yeast and hyphal forms of Candida albicans in epithelial cells. Cell Host & Microbe, 8(3), pp. 225-235. doi: 10.1016/j.chom.2010.08.002 DOI: https://doi.org/10.1016/j.chom.2010.08.002

Navarro, M. O. P., Simionato, A. S., Pérez, J. C. B., Barazetti, A. R., Emiliano, J., Niekawa, E. T. G., & Andrade, G. (2019). Fluopsin C for treating multidrug-resistant infections: in vitro activity against clinically important strains and in vivo efficacy against carbapenemase-producing Klebsiella pneumoniae. Frontiers in Microbiology, 10, p. 2431. doi: 10.3389/fmicb.2019.02431 DOI: https://doi.org/10.3389/fmicb.2019.02431

Noble, S. M., Gianetti, B. A., & Witchley, J. N. (2017). Candida albicans cell-type switching and functional plasticity in the mammalian host. Nature Reviews Microbiology, 15(2), pp. 96-108. doi: 10.1038/nrmicro.2016.157 DOI: https://doi.org/10.1038/nrmicro.2016.157

Noumi, E., Snoussi, M., Saghrouni, F., Ben Said, M., Del Castillo, L., Valentin, E., & Bakhrouf, A. (2009). Molecular typing of clinical Candida strains using random amplified polymorphic DNA and contour‐clamped homogenous electric fields electrophoresis. Journal of Applied Microbiology, 107(6), pp. 1991-2000. doi: 10.1111/j.1365-2672.2009.04384.x DOI: https://doi.org/10.1111/j.1365-2672.2009.04384.x

Otsuka, H., Niwayama, S., Tanaka, H., Take, T., & Uchiyama, T. (1971). An antitumor antibiotic, no. 4601 from Streptomyces, identical with YC 73 of Pseudomonas origin. The Journal of Antibiotics, 25(6), pp. 369-70. doi: 10.7164/antibiotics.25.369 DOI: https://doi.org/10.7164/antibiotics.25.369

Patel, M. (2022). Oral cavity and Candida albicans: colonisation to the development of infection. Pathogens, 11(3), p. 335. doi: 10.3390/pathogens11030335 DOI: https://doi.org/10.3390/pathogens11030335

Patteson, J. B., Putz, A. T., Tao, L., Simke, W. C., Bryant III, L. H., Britt, R. D., & Li, B. (2021). Biosynthesis of fluopsin C, a copper-containing antibiotic from Pseudomonas aeruginosa. Science, 374(6570), pp. 1005-1009. doi: 10.1126/science.abj6749 DOI: https://doi.org/10.1126/science.abj6749

Salvatori, O., Kumar, R., Metcalfe, S., Vickerman, M., Kay, J. G., & Edgerton, M. (2020). Bacteria modify Candida albicans hypha formation, microcolony properties, and survival within macrophages. mSphere, 5(4), p. e00689-20. doi: 10.1128/mSphere.00689-20 DOI: https://doi.org/10.1128/msphere.00689-20

Saville, S. P., Lazzell, A. L., Monteagudo, C., & Lopez-Ribot, J. L. (2003). Engineered control of cell morphology in vivo reveals distinct roles for yeast and filamentous forms of Candida albicans during infection. Eukaryotic Cell, 2(5), pp. 1053-1060. doi: 10.1128/EC.2.5.1053-1060.2003 DOI: https://doi.org/10.1128/EC.2.5.1053-1060.2003

Shafiei, M., Peyton, L., Hashemzadeh, M., & Foroumadi, A. (2020). History of the development of antifungal azoles: a review on structures, SAR, and mechanism of action. Bioorganic Chemistry, 104, p. 104240. DOI: https://doi.org/10.1016/j.bioorg.2020.104240

Sharifi, M., Badiee, P., Abastabar, M., Morovati, H., Haghani, I., Noorbakhsh, M., & Mohammadi, R. (2023). A 3-year study of Candida infections among patients with malignancy: etiologic agents and antifungal susceptibility profile. Frontiers in Cellular and Infection Microbiology, 13, p. 555. doi: 10.3389/fcimb.2023.1152552 DOI: https://doi.org/10.3389/fcimb.2023.1152552

Spoladori, L. F. D. A., Andriani, G. M., Castro, I. M. D., Suzukawa, H. T., Gimenes, A. C. R., Bartolomeu-Gonçalves, G., & Yamada-Ogatta, S. F. (2023). Synergistic antifungal interaction between Pseudomonas aeruginosa LV strain metabolites and biogenic silver nanoparticles against Candida auris. Antibiotics, 12(5), p. 861. doi: 10.3390/antibiotics12050861 DOI: https://doi.org/10.3390/antibiotics12050861

Ward, T. L., Dominguez-Bello, M. G., Heisel, T., Al-Ghalith, G., Knights, D., & Gale, C. A. (2018). Development of the human mycobiome over the first month of life and across body sites. mSystems, 3(3), pp. 10-1128. doi: 10.1128/mSystems.00140-17 DOI: https://doi.org/10.1128/mSystems.00140-17

World Health Organization. (2022). Fungal priority pathogens list to guide research, development and Public Health action. World Health Organization: Geneva, Switzerland. Retrieved from https://www.who.int/publications/i/item/9789240060241

Publicado

2024-08-12

Como Citar

Moreira, C. L., Bartolomeu-Gonçalves, G., Silva-Rodrigues, G., Simionato, A. S. ., Nakamura, C. V. ., Rodrigues, M. V. P. ., Andrade, G., Reis Tavares, E., Yamauchi, L. M., & Yamada-Ogatta, S. F. (2024). Efeito antifúngico de um metabólito de Pseudomonas aeruginosa cepa LV sobre Candida albicans resistente a azóis. Revista Uningá, 61, eUJ4662. https://doi.org/10.46311/2318-0579.61.eUJ4662

Edição

Seção

Biológicas I, II e III

Artigos mais lidos pelo mesmo(s) autor(es)