Universidade Federal de Santa Maria, UFSM, Departamento de Análises Clínicas e Toxicológicas, Avenida Roraima, nº 1000, Cidade Universitária, Bairro Camobi, CEP: 97105-900, Santa Maria, RS, Brasil.
Licenciada em Ciências Biológicas pela Universidade Regional Integrada do Alto Uruguai e das Missões (URI), Especialista em Análises Clínicas pela Universidade Franciscana (UFN), Mestre em Ciências da Saúde e da Vida (UFN). Doutoranda no Programa de Pós-Graduação em Ciências Farmacêuticas - Análises Clínicas e Toxicológicas, pela Universidade Federal de Santa Maria (UFSM).
Técnica em Química com Ênfase em Produção Industrial. Graduada em Engenharia de Alimentos e licenciada em Química pela Universidade Federal do Rio Grande (FURG). Mestre e Doutora em Engenharia e Ciência de Alimentos pela FURG. Técnica de laboratório no Centro de Ciências da Químicas, Farmacêuticas e de Alimentos da Universidade Federal de Pelotas.
Graduado em Farmácia pela Universidade Federal de Santa Maria (UFSM), Mestre em Ciências Farmacêuticas (UFSM) e Doutorando no Programa de Pós-Graduação em Ciências Farmacêuticas - Análises Clínicas e Toxicológicas (UFSM). Técnico de laboratório na área de Química do Departamento de Defesa Fitossanitária da UFSM
Licenciada em Química pela Universidade Federal de Santa Maria (UFSM), Mestre em Química Analítica (UFSM), Doutora em Química (UFSM). Técnica de laboratório na área de Química no Departamento de Farmácia Industrial da UFSM.
Graduada em Farmácia Bioquímica pela Universidade Estadual Paulista Júlio de Mesquita Filho (UNESP), Mestre em Ciências Biológicas - Microbiologia Aplicada (UNESP) e Doutora em Farmácia - Análises Clínicas pela Universidade de São Paulo (USP). Professora Titular da Universidade Federal de Santa Maria (UFSM).
This study investigated the effect of Bauhinia forficata subsp. pruinosa leaf extract on four mycobacterial species and their biofilms, as well as its phenolic content. Phytochemical assays (total phenolic and flavonoid content, chromatographic analysis) and microbiological evaluations (minimum inhibitory concentration – MIC; minimum bactericidal concentration – MBC, time-kill curve, checkerboard assay, and antibiofilm assessment) were performed. Rutin was identified as the major compound. The extract exhibited an MIC of 0.31 mg/mL-1 for all tested strains; however, Mycobacteroides massiliense showed lower susceptibility, considering its MBC value and behavior in the time-kill curve. Additionally, the extract inhibited and eradicated biofilms of M. massiliense and Mycolicibacterium fortuitum and eradicated those of Mycobacteroides abscessus and Mycolicibacterium smegmatis when applied at the MIC value. Furthermore, the extract displayed an additive effect against M. abscessus and M. smegmatis in combination with clarithromycin and against M. massiliense when combined with imipenem. This study is the first to report the in vitro antimycobacterial and antibiofilm activity of B. forficata subsp. pruinosa leaf extract. The positive effects observed are partially attributed to the flavonol rutin. Our findings suggest its potential use as an adjuvant in the treatment of mycobacterial infections, addressing antibiotic resistance issues.
References
Gupta RS, Lo B, Son J. Phylogenomics and Comparative Genomic Studies Robustly Support Division of the Genus Mycobacterium into an Emended Genus Mycobacterium and Four Novel Genera. Front Microbiol. 2018; 13(9): 67. Available at: [https://doi.org/10.3389/fmicb.2018.00067].
Koo H, Falsetta ML, Klein MI. The exopolysaccharide matrix: a virulence determinant of cariogenic biofilm. J Dent Res. 2013; 92(12): 1065-73. Available at: [https://doi.org/10.1177/0022034513504218].
Barai L, Saha MR, Rahman T, Sukanya M, Ferdous J, Khanduker A, et al. Pattern of rapidly growing mycobacteria (RGM) species isolated from clinical samples: A 10-year retrospective study in a tertiary care hospital of Bangladesh. Indian J Med Microbiol. 2024; 5(53): 100756. Available at: [https://doi.org/10.1016/j.ijmmb.2024.100756].
Jung EP, de Freitas BP, Kunigami CN, Moreira DL, de Figueiredo NG, Ribeiro LO, et al. Bauhinia forficata Link Infusions: Chemical and Bioactivity of Volatile and Non-Volatile Fractions. Molecules. 2022; 27(17): 5415. Available at: [https://doi.org/10.3390/molecules27175415].
Lorenzi H, Matos FJA. Medicinal plants in Brazil: native and exotic. 3th ed. Nova Odessa: Plantarum Botanical Garden; 2021.
Miceli N, Buongiorno LP, Celi MG, Cacciola F, Dugo P, Donato P, et al. Role of the flavonoid-rich fraction in the antioxidant and cytotoxic activities of Bauhinia forficata Link. (Fabaceae) leaves extract. Nat Prod Res. 2016; 30(11): 1229-39. Available at: [https://doi.org/10.1080/14786419.2015.1050671].
De Sousa JN, de Oliveira ABM, Ferreira AK, Silva E, de Sousa LMS, França Rocha MC, et al. Modulation of the resistance to norfloxacin in Staphylococcus aureus by Bauhinia forficata link. Nat Prod Res. 2021; 35(4): 681-5. Available at: [https://doi.org/10.1080/14786419.2019.1590714].
Ferreira-Filho JCC, Marre ATO, De Sá Almeida JS, Lobo LA, Farah A, Romanos MTV, et al. Therapeutic Potential of Bauhinia forficata Link in Dental Biofilm Treatment. J Med Food. 2020; 23(9): 998–1005. Available at: [https://doi.org/10.1089/JMF.2019.0277].
Silva FLL, Scotti AS, Garcia ALH, Lemes MLB, Grivicich I, Reis GM, et al. Toxicological potential of Aloysia gratissima: Insights from chemical analysis and in vitro studies. J Ethnopharmacol. 2023;314: 116614. Available at: [https://doi.org/10.1016/J.JEP.2023.116614].
Menezes APS, Silva J, Fisher C, Silva FR, Reyes JM, Picada JN, et al. Chemical and toxicological effects of medicinal Baccharis trimera extract from coal burning area. Chemosphere. 2016; 146: 396-404. Available at: [https://doi.org/10.1016/J.CHEMOSPHERE.2015.12.028].
Rossi GG, Guterres KB, Moreira KS, Burgo TAL, de Campos MMA, Iglesias BA. Photo-damage promoted by tetra-cationic palladium (II) porphyrins in rapidly growing mycobacteria. Photodiagnosis Photodyn Ther. 2021; 36: 102514. Available at: [https://doi.org/10.1016/J.PDPDT.2021.102514].
Nikolic I, Vukovic D, Gavric D, Cvetanovic J, Aleksic Sabo V, Gostimirovic S, et al. An Optimized Checkerboard Method for Phage-Antibiotic Synergy Detection. Viruses. 2022; 14(7): 1542. Available at: [https://doi.org/10.3390/V14071542/S1].
Bonez PC, Agertt VA, Rossi GG, Siqueira FS, Siqueira JD, Marques LL, et al. Sulfonamides complexed with metals as mycobacterial biofilms inhibitors. J Clin Tuberc Other Mycobact Dis. 2021; 23: 100217. Available at: [https://doi.org/10.1016/J.JCTUBE.2021.100217].
Sayago C, Camargo V, Barbosa F, Gularte C, Pereira G, Miotto S, et al. Chemical composition and in vitro antioxidant activity of hydro-ethanolic extracts from Bauhinia forficata subsp. pruinosa and B. variegata. Acta Biol Hung. 2013; 64(1): 21-33. Available at: [https://doi.org/10.1556/ABIOL.64.2013.1.3].
Franco RR, Alves VHM, Zabisky LFR, Justino AB, Martins MM, Saraiva AL, et al. Antidiabetic potential of Bauhinia forficata Link leaves: a non-cytotoxic source of lipase and glycoside hydrolases inhibitors and molecules with antioxidant and antiglycation properties. Biomed Pharmacother. 2020; 123: 109798. Available at: [https://doi.org/10.1016/J.BIOPHA.2019.109798].
Ecker A, Vieira FA, Prestes AS, Dos Santos MM, Ramos A, Ferreira RD, et al. Effect of Syzygium cumini and Bauhinia forficata aqueous-leaf extracts on oxidative and mitochondrial parameters in vitro. EXCLI J. 2015; 14: 1219-31. Available at: [https://doi.org/10.17179/EXCLI2015-576].
Sotiropoulou ΝSD, Flampouri E, Skotti E, Pappas C, Kintzios S, Tarantilis PA. Bioactivity and toxicity evaluation of infusions from selected Greek herbs. Food Biosci. 2020; 35: 100598. Available at: [https://doi.org/10.1016/J.FBIO.2020.100598].
Farag MA, Sakna ST, El-Fiky NM, Shabana MM, Wessjohann LA. Phytochemical, antioxidant and antidiabetic evaluation of eight Bauhinia L. species from Egypt using UHPLC–PDA–qTOF-MS and chemometrics. Phytochemistry. 2015; 119: 41-50. Available at: [https://doi.org/10.1016/J.PHYTOCHEM.2015.09.004].
Roy A, Khan A, Ahmad I, Alghamdi S, Rajab BS, Babalghith AO, et al. Flavonoids a Bioactive Compound from Medicinal Plants and Its Therapeutic Applications. Biomed Res Int. 2022; 2022: 5445291. Available at: [https://doi.org/10.1155/2022/5445291].
Wang Z, Ding Z, Li Z, Ding Y, Jiang F, Liu J. Antioxidant and antibacterial study of 10 flavonoids revealed rutin as a potential antibiofilm agent in Klebsiella pneumoniae strains isolated from hospitalized patients. Microb Pathog. 2021; 159: 105121. Available at: [https://doi.org/10.1016/J.MICPATH.2021.105121].
Cheng A, Sheng WH, Huang YC, Sun HY, Tsai YT, Chen ML, et al. Prolonged postprocedural outbreak of Mycobacterium massiliense infections associated with ultrasound transmission gel. Clin Microbiol Infect. 2016; 22(4): 382.e1-382.e11. Available at: [https://doi.org/10.1016/J.CMI.2015.11.021].
Koh WJ, Jeong BH, Jeon K, Kim SY, Park KU, Park HY, et al. Oral Macrolide Therapy Following Short-term Combination Antibiotic Treatment of Mycobacterium massiliense lung disease. Chest. 2016; 150(6): 1211-21. Available at: [https://doi.org/10.1016/J.CHEST.2016.05.003].
Donohue MJ. Epidemiological risk factors and the geographical distribution of eight Mycobacterium species. BMC Infect Dis. 2021; 21(1): 258. available at: [https://doi.org/10.1186/S12879-021-05925-Y].
Cowman S, Van Ingen J, Griffith DE, Loebinger MR. Non-tuberculous mycobacterial pulmonary disease. Eur Respir J. 2019; 54(1): 1900250. Available at: [https://doi.org/10.1183/13993003.00250-2019].
Teng R, Dick T. Isoniazid resistance of exponentially growing Mycobacterium smegmatis biofilm culture. FEMS Microbiol Lett. 2003; 227(2): 171-4. Available at: [https://doi.org/10.1016/S0378-1097(03)00584-6].
Shivaprasad DP, Taneja NK, Lakra A, Sachdev D. In vitro and in situ abrogation of biofilm formation in E. coli by vitamin C through ROS generation, disruption of quorum sensing and exopolysaccharide production. Food Chem. 2021; 341(1): 128171. Available at: [https://doi.org/10.1016/J.FOODCHEM.2020.128171].
Peng LY, Yuan M, Cui ZQ, Wu ZM, Yu ZJ, Song K, et al. Rutin inhibits quorum sensing, biofilm formation and virulence genes in avian pathogenic Escherichia coli. Microb Pathog. 2018; 119: 54–9. Available at: [https://doi.org/10.1016/J.MICPATH.2018.04.007].
Harada T, Akiyama Y, Kurashima A, Nagai H, Tsuyuguchi K, Fujii T, et al. Clinical and Microbiological Differences between Mycobacterium abscessus and Mycobacterium massiliense lung diseases. J Clin Microbiol. 2012; 50(11): 3556-61. Available at: [https://doi.org/10.1128/JCM.01175-12].
Deepika MS, Thangam R, Sakthidhasan P, Arun S, Sivasubramanian S, Thirumurugan R. Combined effect of a natural flavonoid rutin from Citrus sinensis and conventional antibiotic gentamicin on Pseudomonas aeruginosa biofilm formation. Food Control. 2018; 90: 282-94. Available at: [https://doi.org/10.1016/J.FOODCONT.2018.02.044].
MSc. Maiara Oliveira Jantsch
Universidade Federal de Santa Maria, UFSM, Departamento de Análises Clínicas e Toxicológicas, Avenida Roraima, nº 1000, Cidade Universitária, Bairro Camobi, CEP: 97105-900, Santa Maria, RS, Brasil. https://orcid.org/0000-0002-1881-6759