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Anti-Acanthamoeba castellanii activity of alkaloid-enriched extracts and lycorine from the Amaryllidaceae species
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Rosa, Maressa Dietrich

; Andrade, Jean Paulo de

; Costa, Adriana Oliveira

; Conti, Raphael

; Bastida, Jaume

; Borges, Warley de Souza

; Furst, Cinthia

Brazilian Journal of Pharmaceutical Sciences

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2022, Volume 58 elocation e20459

Resumo: En | Texto: En | PDF: En

Abstract Free-living amoebae of the genus Acanthamoeba are the causative agents of granulomatous encephalitis and keratitis, severe human infections. Bioactive compounds from plants are recognized as an alternative source for the development of new drugs. The Amaryllidaceae is a botanical family able to synthesize a very specific and consistent group of biologically active isoquinoline-like alkaloids. The alkaloidal fractions from the Brazilian species Hippeastrum canastrense, H. diniz-cruziae, H. puniceum, and Crinum x amabile, along with the alkaloid lycorine, were investigated against Acanthamoeba castellanii. The in vitro assays were performed with distinct concentrations of lycorine and alkaloidal fractions, while the cell viability was evaluated by the MTT method upon MDCK cells. Chlorhexidine 0.02% was used as the positive control. The effect of alkaloid fractions was concentration dependent, and 2000 μg mL-1 of H. canastrense and H. diniz-cruziae provided a 100% inhibition. At concentrations of 250, 500, and 1000 μg mL-1, the H. diniz-cruziae alkaloidal fraction showed the lowest cytotoxic effect (5%-7%) and remarkable anti-amoebic activity, demonstrating values of IC50 285.61 μg mL-1, low cytotoxicity (5%-7%), and selectivity index (7.0). Taken together, the results are indicative of the great potential that the alkaloids from H. diniz-cruziae have as new candidates for anti-amoebicidal compounds.

https://doi.org/10.1590/s2175-97902022e20459

Epidemiologia e desfecho dos pacientes de alto risco cirúrgico admitidos em unidades de terapia intensiva no Brasil
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Silva Júnior, João Manoel

; Chaves, Renato Carneiro de Freitas

; Corrêa, Thiago Domingos

; Assunção, Murillo Santucci Cesar de

; Katayama, Henrique Tadashi

; Bosso, Fabio Eduardo

; Amendola, Cristina Prata

; Serpa Neto, Ary

; Malbouisson, Luiz Marcelo Sá

; Oliveira, Neymar Elias de

; Veiga, Viviane Cordeiro

; Rojas, Salomón Soriano Ordinola

; Postalli, Natalia Fioravante

; Alvarisa, Thais Kawagoe

; Lucena, Bruno Melo Nobrega de

; Oliveira, Raphael Augusto Gomes de

; Sanches, Luciana Coelho

; Silva, Ulysses Vasconcellos de Andrade e

; Nassar Junior, Antonio Paulo

; Réa-Neto, Álvaro

; Amaral, Alexandre

; Teles, José Mário

; Freitas, Flávio Geraldo Rezende de

; Bafi, Antônio Tonete

; Pacheco, Eduardo Souza

; Ramos, Fernando José

; Vieira Júnior, José Mauro

; Pereira, Maria Augusta Santos Rahe

; Schwerz, Fábio Sartori

; Menezes, Giovanna Padoa de

; Magalhães, Danielle Dourado

; Castro, Cristine Pilati Pileggi

; Henrich, Sabrina Frighetto

; Toledo, Diogo Oliveira

; Parra, Bruna Fernanda Camargo Silva

; Dias, Fernando Suparregui

; Zerman, Luiza

; Formolo, Fernanda

; Nobrega, Marciano de Sousa

; Piras, Claudio

; Piras, Stéphanie de Barros

; Conti, Rodrigo

; Bittencourt, Paulo Lisboa

; D’Oliveira, Ricardo Azevedo Cruz

; Estrela, André Ricardo de Oliveira

; Oliveira, Mirella Cristine de

; Reese, Fernanda Baeumle

; Motta Júnior, Jarbas da Silva

; Câmara, Bruna Martins Dzivielevski da

; David-João, Paula Geraldes

; Tannous, Luana Alves

; Chaiben, Viviane Bernardes de Oliveira

; Miranda, Lorena Macedo Araújo

; Brasil, José Arthur dos Santos

; Deucher, Rafael Alexandre de Oliveira

; Ferreira, Marcos Henrique Borges

; Vilela, Denner Luiz

; Almeida, Guilherme Cincinato de

; Nedel, Wagner Luis

; Passos, Matheus Golenia dos

; Marin, Luiz Gustavo

; Oliveira Filho, Wilson de

; Coutinho, Raoni Machado

; Oliveira, Michele Cristina Lima de

; Friedman, Gilberto

; Meregalli, André

; Höher, Jorge Amilton

; Soares, Afonso José Celente

; Lobo, Suzana Margareth Ajeje

Revista Brasileira de Terapia Intensiva

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Mar 2020, Volume 32 Nº 1 Páginas 17 - 27

Resumo: Pt En | Texto: Pt En | PDF: Pt | PDF: En

RESUMO Objetivo: Definir o perfil epidemiológico e os principais determinantes de morbimortalidade dos pacientes cirúrgicos não cardíacos de alto risco no Brasil. Métodos: Estudo prospectivo, observacional e multicêntrico. Todos os pacientes cirúrgicos não cardíacos admitidos nas unidades de terapia intensiva, ou seja, considerados de alto risco, no período de 1 mês, foram avaliados e acompanhados diariamente por, no máximo, 7 dias na unidade de terapia intensiva, para determinação de complicações. As taxas de mortalidade em 28 dias de pós-operatório, na unidade de terapia intensiva e hospitalar foram avaliadas. Resultados: Participaram 29 unidades de terapia intensiva onde foram realizadas cirurgias em 25.500 pacientes, dos quais 904 (3,5%) de alto risco (intervalo de confiança de 95% - IC95% 3,3% - 3,8%), tendo sido incluídos no estudo. Dos pacientes envolvidos, 48,3% eram de unidades de terapia intensiva privadas e 51,7% de públicas. O tempo de internação na unidade de terapia intensiva foi de 2,0 (1,0 - 4,0) dias e hospitalar de 9,5 (5,4 - 18,6) dias. As taxas de complicações foram 29,9% (IC95% 26,4 - 33,7) e mortalidade em 28 dias pós-cirurgia 9,6% (IC95% 7,4 - 12,1). Os fatores independentes de risco para complicações foram Simplified Acute Physiology Score 3 (SAPS 3; razão de chance − RC = 1,02; IC95% 1,01 - 1,03) e Sequential Organ Failure Assessment Score (SOFA) da admissão na unidade de terapia intensiva (RC =1,17; IC95% 1,09 - 1,25), tempo de cirurgia (RC = 1,001; IC95% 1,000 - 1,002) e cirurgias de emergências (RC = 1,93; IC95% 1,10 - 3,38). Em adição, foram associados com mortalidade em 28 dias idade (RC = 1,032; IC95% 1,011 - 1,052) SAPS 3 (RC = 1,041; IC95% 1,107 - 1,279), SOFA (RC = 1,175; IC95% 1,069 - 1,292) e cirurgias emergenciais (RC = 2,509; IC95% 1,040 - 6,051). Conclusão: Pacientes com escores prognósticos mais elevados, idosos, tempo cirúrgico e cirurgias emergenciais estiveram fortemente associados a maior mortalidade em 28 dias e mais complicações durante permanência em unidade de terapia intensiva.

ABSTRACT Objective: To define the epidemiological profile and the main determinants of morbidity and mortality in noncardiac high surgical risk patients in Brazil. Methods: This was a prospective, observational and multicenter study. All noncardiac surgical patients admitted to intensive care units, i.e., those considered high risk, within a 1-month period were evaluated and monitored daily for a maximum of 7 days in the intensive care unit to determine complications. The 28-day postoperative, intensive care unit and hospital mortality rates were evaluated. Results: Twenty-nine intensive care units participated in the study. Surgeries were performed in 25,500 patients, of whom 904 (3.5%) were high-risk (95% confidence interval - 95%CI 3.3% - 3.8%) and were included in the study. Of the participating patients, 48.3% were from private intensive care units, and 51.7% were from public intensive care units. The length of stay in the intensive care unit was 2.0 (1.0 - 4.0) days, and the length of hospital stay was 9.5 (5.4 - 18.6) days. The complication rate was 29.9% (95%CI 26.4 - 33.7), and the 28-day postoperative mortality rate was 9.6% (95%CI 7.4 - 12.1). The independent risk factors for complications were the Simplified Acute Physiology Score 3 (SAPS 3; odds ratio - OR = 1.02; 95%CI 1.01 - 1.03) and Sequential Organ Failure Assessment Score (SOFA) on admission to the intensive care unit (OR = 1.17; 95%CI 1.09 - 1.25), surgical time (OR = 1.001, 95%CI 1.000 - 1.002) and emergency surgeries (OR = 1.93, 95%CI, 1.10 - 3.38). In addition, there were associations with 28-day mortality (OR = 1.032; 95%CI 1.011 - 1.052), SAPS 3 (OR = 1.041; 95%CI 1.107 - 1.279), SOFA (OR = 1.175, 95%CI 1.069 - 1.292) and emergency surgeries (OR = 2.509; 95%CI 1.040 - 6.051). Conclusion: Higher prognostic scores, elderly patients, longer surgical times and emergency surgeries were strongly associated with higher 28-day mortality and more complications during the intensive care unit stay.

https://doi.org/10.5935/0103-507x.20200005 1048 downloads

Identifying New Isatin Derivatives with GSK-3β Inhibition Capacity through Molecular Docking and Bioassays
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Britto, Karolinni B.

; Francisco, Carla S.

; Ferreira, Débora

; Borges, Bárbara J. P.

; Conti, Raphael

; Profeti, Demetrius

; Rodrigues, Ligia R.

; Lacerda Jr., Valdemar

; Morais, Pedro A. B.

; Borges, Warley S.

Journal of the Brazilian Chemical Society

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Mar 2020, Volume 31 Nº 3 Páginas 476 - 487

Resumo: En | Texto: En | PDF: En

The semi-synthesis of 11 isatin derivatives was achieved through bimolecular nucleophilic substitution and click chemistry. Seven new compounds were obtained. All chemical structures were determined by infrared spectroscopy (IR), nuclear magnetic resonance spectrometry (NMR) and high-resolution mass spectrometry (HRMS) data. These derivatives were evaluated for their anti-GSK-3b activity and all isatin derivatives (N-alkyl and 1,2,3-triazolic) exhibited strong inhibitory activity, with 2b and 4h exhibiting remarkable potency. In addition, docking studies were performed with 2b and 2e models to unravel the molecular mechanism underlying the polar interactions on the GSK-3b ATP-binding site.

https://doi.org/10.21577/0103-5053.20190206 371 downloads

In vitro Antiplasmodial Activities of Alkaloids Isolated from Roots of Worsleya procera (Lem.) Traub (Amaryllidaceae)
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Gonring-Salarini, Karla L.

; Conti, Raphael

; Andrade, Jean Paulo de

; Borges, Bárbara Juliana P.

; Aguiar, Anna Caroline C.

; Souza, Juliana O. de

; Zanini, Camila L.

; Oliva, Glaucius

; Tenorio, Juan Carlos

; Ellena, Javier

; Bastida, Jaume

; Guido, Rafael V. C.

; Borges, Warley de S.

Journal of the Brazilian Chemical Society

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Ago 2019, Volume 30 Nº 8 Páginas 1624 - 1633

Resumo: En | Texto: En | PDF: En

A combined phytochemical, crystallographic and biological study of Worsleya procera roots was performed. Fifteen alkaloids were identified by gas chromatography mass spectrometry (GC-MS) and seven of them were isolated. The structures of the alkaloids were elucidated by spectroscopic methods, and a detailed crystallographic study of tazettine was carried out. The isolated alkaloids and the obtained extracts were tested in vitro against Plasmodium falciparum (3D7 and K1 strains) and human hepatocarcinoma cells (HepG2) to assess their antiplasmodial and cytotoxic effects, respectively. One of the isolated alkaloid derivatives, lycorine, exhibited antiplasmodial activity against both sensitive (3D7) and resistant (K1) parasite strains in the low micromolar range (half-maximal sample inhibitory concentration (IC50) values of 2.5 and 3.1 µM, respectively) and displayed a low cytotoxicity profile, with a selectivity index greater than 100. Our findings indicate that lycorine is a hit for antimalarial drug discovery.

https://doi.org/10.21577/0103-5053.20190061 567 downloads

Defensive Interactions in Soccer Small-Sided Games: an Integrated Approach Between the Fundamental Tactical Principles and the Social Network Analysis
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Praça, Gibson Moreira

; Sousa, Raphael Brito e

; Bredt, Sarah da Glória Teles

; Clemente, Filipe Manuel

; Teoldo, Israel

; Castro, Henrique de Oliveira

; Costa, Gustavo De Conti Teixeira

; Moreira, Pedro Emílio Drumond

Revista Brasileira de Cineantropometria & Desempenho Humano

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Out 2018, Volume 20 Nº 5 Páginas 422 - 431

Resumo: Pt En | Texto: Pt En | PDF: Pt | PDF: En

Resumo Este estudo objetivou 1) apresentar uma nova análise das interações entre os princípios cobertura defensiva e contenção utilizando a Social Network Analysis (SNA); 2) comparar os padrões de cooperação defensiva apresentados por jogadores de diferentes categorias durante pequenos jogos (SSG) 3vs.3; 3) comparar o nível de prominência entre defensores, meio-campistas e atacantes entre duas categorias e dentro de uma mesma categoria. Vinte e oito atletas das categorias sub-13 (n=14) e sub-14 (n=14) de um clube participaram em pequenos jogos 3vs.3 para a análise dos princípios táticos defensivos. As interações defensivas foram consideradas quando ocorreu uma cobertura defensiva e uma contenção em um mesmo intervalo de tempo. As análises macro (density e clustering coefficient) e micro (degree centrality, degree prestigie e page rank) foram utilizadas como medidas da SNA. Os resultados indicaram ausência de diferenças entre categorias para ambas as análises macro e micro. Meio campistas apresentaram maiores níveis de proeminência apenas na categoria sub-14 (p=0.004). Nós concluímos que atletas sub-13 e sub-14 não apresentam diferenças significativas entre si para os padrões de cooperação defensiva. Um maior conhecimento tático posicional obtido por meio da prática deliberada é crucial para o desenvolvimento de interações defensivas diferentes entre as posições, como mostrado pelas diferenças entre posições apenas na categoria sub-14.

Abstract This study aimed to 1) present a new analysis of the interactions between the tactical principles of defensive coverage and delay using the Social Network Analysis (SNA); 2) compare the defensive cooperation patterns presented by players of different categories during a 3vs.3 soccer small-sided games SSG; 3) compare the level of defensive prominence presented by defenders, midfielders, and forwards in 3vs.3 SSG within and between different categories. Twenty-eight soccer athletes from U-13 (n=14) and U-14 (n=14) categories of a sports club performed 3vs.3 SSG for the analysis of the defensive tactical principles. Defensive interactions were considered successful defensive coverage and a delay actions performed within the same time interval. Macro (density and clustering coefficient) and micro (degree centrality, degree prestige and page rank) analyses were used as SNA measures. Results indicated no significant differences between categories for the macro and micro analyses. Only in the U-14 category, midfielders presented higher prominence levels than the other playing positions (p=0.004). We concluded that U-13 and U-14 athletes are not different regarding defensive cooperation patterns. A higher positional tactical knowledge obtained through deliberate practice is essential to induce different defensive interactions between playing positions, as shown by significant differences only in the U-14 category.

https://doi.org/10.5007/1980-0037.2018v20n5p422 770 downloads

Antibacterial, antifungal and cytotoxic activities exhibited by endophytic fungi from the Brazilian marine red alga Bostrychia tenella (Ceramiales)
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Felício, Rafael de

; Pavão, Gabriel B.

; Oliveira, Ana Lígia L. de

; Erbert, Cíntia

; Conti, Raphael

; Pupo, Monica T.

; Furtado, Niege A.J.C.

; Ferreira, Elthon G.

; Costa-Lotufo, Letícia V.

; Young, Maria Cláudia M.

; Yokoya, Nair S.

; Debonsi, Hosana M.

Revista Brasileira de Farmacognosia

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Dez 2015, Volume 25 Nº 6 Páginas 641 - 650

Resumo: En | Texto: En | PDF: En

Abstract Marine environment is one of the most important sources regarding natural products research. Besides, marine microorganisms have been denominated as a talented natural source for discovery of new leads. Although the association of macroalgae and fungi has been described regarding ecological issues, there is a lack of studies about marine seaweed endophytic fungi. In this context, the goal of this study was to evaluate cytotoxic, antifungal and antibacterial activities of endophytic fungi isolated from the Brazilian marine seaweed Bostrychia tenella (J.V. Lamouroux) J. Agardh (Ceramiales, Rhodophyta). Forty-five endophytic microorganism strains were isolated from B. tenella. Crude extracts and organic fractions of ten selected strains were obtained after growth in rice medium. Samples were evaluated for cytotoxicity, antifungal and antibacterial assays. Penicillium strains showed positive results in a diversity of assays, and other five strains were active in at least one test. In addition, cytochalasin D was isolated from Xylaria sp. This alga is composed of a microbiological potential, since its endophytic strains exhibited remarkable biological properties. Moreover, cytochalasin D isolation has confirmed chemical potential of marine endophytic strains. This is the first study in which cultured fungi isolates from the Brazilian macroalga B. tenella were evaluated concerning biological properties. Results corroborated that this species could be a pharmaceutical source from marine environment. Furthermore, Acremonium implicatum is being firstly described as marine endophyte and Xylaria sp., Trichoderma atroviride and Nigrospora oryzae as marine seaweed endophytes. Thus, this work reports the first study relating detailed isolation, cultivation and biological evaluation (cytotoxic, antifungal and antibacterial) of endophytes Penicillium decaturense and P. waksmanii from the Brazilian marine red alga B. tenella. We are also reporting the isolation of cytochalasin D, a known antitumor and antibiotic compound, from Xylaria sp. strain. Despite widespread prevalence in terrestrial and marine habitats, this present work describes the first occurrence of cytochalasin D as a metabolite from marine seaweed endophyte.

https://doi.org/10.1016/j.bjp.2015.08.003 2375 downloads

Peritumoral infiltrate in the prognosis of epidermoid carcinoma of the oral cavity
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Affonso, Vivian Regina

; Montoro, José Raphael de Moura Campos

; Freitas, Luiz Carlos Conti de

; Saggioro, Fabiano Pinto

; Souza, Luiz de

; Mamede, Rui Celso Martins

Brazilian Journal of Otorhinolaryngology

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Ago 2015, Volume 81 Nº 4 Páginas 416 - 421

Resumo: Pt En | Texto: Pt En | PDF: Pt | PDF: En

INTRODUÇÃO: Pacientes com carcinoma epidermoide de cavidade oral mostram déficits em sua imunidade celular, que contribuem para o crescimento neoplásico. Assim, a atividade inflamatória, como resposta imunológica ao tumor, pode servir como fator prognóstico.OBJETIVOS: Avaliar a correlação entre o processo inflamatório peritumoral com as características clínicas dos pacientes, com a sobrevida e com o tempo livre de doença.MÉTODO: A amostra deste estudo foi composta por uma coorte retrospectiva de base hospitalar com pacientes submetidos à cirurgia para remoção de carcinoma epidermoide de cavidade oral. O infiltrado inflamatório presente nas lâminas foi avaliado semi quantitativamente, sendo dividido em processo inflamatório: menor e maior.RESULTADOS: Analisaram-se 57 amostras tumorais, com infiltrado de linfócitos, plasmócitos e histiócitos. O teste log-rank não mostrou significância para as curvas de sobrevida e de recidiva dos processos "inflamatório menor" e "inflamatório maior", p = 0,14 e p = 0,24, respectivamente. Observou-se associação direta da idade com o processo inflamatório (p = 0,04), e relação indireta entre o grau de diferenciação tumoral e o processo inflamatório (p = 0,01).CONCLUSÃO: O processo inflamatório peritumoral, embora relacionado com a diferenciação histológica, não pode ser considerado fator prognóstico de carcinoma epidermoide de cavidade oral, pois não se relaciona com sobrevida e tempo livre da doença.

INTRODUCTION: Patients with squamous cell carcinoma of the oral cavity present deficits in their cellular immunity that contribute to neoplastic growth. Thus, the inflammatory activity, such as the immunological response to the tumor, can be used as a prognostic factor.OBJECTIVES: To evaluate the correlation between peritumoral inflammation and clinical characteristics of the patients, survival, and the disease-free interval.METHODS: The study sample consisted of a retrospective hospital-based cohort of patients undergoing surgery for resection of oral cavity tumor. The inflammatory infiltrate on the slides was evaluated semi-quantitatively, and were divided into minor and major inflammatory processes.RESULTS: This study included 57 tumor samples, with infiltration of lymphocytes, plasma cells, and histiocytes. The log-rank test showed no significance for the survival curves and recurrence of the "minor inflammatory" and "major inflammatory" processes, with p = 0.14 and p = 0.24, respectively. A direct association between age and inflammation (p = 0.04) was observed, as well as an indirect association between the degree of tumor differentiation and inflammation (p = 0.01).CONCLUSION: Although associated with histological differentiation, the peritumoral inflammatory process cannot be considered a prognostic factor in squamous cell carcinoma of the oral cavity, as it is not related to survival and disease-free interval.

https://doi.org/10.1016/j.bjorl.2014.09.010 9278 downloads

Bioactive extracts and chemical constituents of two endophytic strains of Fusarium oxysporum
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Nascimento, Andréa M. do

; Conti, Raphael

; Turatti, Izabel C. C.

; Cavalcanti, Bruno C.

; Costa-Lotufo, Letícia V.

; Pessoa, Cláudia

; Moraes, Manoel O. de

; Manfrim, Viviane

; Toledo, Juliano S.

; Cruz, Angela K.

; Pupo, Mônica T.

Revista Brasileira de Farmacognosia

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Dez 2012, Volume 22 Nº 6 Páginas 1276 - 1281

Resumo: En | Texto: En | PDF: En

Ethyl acetate extracts of cultures grown in liquid Czapek and on solid rice media of the fungal endophyte Fusarium oxysporum SS46 isolated from the medicinal plant Smallanthus sonchifolius (Poepp.) H. Rob., Asteraceae, exhibited considerable cytotoxic activity when tested in vitro against human cancer cells. Chromatographic separation yielded anhydrofusarubin (1) and beauvericin (2) that were identified based on their ¹H and 13C NMR data. Compounds 1 and 2 showed the strongest cytotoxic activity against different cancer cell lines. Compound 2 also showed promising activity against Leishmania braziliensis. Hexanic extract of F. oxysporum SS50 grown on solid rice media also afforded a mixture of compounds that displayed cytotoxic activity against different cancer cell lines. Chemical analysis of the mixture of compounds, investigated by gas chromatography-mass spectrometry (GC-MS), showed that there was a predominance of methyl esters of fatty acids and alkanes.

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Analysis of 16S rRNA and mxaF genes reveling insights into Methylobacterium niche-specific plant association
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Dourado, Manuella Nóbrega

; Andreote, Fernando Dini

; Dini-Andreote, Francisco

; Conti, Raphael

; Araújo, Janete Magali

; Araújo, Welington Luiz

Genetics and Molecular Biology

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2012, Volume 35 Nº 1 Páginas 142 - 148

Resumo: En | Texto: En | PDF: En

The genus Methylobacterium comprises pink-pigmented facultative methylotrophic (PPFM) bacteria, known to be an important plant-associated bacterial group. Species of this group, described as plant-nodulating, have the dual capacity of producing cytokinin and enzymes, such as pectinase and cellulase, involved in systemic resistance induction and nitrogen fixation under specific plant environmental conditions. The aim hereby was to evaluate the phylogenetic distribution of Methylobacterium spp. isolates from different host plants. Thus, a comparative analysis between sequences from structural (16S rRNA) and functional mxaF (which codifies for a subunit of the enzyme methanol dehydrogenase) ubiquitous genes, was undertaken. Notably, some Methylobacterium spp. isolates are generalists through colonizing more than one host plant, whereas others are exclusively found in certain specific plant-species. Congruency between phylogeny and specific host inhabitance was higher in the mxaF gene than in the 16S rRNA, a possible indication of function-based selection in this niche. Therefore, in a first stage, plant colonization by Methylobacterium spp. could represent generalist behavior, possibly related to microbial competition and adaptation to a plant environment. Otherwise, niche-specific colonization is apparently impelled by the host plant.

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