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2021
Assad, Beatriz M.; Savi, Daiani C.; Biscaia, Stellee M. P.; Mayrhofer, Bárbara F.; Iantas, Jucelia; Mews, Mathias; Oliveira, Jaqueline C.; Trindade, Edvaldo S.; Glienke, Chirlei
In: Microbiological Research, vol. 248, 2021, ISSN: 09445013.
Abstract | Links | BibTeX | Tags: Actinobacteria, Antimicrobial, Antitumoral, Endophytes, Wetland Pantanal
@article{Assad2021,
title = {Endophytic actinobacteria of Hymenachne amplexicaulis from the Brazilian Pantanal wetland produce compounds with antibacterial and antitumor activities},
author = {Beatriz M. Assad and Daiani C. Savi and Stellee M. P. Biscaia and Bárbara F. Mayrhofer and Jucelia Iantas and Mathias Mews and Jaqueline C. Oliveira and Edvaldo S. Trindade and Chirlei Glienke},
doi = {10.1016/J.MICRES.2021.126768},
issn = {09445013},
year = {2021},
date = {2021-01-01},
journal = {Microbiological Research},
volume = {248},
publisher = {Elsevier GmbH},
abstract = {The increase in the number of deaths from infections caused by multidrug-resistant bacteria and cancer diseases highlights the need for new molecules with biological activity. Actinobacteria represent a potential source of new compounds, as these microorganisms have already produced a great diversity of clinically employed antibiotics. Endophytes from unexplored biomes, such as the Pantanal (the largest wetland in the world), can be a source of new molecules. Hymenachne amplexicaulis is among the unexplored native plants of the Pantanal in terms of its endophytic community. This plant is considered a weed in other countries due to its ability to adapt and compete with native plants, and there is evidence to suggest that the endophytic community of H. amplexicaulis plays an important role in this competitiveness. To explore its therapeutic potential, the present study isolated, identified (using partial sequence of the 16S rDNA) and bioprospected H. amplexicaulis endophytic actinobacteria. Ten isolates belonging to the genera Streptomyces, Microbispora, Leifsonia, and Verrucosispora were obtained from root fragments. The susceptibility profile of the isolates to the different classes of antibiotics was evaluated, with 80 % of the isolates showing resistance to the antibiotics Nalidixic Acid, Ampicillin, Chloramphenicol, Oxacillin, and Rifampicin. To assess antibacterial and antitumor activities, methanolic extracts were obtained by fermentation in SG culture medium at 36 °C at 180 rpm for 10 days. The extract produced from the S. albidoflavus CMRP4854 isolate was the only one to show activity against the Gram-negative bacterium Acinetobacter baumanii. Due to the great clinical importance of this pathogen and the difficulty in obtaining active compounds against it, the CMRP4854 isolate should be further investigated for the identification of active compounds and mode of action. We also emphasize the results obtained by the extract of the isolates Streptomyces albidoflavus CMRP4852 and Verrucosispora sp. CMRP4860 that presented antibacterial effect against Methicilin-resistant Staphylococcus aureus (MRSA) (MIC: 1.5 μg/mL and 13 μg/mL, respectively) and Vancomycin-resistant Enterococcus (VRE) (MIC: 40 μg/mL for both extracts). Extracts (200 μg/mL) of these two endophytes also showed selective cytotoxicity action against murine B16-F10 melanoma cells. However, the CMRP4852 extract also affected the density of normal cells. Due to these results, the crude extract of isolate CMRP4860 Verrucosispora sp., which was the only one that presented cytotoxicity and reduced cell density only in tumor cells, was selected for subsequent analysis involving scale-up fermentation of the CMRP4860 resulting in 9 fractions that were tested against both bacteria and tumor cells, with particular fractions showing promise and meriting further investigation. Taken together, the results of this study not only show for the first time that the endophytic community of H. amplexicaulis actinobacteria can produce secondary metabolites that potentially possess important antibacterial and cytotoxic properties, but also reinforce the pressing need to conserve biomes such as the Brazilian Pantanal.},
keywords = {Actinobacteria, Antimicrobial, Antitumoral, Endophytes, Wetland Pantanal},
pubstate = {published},
tppubtype = {article}
}
The increase in the number of deaths from infections caused by multidrug-resistant bacteria and cancer diseases highlights the need for new molecules with biological activity. Actinobacteria represent a potential source of new compounds, as these microorganisms have already produced a great diversity of clinically employed antibiotics. Endophytes from unexplored biomes, such as the Pantanal (the largest wetland in the world), can be a source of new molecules. Hymenachne amplexicaulis is among the unexplored native plants of the Pantanal in terms of its endophytic community. This plant is considered a weed in other countries due to its ability to adapt and compete with native plants, and there is evidence to suggest that the endophytic community of H. amplexicaulis plays an important role in this competitiveness. To explore its therapeutic potential, the present study isolated, identified (using partial sequence of the 16S rDNA) and bioprospected H. amplexicaulis endophytic actinobacteria. Ten isolates belonging to the genera Streptomyces, Microbispora, Leifsonia, and Verrucosispora were obtained from root fragments. The susceptibility profile of the isolates to the different classes of antibiotics was evaluated, with 80 % of the isolates showing resistance to the antibiotics Nalidixic Acid, Ampicillin, Chloramphenicol, Oxacillin, and Rifampicin. To assess antibacterial and antitumor activities, methanolic extracts were obtained by fermentation in SG culture medium at 36 °C at 180 rpm for 10 days. The extract produced from the S. albidoflavus CMRP4854 isolate was the only one to show activity against the Gram-negative bacterium Acinetobacter baumanii. Due to the great clinical importance of this pathogen and the difficulty in obtaining active compounds against it, the CMRP4854 isolate should be further investigated for the identification of active compounds and mode of action. We also emphasize the results obtained by the extract of the isolates Streptomyces albidoflavus CMRP4852 and Verrucosispora sp. CMRP4860 that presented antibacterial effect against Methicilin-resistant Staphylococcus aureus (MRSA) (MIC: 1.5 μg/mL and 13 μg/mL, respectively) and Vancomycin-resistant Enterococcus (VRE) (MIC: 40 μg/mL for both extracts). Extracts (200 μg/mL) of these two endophytes also showed selective cytotoxicity action against murine B16-F10 melanoma cells. However, the CMRP4852 extract also affected the density of normal cells. Due to these results, the crude extract of isolate CMRP4860 Verrucosispora sp., which was the only one that presented cytotoxicity and reduced cell density only in tumor cells, was selected for subsequent analysis involving scale-up fermentation of the CMRP4860 resulting in 9 fractions that were tested against both bacteria and tumor cells, with particular fractions showing promise and meriting further investigation. Taken together, the results of this study not only show for the first time that the endophytic community of H. amplexicaulis actinobacteria can produce secondary metabolites that potentially possess important antibacterial and cytotoxic properties, but also reinforce the pressing need to conserve biomes such as the Brazilian Pantanal.
2019
Tonial, Fabiana; Bertol, Charise D.; Maia, Beatriz H. L. N. Sales; Figueiredo, Josiane A. G.; Guerra, Kielli C. F.; Glienke, Chirlei
Secondary Metabolite Produced by Diaporthe terebinthifolli LGMF658 – Bioactivity and Chemical Structure Relationship Journal Article
In: Current Bioactive Compounds, vol. 16, iss. 7, pp. 1103-1107, 2019, ISSN: 15734072.
Abstract | Links | BibTeX | Tags: Antimicrobial, Bioprospection, double bond, microdilution, verbanol, verbenol
@article{Tonial2019,
title = {Secondary Metabolite Produced by Diaporthe terebinthifolli LGMF658 – Bioactivity and Chemical Structure Relationship},
author = {Fabiana Tonial and Charise D. Bertol and Beatriz H. L. N. Sales Maia and Josiane A. G. Figueiredo and Kielli C. F. Guerra and Chirlei Glienke},
doi = {10.2174/1573407215666191108092008},
issn = {15734072},
year = {2019},
date = {2019-01-01},
journal = {Current Bioactive Compounds},
volume = {16},
issue = {7},
pages = {1103-1107},
publisher = {Bentham Science Publishers},
abstract = {© 2020, Bentham Science Publishers. All rights reserved. Background: Motivated by the need for bioprospecting new drug studies have revealed a variety of secondary metabolites with biological activity. In particular, antimicrobial research confronts the growing reality of resistance of microorganisms to currently available drugs. Modifications in the chemical structure of secondary metabolites may be important in the development of a product to improve the efficacy of these compounds. Being cognizant of the fact that modifications in the chemical structure could enhance the biological activity and improve the compound characteristics for the development of a product, the present study aimed to verify, if there is the possibility of a significant difference in the bioactivity of verbanol in relation to verbenol. Methods: The biological activity was evaluated by agar diffusion assay and microdilution. Results: Verbanol is a bioactive secondary metabolite produced by the endophytic fungus Diaporthe terebinthifolli LGMF658. This compound has bactericidal activity against Staphylococcus aureus and fungicide against Candida albicans according to the microdilution assay. Discussion: In contrast, verbenol, a byproduct of verbanol, did not control the development of the bacterium and showed fungistatic activity against yeast. Conclusion: The results demonstrated that the presence of the double bond, which increased the polarity of the compound, reduced its bioactivity, corroborating with other studies that report the importance of lipophilicity for antimicrobial action.},
keywords = {Antimicrobial, Bioprospection, double bond, microdilution, verbanol, verbenol},
pubstate = {published},
tppubtype = {article}
}
© 2020, Bentham Science Publishers. All rights reserved. Background: Motivated by the need for bioprospecting new drug studies have revealed a variety of secondary metabolites with biological activity. In particular, antimicrobial research confronts the growing reality of resistance of microorganisms to currently available drugs. Modifications in the chemical structure of secondary metabolites may be important in the development of a product to improve the efficacy of these compounds. Being cognizant of the fact that modifications in the chemical structure could enhance the biological activity and improve the compound characteristics for the development of a product, the present study aimed to verify, if there is the possibility of a significant difference in the bioactivity of verbanol in relation to verbenol. Methods: The biological activity was evaluated by agar diffusion assay and microdilution. Results: Verbanol is a bioactive secondary metabolite produced by the endophytic fungus Diaporthe terebinthifolli LGMF658. This compound has bactericidal activity against Staphylococcus aureus and fungicide against Candida albicans according to the microdilution assay. Discussion: In contrast, verbenol, a byproduct of verbanol, did not control the development of the bacterium and showed fungistatic activity against yeast. Conclusion: The results demonstrated that the presence of the double bond, which increased the polarity of the compound, reduced its bioactivity, corroborating with other studies that report the importance of lipophilicity for antimicrobial action.
2018
Nazaré, Ana Carolina; Polaquini, Carlos Roberto; Cavalca, Lúcia Bonci; Anselmo, Daiane Bertholin; Saiki, Marilia Freitas Calmon; Monteiro, Diego Alves; Zielinska, Aleksandra; Rahal, Paula; Gomes, Eleni; Scheffers, Dirk Jan; Ferreira, Henrique; Regasini, Luis Octavio
Design of Antibacterial Agents: Alkyl Dihydroxybenzoates against Xanthomonas citri subsp. citri Journal Article
In: International Journal of Molecular Sciences 2018, Vol. 19, Page 3050, vol. 19, iss. 10, pp. 3050, 2018, ISSN: 1422-0067.
Abstract | Links | BibTeX | Tags: Antimicrobial, Citrus canker, membrane disruption, phenolic acids, plant disease
@article{nokey,
title = {Design of Antibacterial Agents: Alkyl Dihydroxybenzoates against Xanthomonas citri subsp. citri},
author = {Ana Carolina Nazaré and Carlos Roberto Polaquini and Lúcia Bonci Cavalca and Daiane Bertholin Anselmo and Marilia Freitas Calmon Saiki and Diego Alves Monteiro and Aleksandra Zielinska and Paula Rahal and Eleni Gomes and Dirk Jan Scheffers and Henrique Ferreira and Luis Octavio Regasini},
url = {https://www.mdpi.com/1422-0067/19/10/3050/htm https://www.mdpi.com/1422-0067/19/10/3050},
doi = {10.3390/IJMS19103050},
issn = {1422-0067},
year = {2018},
date = {2018-01-01},
journal = {International Journal of Molecular Sciences 2018, Vol. 19, Page 3050},
volume = {19},
issue = {10},
pages = {3050},
publisher = {Multidisciplinary Digital Publishing Institute},
abstract = {Xanthomonas citri subsp. citri (Xcc) causes citrus canker, affecting sweet orange-producing areas around the world. The current chemical treatment available for this disease is based on cupric compounds. For this reason, the objective of this study was to design antibacterial agents. In order to do this, we analyzed the anti-Xcc activity of 36 alkyl dihydroxybenzoates and we found 14 active compounds. Among them, three esters with the lowest minimum inhibitory concentration values were selected; compounds 4 (52 μM), 16 (80 μM) and 28 (88 μM). Our study demonstrated that alkyl dihydroxybenzoates cause a delay in the exponential phase. The permeability capacity of alkyl dihydroxybenzoates in a quarter of MIC was compared to nisin (positive control). Compound 28 was the most effective (93.8), compared to compound 16 (41.3) and compound 4 (13.9) by percentage values. Finally, all three compounds showed inhibition of FtsZ GTPase activity, and promoted changes in protofilaments, leading to depolymerization, which prevents bacterial cell division. In conclusion, heptyl dihydroxybenzoates (compounds 4, 16 and 28) are promising anti-Xcc agents which may serve as an alternative for the control of citrus canker.},
keywords = {Antimicrobial, Citrus canker, membrane disruption, phenolic acids, plant disease},
pubstate = {published},
tppubtype = {article}
}
Xanthomonas citri subsp. citri (Xcc) causes citrus canker, affecting sweet orange-producing areas around the world. The current chemical treatment available for this disease is based on cupric compounds. For this reason, the objective of this study was to design antibacterial agents. In order to do this, we analyzed the anti-Xcc activity of 36 alkyl dihydroxybenzoates and we found 14 active compounds. Among them, three esters with the lowest minimum inhibitory concentration values were selected; compounds 4 (52 μM), 16 (80 μM) and 28 (88 μM). Our study demonstrated that alkyl dihydroxybenzoates cause a delay in the exponential phase. The permeability capacity of alkyl dihydroxybenzoates in a quarter of MIC was compared to nisin (positive control). Compound 28 was the most effective (93.8), compared to compound 16 (41.3) and compound 4 (13.9) by percentage values. Finally, all three compounds showed inhibition of FtsZ GTPase activity, and promoted changes in protofilaments, leading to depolymerization, which prevents bacterial cell division. In conclusion, heptyl dihydroxybenzoates (compounds 4, 16 and 28) are promising anti-Xcc agents which may serve as an alternative for the control of citrus canker.
Nazaré, Ana Carolina; Polaquini, Carlos Roberto; Cavalca, Lúcia Bonci; Anselmo, Daiane Bertholin; Saiki, Marilia Freitas Calmon; Monteiro, Diego Alves; Zielinska, Aleksandra; Rahal, Paula; Gomes, Eleni; Scheffers, Dirk Jan; Ferreira, Henrique; Regasini, Luis Octavio
Design of Antibacterial Agents: Alkyl Dihydroxybenzoates against Xanthomonas citri subsp. citri Journal Article
In: International Journal of Molecular Sciences 2018, Vol. 19, Page 3050, vol. 19, iss. 10, pp. 3050, 2018, ISSN: 1422-0067.
Abstract | Links | BibTeX | Tags: Antimicrobial, Citrus canker, membrane disruption, phenolic acids, plant disease
@article{nokey,
title = {Design of Antibacterial Agents: Alkyl Dihydroxybenzoates against Xanthomonas citri subsp. citri},
author = {Ana Carolina Nazaré and Carlos Roberto Polaquini and Lúcia Bonci Cavalca and Daiane Bertholin Anselmo and Marilia Freitas Calmon Saiki and Diego Alves Monteiro and Aleksandra Zielinska and Paula Rahal and Eleni Gomes and Dirk Jan Scheffers and Henrique Ferreira and Luis Octavio Regasini},
url = {https://www.mdpi.com/1422-0067/19/10/3050/htm https://www.mdpi.com/1422-0067/19/10/3050},
doi = {10.3390/IJMS19103050},
issn = {1422-0067},
year = {2018},
date = {2018-01-01},
journal = {International Journal of Molecular Sciences 2018, Vol. 19, Page 3050},
volume = {19},
issue = {10},
pages = {3050},
publisher = {Multidisciplinary Digital Publishing Institute},
abstract = {Xanthomonas citri subsp. citri (Xcc) causes citrus canker, affecting sweet orange-producing areas around the world. The current chemical treatment available for this disease is based on cupric compounds. For this reason, the objective of this study was to design antibacterial agents. In order to do this, we analyzed the anti-Xcc activity of 36 alkyl dihydroxybenzoates and we found 14 active compounds. Among them, three esters with the lowest minimum inhibitory concentration values were selected; compounds 4 (52 μM), 16 (80 μM) and 28 (88 μM). Our study demonstrated that alkyl dihydroxybenzoates cause a delay in the exponential phase. The permeability capacity of alkyl dihydroxybenzoates in a quarter of MIC was compared to nisin (positive control). Compound 28 was the most effective (93.8), compared to compound 16 (41.3) and compound 4 (13.9) by percentage values. Finally, all three compounds showed inhibition of FtsZ GTPase activity, and promoted changes in protofilaments, leading to depolymerization, which prevents bacterial cell division. In conclusion, heptyl dihydroxybenzoates (compounds 4, 16 and 28) are promising anti-Xcc agents which may serve as an alternative for the control of citrus canker.},
keywords = {Antimicrobial, Citrus canker, membrane disruption, phenolic acids, plant disease},
pubstate = {published},
tppubtype = {article}
}
Xanthomonas citri subsp. citri (Xcc) causes citrus canker, affecting sweet orange-producing areas around the world. The current chemical treatment available for this disease is based on cupric compounds. For this reason, the objective of this study was to design antibacterial agents. In order to do this, we analyzed the anti-Xcc activity of 36 alkyl dihydroxybenzoates and we found 14 active compounds. Among them, three esters with the lowest minimum inhibitory concentration values were selected; compounds 4 (52 μM), 16 (80 μM) and 28 (88 μM). Our study demonstrated that alkyl dihydroxybenzoates cause a delay in the exponential phase. The permeability capacity of alkyl dihydroxybenzoates in a quarter of MIC was compared to nisin (positive control). Compound 28 was the most effective (93.8), compared to compound 16 (41.3) and compound 4 (13.9) by percentage values. Finally, all three compounds showed inhibition of FtsZ GTPase activity, and promoted changes in protofilaments, leading to depolymerization, which prevents bacterial cell division. In conclusion, heptyl dihydroxybenzoates (compounds 4, 16 and 28) are promising anti-Xcc agents which may serve as an alternative for the control of citrus canker.