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1.
Artigo em Inglês | MEDLINE | ID: mdl-28955453

RESUMO

BACKGROUND: The need for new antibiotic drugs increases as pathogenic microorganisms continue to develop resistance against current antibiotics. We obtained samples from Antarctica as part of a search for new antimicrobial metabolites derived from filamentous fungi. This terrestrial environment near the South Pole is hostile and extreme due to a sparsely populated food web, low temperatures, and insufficient liquid water availability. We hypothesize that this environment could cause the development of fungal defense or survival mechanisms not found elsewhere. RESULTS: We isolated a strain of Penicillium nalgiovense Laxa from a soil sample obtained from an abandoned penguin's nest. Amphotericin B was the only metabolite secreted from Penicillium nalgiovense Laxa with noticeable antimicrobial activity, with minimum inhibitory concentration of 0.125 µg/mL against Candida albicans. This is the first time that amphotericin B has been isolated from an organism other than the bacterium Streptomyces nodosus. In terms of amphotericin B production, cultures on solid medium proved to be a more reliable and favorable choice compared to liquid medium. CONCLUSIONS: These results encourage further investigation of the many unexplored sampling sites characterized by extreme conditions, and confirm filamentous fungi as potential sources of metabolites with antimicrobial activity.

2.
PLoS One ; 9(4): e93685, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24705440

RESUMO

Aspergillus fumigatus is the most common causative agent of mold diseases in humans, giving rise to life-threatening infections in immunocompromised individuals. One of its secreted metabolites is gliotoxin, a toxic antimicrobial agent. The aim of this study was to determine whether the presence of pathogen-associated molecular patterns in broth cultures of A. fumigatus could induce gliotoxin production. Gliotoxin levels were analyzed by ultra-performance liquid chromatography and mass spectrometry. The presence of a bacteria-derived lipopolysaccharide, peptidoglycan, or lipoteichoic acid in the growth media at a concentration of 5 µg/ml increased the gliotoxin concentration in the media by 37%, 65%, and 35%, respectively. The findings reveal a correlation between the concentrations of pathogen-associated molecular patterns and gliotoxin secretion. This shows that there is a yet uncharacterized detection system for such compounds within fungi. Inducing secondary metabolite production by such means in fungi is potentially relevant for drug discovery research. Our results also give a possible explanation for the increased virulence of A. fumigatus during bacterial co-infection, one that is important for the transition from colonization to invasiveness in this pulmonary disease.


Assuntos
Aspergillus fumigatus/metabolismo , Gliotoxina/metabolismo , Aspergillus fumigatus/patogenicidade , Cromatografia Líquida de Alta Pressão , Meios de Cultura/química , Lipopolissacarídeos/análise , Lipopolissacarídeos/farmacologia , Espectrometria de Massas , Peptidoglicano/análise , Peptidoglicano/farmacologia , Ácidos Teicoicos/análise , Ácidos Teicoicos/farmacologia , Virulência
3.
Artigo em Inglês | MEDLINE | ID: mdl-22957125

RESUMO

BACKGROUND: Filamentous fungi are well known for their production of substances with antimicrobial activities, several of which have formed the basis for the development of new clinically important antimicrobial agents. Recently, environments polluted with extraordinarily high levels of antibiotics have been documented, leading to strong selection pressure on local sentinel bacterial communities. In such microbial ecosystems, where multidrug-resistant bacteria are likely to thrive, it is possible that certain fungal antibiotics have become less efficient, thus encouraging alternative strategies for fungi to compete with bacteria. METHODS: In this study, sediment of a highly antibiotic-contaminated Indian river was sampled in order to investigate the presence of cultivable filamentous fungi and their ability to produce substances with antimicrobial activity. RESULTS: Sixty one strains of filamentous fungi, predominantly various Aspergillus spp. were identified. The majority of the Aspergillus strains displayed antimicrobial activity against methicillin-resistant Staphylococcus aureus, extended-spectrum beta-lactamase-producing Escherichia coli, vancomycin-resistant Enterococcus faecalis and Candida albicans. Bioassay-guided isolation of the secondary metabolites of A. fumigatus led to the identification of gliotoxin. CONCLUSION: This study demonstrated proof of principle of using bioassay-guided isolation for finding bioactive molecules.

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