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1.
Front Cell Infect Microbiol ; 13: 1187831, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37333850

RESUMO

The morbidity and mortality of invasive fungal infections are rising gradually. In recent years, fungi have quietly evolved stronger defense capabilities and increased resistance to antibiotics, posing huge challenges to maintaining physical health. Therefore, developing new drugs and strategies to combat these invasive fungi is crucial. There are a large number of microorganisms in the intestinal tract of mammals, collectively referred to as intestinal microbiota. At the same time, these native microorganisms co-evolve with their hosts in symbiotic relationship. Recent researches have shown that some probiotics and intestinal symbiotic bacteria can inhibit the invasion and colonization of fungi. In this paper, we review the mechanism of some intestinal bacteria affecting the growth and invasion of fungi by targeting the virulence factors, quorum sensing system, secreting active metabolites or regulating the host anti-fungal immune response, so as to provide new strategies for resisting invasive fungal infection.


Assuntos
Micoses , Animais , Humanos , Micoses/tratamento farmacológico , Fungos , Simbiose , Intestinos , Bactérias , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Mamíferos
2.
Virulence ; 14(1): 2230009, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37367101

RESUMO

Candidiasis caused by Candida albicans infection has long been a serious human health problem. The pathogenicity of C. albicans is mainly due to its virulence factors, which are novel targets of antifungal drugs for low risk of resistance development. In this study, we identified a maleimide compound [1-(4-methoxyphenyl)-1hydro-pyrrole-2,5-dione, MPD] that exerts effective anti-virulence activity. It could inhibit the process of adhesion, filamentation, and biofilm formation in C. albicans. In addition, it exhibited low cytotoxicity, hemolytic activity, and drug resistance development. Moreover, in Galleria mellonella-C. albicans (in vivo) infection model, the survival time of infected larvae was significantly prolonged under the treatment of MPD. Further, mechanism research revealed that MPD increased farnesol secretion by upregulating the expression of Dpp3. The increased farnesol inhibited the activity of Cdc35, which then decreased the intracellular cAMP content resulting in the inhibition of virulence factors via the Ras1-cAMP-Efg1 pathway. In all, this study evaluated the inhibitory effect of MPD on various virulence factors of C. albicans and identified the underlying mechanisms. This suggests a potential application of MPD to overcome fungal infections in clinics.


Assuntos
Candida albicans , Candidíase , Animais , Humanos , Candida albicans/metabolismo , Fatores de Virulência/metabolismo , Farneseno Álcool/farmacologia , Candidíase/microbiologia , Antifúngicos/uso terapêutico , Maleimidas/metabolismo , Maleimidas/farmacologia , Maleimidas/uso terapêutico , Biofilmes , Hifas
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