RESUMO
Secretory phospholipase B1 (PLB1) and biofilms act as microbial virulence factors and play an important role in pulmonary cryptococcosis. This study aims to formulate the ethanolic extract of propolis-loaded niosomes (Nio-EEP) and evaluate the biological activities occurring during PLB1 production and biofilm formation of Cryptococcus neoformans. Some physicochemical characterizations of niosomes include a mean diameter of 270 nm in a spherical shape, a zeta-potential of -10.54 ± 1.37 mV, and 88.13 ± 0.01% entrapment efficiency. Nio-EEP can release EEP in a sustained manner and retains consistent physicochemical properties for a month. Nio-EEP has the capability to permeate the cellular membranes of C. neoformans, causing a significant decrease in the mRNA expression level of PLB1. Interestingly, biofilm formation, biofilm thickness, and the expression level of biofilm-related genes (UGD1 and UXS1) were also significantly reduced. Pre-treating with Nio-EEP prior to yeast infection reduced the intracellular replication of C. neoformans in alveolar macrophages by 47%. In conclusion, Nio-EEP mediates as an anti-virulence agent to inhibit PLB1 and biofilm production for preventing fungal colonization on lung epithelial cells and also decreases the intracellular replication of phagocytosed cryptococci. This nano-based EEP delivery might be a potential therapeutic strategy in the prophylaxis and treatment of pulmonary cryptococcosis in the future.
Assuntos
Antifúngicos , Biofilmes , Cryptococcus neoformans , Proteínas Fúngicas , Lisofosfolipase , Macrófagos Alveolares , Própole , Humanos , Biofilmes/efeitos dos fármacos , Linhagem Celular Tumoral , Criptococose/prevenção & controle , Criptococose/terapia , Cryptococcus neoformans/efeitos dos fármacos , Cryptococcus neoformans/enzimologia , Cryptococcus neoformans/patogenicidade , Etanol/química , Proteínas Fúngicas/antagonistas & inibidores , Lipossomos , Pneumopatias Fúngicas/prevenção & controle , Pneumopatias Fúngicas/terapia , Lisofosfolipase/antagonistas & inibidores , Macrófagos Alveolares/microbiologia , Própole/química , Própole/farmacologia , Virulência/efeitos dos fármacos , Fatores de Virulência/antagonistas & inibidores , Antifúngicos/química , Antifúngicos/farmacologiaRESUMO
We describe a 24-year-old man with type 1 diabetes mellitus and a cavitary lesion in the right upper lobe, caused by a zygomycete. Surgical resection plus liposomal amphotericin B therapy was successful. We discuss predisposing condition, clinical findings, diagnosis, and treatment of pulmonary zygomycosis.
Assuntos
Anfotericina B/administração & dosagem , Antifúngicos/administração & dosagem , Diabetes Mellitus/epidemiologia , Pneumopatias Fúngicas/epidemiologia , Pneumopatias Fúngicas/terapia , Zigomicose/epidemiologia , Zigomicose/terapia , Comorbidade , Humanos , Hospedeiro Imunocomprometido , Lipossomos , Pneumopatias Fúngicas/tratamento farmacológico , Pneumopatias Fúngicas/cirurgia , Masculino , Adulto Jovem , Zigomicose/tratamento farmacológico , Zigomicose/cirurgiaRESUMO
Pulmonary mucormycosis is a usually fatal opportunistic infection in immunocompromised patients. We describe the first case of an adult patient with hematological malignancy and profound neutropenia to survive a disseminated pulmonary Rhizomucor pusillus infection. Early diagnostic procedures combined with high doses of liposomal amphotericin B and surgical resection may have contributed to the successful outcome.