Exophiala is a genus comprising several species of opportunistic black yeasts,which belongs to Ascomycotina.It is a rare cause of fungal infections.However,infections are often chronic and recalcitrant,and while the n...Exophiala is a genus comprising several species of opportunistic black yeasts,which belongs to Ascomycotina.It is a rare cause of fungal infections.However,infections are often chronic and recalcitrant,and while the number of cases is steadily increasing in both immunocompromised and immunocompetent people,detailed knowledge remains scarce regarding infection mechanisms,virulence factors,specific predisposing factors,risk factors,and host response.The most common manifestations of Exophiala infection are skin infections,and the most frequent type of deep infection is pulmonary infection due to inhalation.The invasive disease ranges from cutaneous or subcutaneous infection to systemic dissemination to internal organs.The final identification of the causative organism should be achieved through a combination of several methods,including the newly introduced diagnostic analysis,matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry,together with sequencing of the ribosomal ribonucleic acid internal transcribed spacer region of the fungi,and histological and culture findings.Regarding treatment,because anti-infective agents and natural compounds exhibited poor antibiofilm activity,few treatments have ultimately been found to be effective for specific antifungal therapy,so the optimal antifungal therapy and duration of therapy for these infections remain unknown.Therefore,most forms of disease caused by Exophiala dermatitidis require aggressive combination therapies:Both surgical intervention and aggressive antifungal therapy with novel compounds and azoles are necessary for effective treatment.展开更多
Objective This study aimed to investigate the molecular mechanisms responsible for fluconazole resistance in clinical isolates of this pathogenic yeast.Methods A total of 41 Candida tropicalis strains were collected f...Objective This study aimed to investigate the molecular mechanisms responsible for fluconazole resistance in clinical isolates of this pathogenic yeast.Methods A total of 41 Candida tropicalis strains were collected from the clinical laboratory of Taiyuan City Central Hospital.Antifungal susceptibility testing was performed by ATB FUNGU 3 method.The 14 α-demethylase (ERG11) gene in all clinical isolates of Candida tropicalis were amplified by PCR,and their nucleotide sequences were determined in order to detect point mutations.Likewise,efflux transporters (CDR1 and MDR1) and ERG11 genes were tested by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) for their expression in Candida tropicalis cells at the mRNA level.Results The fluconazole-resistant rate of 41 Candida tropicalis was 12.2%.The amino acid substitutions in ERG11p of R245K,Y221F and V362I were found in fluconazole-resistant isolates.And no amino acid substitution was detected in fluconazole-susceptible ones.The mRNA level of CDR1,MDR1 and ERG11 genes in fluconazole-resistant isolates all showed overexpression compared with fluconazole-susceptible ones.Conclusions Missense mutations in ERG11 gene associated with overexpression of CDR1,MDR1 and ERG11 gene seemed to be responsible for the acquired fluconazole resistance of these clinical isolates.展开更多
文摘Exophiala is a genus comprising several species of opportunistic black yeasts,which belongs to Ascomycotina.It is a rare cause of fungal infections.However,infections are often chronic and recalcitrant,and while the number of cases is steadily increasing in both immunocompromised and immunocompetent people,detailed knowledge remains scarce regarding infection mechanisms,virulence factors,specific predisposing factors,risk factors,and host response.The most common manifestations of Exophiala infection are skin infections,and the most frequent type of deep infection is pulmonary infection due to inhalation.The invasive disease ranges from cutaneous or subcutaneous infection to systemic dissemination to internal organs.The final identification of the causative organism should be achieved through a combination of several methods,including the newly introduced diagnostic analysis,matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry,together with sequencing of the ribosomal ribonucleic acid internal transcribed spacer region of the fungi,and histological and culture findings.Regarding treatment,because anti-infective agents and natural compounds exhibited poor antibiofilm activity,few treatments have ultimately been found to be effective for specific antifungal therapy,so the optimal antifungal therapy and duration of therapy for these infections remain unknown.Therefore,most forms of disease caused by Exophiala dermatitidis require aggressive combination therapies:Both surgical intervention and aggressive antifungal therapy with novel compounds and azoles are necessary for effective treatment.
文摘Objective This study aimed to investigate the molecular mechanisms responsible for fluconazole resistance in clinical isolates of this pathogenic yeast.Methods A total of 41 Candida tropicalis strains were collected from the clinical laboratory of Taiyuan City Central Hospital.Antifungal susceptibility testing was performed by ATB FUNGU 3 method.The 14 α-demethylase (ERG11) gene in all clinical isolates of Candida tropicalis were amplified by PCR,and their nucleotide sequences were determined in order to detect point mutations.Likewise,efflux transporters (CDR1 and MDR1) and ERG11 genes were tested by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) for their expression in Candida tropicalis cells at the mRNA level.Results The fluconazole-resistant rate of 41 Candida tropicalis was 12.2%.The amino acid substitutions in ERG11p of R245K,Y221F and V362I were found in fluconazole-resistant isolates.And no amino acid substitution was detected in fluconazole-susceptible ones.The mRNA level of CDR1,MDR1 and ERG11 genes in fluconazole-resistant isolates all showed overexpression compared with fluconazole-susceptible ones.Conclusions Missense mutations in ERG11 gene associated with overexpression of CDR1,MDR1 and ERG11 gene seemed to be responsible for the acquired fluconazole resistance of these clinical isolates.
