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Differential Aspergillus lentulus echinocandin susceptibilities are Fksp independent.

ABSTRACT: The recently described species Aspergillus lentulus exhibits differential and reduced susceptibilities to echinocandins and other antifungal drugs in vitro. A. lentulus isolates overall are less susceptible to caspofungin, although they maintain susceptibility to anidulafungin and micafungin. Mutations or polymorphisms in fks, the gene encoding the catalytic subunit of ?-1,3-glucan synthase, are known to confer decreased susceptibility to echinocandins in Candida spp. and Aspergillus fumigatus. The analysis of the A. lentulus fks sequence did not reveal a polymorphism at any of the known hot-spot regions of the gene. Caspofungin and micafungin kinetic inhibition profiles of the A. lentulus glucan synthase were comparable to those from susceptible A. fumigatus enzymes. Although the basal cell wall chitin levels in A. lentulus averaged 60% of those in A. fumigatus, echinocandin treatment promoted the increase of cell wall chitin in both organisms, indicating that A. lentulus displays a compensatory chitin response similar to that of A. fumigatus. The data suggest that differential echinocandin susceptibilities in A. lentulus are independent of the echinocandin target, Fksp, and they emphasize the potential that the drugs' capacity to inhibit the target enzyme is unequal at the cellular level.

SUBMITTER: Staab JF

PROVIDER: S-EPMC2981225 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature

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Differential Aspergillus lentulus echinocandin susceptibilities are Fksp independent.

Staab Janet F JF Kahn Jennifer Nielsen JN Marr Kieren A KA

Antimicrobial agents and chemotherapy 20100920 12

The recently described species Aspergillus lentulus exhibits differential and reduced susceptibilities to echinocandins and other antifungal drugs in vitro. A. lentulus isolates overall are less susceptible to caspofungin, although they maintain susceptibility to anidulafungin and micafungin. Mutations or polymorphisms in fks, the gene encoding the catalytic subunit of β-1,3-glucan synthase, are known to confer decreased susceptibility to echinocandins in Candida spp. and Aspergillus fumigatus. ...[more]

PMID: 20855747

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Project description:BackgroundIn recent years, the number of invasive aspergillus infection cases caused by Aspergillus lentulus (A. lentulus) has gradually increased and this fungus is usually difficult to distinguish from Aspergillus fumigatus in morphology. All of these presents a great challenge to the treatment of invasive fungal infections caused by A. lentulus. The present study aims to discuss the antifungal resistance, virulence and inflammatory factors' changes after the infection of larvae of A. lentulus separated from patients with chronic obstructive pulmonary disease (COPD) to reflect the host immune response.MethodsA. lentulus isolated from COPD patients was identified by morphology and molecular biology, and its drug sensitivity was determined in vitro. Then the virulence factors and inflammatory response related factors of A. lentulus were determined by the model of A. lentulus infecting larvae. These were divided into three groups: A. lentulus standard strain, A. lentulus strain isolated from patients; PBS control. The infection model was formed by injecting the suspension of A. lentulus at a concentration of 1×106 CFU into larvae, in order to determine the (1,3)-?-D-glucan and galactomannan levels, and determine the caspase-1 and TNF-? concentration in Galleria mellonella larvae by RT-PCR.ResultsThe results revealed that A. lentulus had good sensitivity to itraconazole, voriconazole and micafungin, while (1,3)-?-D-glucan was negative in the two groups. The level of galactomannan in the two groups was higher than that in the control group, and the difference was statistically significant (P<0.05). However, there was no statistical difference between the standard strain group and patient strain group (P>0.05). After the infection of larvae, caspase-1 and TNF-? in the Galleria mellonella larvae increased in the two groups, and these elevated levels were statistically significant in both groups (P<0.05). However, there was no significant difference between the two groups (P>0.05).ConclusionsThere is no significant difference in virulence factor and host inflammatory response between A. lentulus isolated from COPD patients and standard strains. Galactomannan has more advantages in the early detection of A. lentulus invasive infection. Furthermore, the caspase-1-mediated inflammasome pathway may be involved in the host immune response to A. lentulus.

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Differential Aspergillus lentulus echinocandin susceptibilities are Fksp independent.

Publications

Differential Aspergillus lentulus echinocandin susceptibilities are Fksp independent.

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