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Impact of Morphological Sectors on Antifungal Susceptibility Testing and Virulence Studies.

ABSTRACT: Morphological heterogeneity of Aspergillus terreus cultures was observed during continued cultivation of amphotericin B (AMB)-resistant isolates on drug-free medium. Outgrowth leads to the emergence of multiple sectors that might result from increased growth rates at drug-free conditions. We evaluated the differences in AMB susceptibility and virulence between sector subcultures (ATSec), AMB-resistant (ATR) strains, and AMB-susceptible (ATS) strains. By comparing A. terreus AMB-resistant (ATR) strains and A. terreus sector (ATSec) cultures we observed a highly significant reduction of AMB MICs in ATSec (ATR MIC, 2 to 32 ?g/ml; ATSec MIC, 0.12 to 5 ?g/ml). Furthermore, Galleria mellonella survival studies revealed an enhanced virulence of ATSec, which was comparable with that of AMB-sensitive Aspergillus terreus strains (median survival rates for ATS isolates, 72 h; for ATSec isolate ATSec^G1, 84 h; for ATR isolates, 144 h). Our findings clearly demonstrate that spontaneous culture degeneration occurs in A. terreus and, most importantly, crucially impacts drug efficacy and virulence.

SUBMITTER: Jukic E

PROVIDER: S-EPMC5700351 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Impact of Morphological Sectors on Antifungal Susceptibility Testing and Virulence Studies.

Jukic Emina E Blatzer Michael M Binder Ulrike U Mayr Lisa L Lass-Flörl Cornelia C Lackner Michaela M

Antimicrobial agents and chemotherapy 20171122 12

Morphological heterogeneity of <i>Aspergillus terreus</i> cultures was observed during continued cultivation of amphotericin B (AMB)-resistant isolates on drug-free medium. Outgrowth leads to the emergence of multiple sectors that might result from increased growth rates at drug-free conditions. We evaluated the differences in AMB susceptibility and virulence between sector subcultures (ATSec), AMB-resistant (ATR) strains, and AMB-susceptible (ATS) strains. By comparing <i>A. terreus</i> AMB-res ...[more]

PMID: 28993330

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Project description:ObjectivesThe antifungal susceptibility testing (AFST) of yeast pathogen alerts clinicians about the potential emergence of resistance. In this study, we compared two commercial microdilution AFST methods: Sensititre YeastOne read visually (YO) and MICRONAUT-AM read visually (MN) or spectrophotometrically (MNV), interpreted with Clinical and Laboratory Standards Institute and European Committee on Antimicrobial Susceptibility Testing criteria, respectively.MethodsOverall, 97 strains from 19 yeast species were measured for nine antifungal drugs including a total of 873 observations. First, the minimal inhibitory concentration (MIC) was compared between YO and MNV, and between MNV and MN, either directly or by assigning them to five susceptibility categories. Those categories were based on the number of MIC dilutions around the breakpoint or epidemiological cut-off reference values (ECOFFs or ECVs). Second, YO and MNV methods were evaluated for their ability to detect the elevation of MICs due to mutation in antifungal resistance genes, thanks to pairs or triplets of isogenic strains isolated from a single patient along a treatment previously analyzed for antifungal resistance gene mutations. Reproducibility measurement was evaluated, thanks to three quality control (QC) strains.ResultsYO and MNV direct MIC comparisons obtained a global agreement of 67%. Performing susceptibility category comparisons, only 22% and 49% of the MICs could be assigned to categories using breakpoints and ECOFFs/ECVs, respectively, and 40% could not be assigned due to the lack of criteria in both consortia. The YO and MN susceptibility categories gave accuracies as low as 50%, revealing the difficulty to implement this method of comparison. In contrast, using the antifungal resistance gene sequences as a gold standard, we demonstrated that both methods (YO and MN) were equally able to detect the acquisition of resistance in the Candida strains, even if MN showed a global lower MIC elevation than YO. Finally, no major differences in reproducibility were observed between the three AFST methods.ConclusionThis study demonstrates the valuable use of both commercial microdilution AFST methods to detect antifungal resistance due to point mutations in antifungal resistance genes. We highlighted the difficulty to conduct conclusive analyses without antifungal gene sequence data as a gold standard. Indeed, MIC comparisons taking into account the consortia criteria of interpretation remain difficult even after the effort of harmonization.

Dataset Information

Impact of Morphological Sectors on Antifungal Susceptibility Testing and Virulence Studies.

Publications

Impact of Morphological Sectors on Antifungal Susceptibility Testing and Virulence Studies.

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