Chemometric analysis of the multidrug resistance in strains of Penicillium digitatum1

¹Presented at CMTPI 2007: Computational Methods in Toxicology and Pharmacology Integrating Internet Resources (Moscow, Russia, September 1–5, 2007).

Abstract

Multidrug resistance activities pECr₅₀ of diverse strains of pathogenic fungus Penicillium digitatum against seven toxicants were studied by Principal Component Analysis (PCA) and Hierarchical Cluster Analysis (HCA). Fungal growth data (radii, circumferences, surface areas of fungal colonies, radius differences and ratios) in absence and presence of toxicants were used to derive eight new descriptors for 35 fungal strains. This data set was studied by PCA and HCA, and was correlated with the genome descriptor PCR for expression of gene CYP51 by Partial Least Squares (PLS) regression. Both analyses of pECr₅₀ data and of fungal growth data have identified baseline resistance character, origin and target fruits of the fungal strains. In addition, the analysis of fungal growth data shows that fungal growth morphology is multivariate by nature, meaning that experimental data can be explored more intensely than in usual practice. Fungal growth is directly related to the production of enzyme P450_14DM as the main resistance mechanism of P. digitatum against demethylation inhibitors. This is visible from a parsimonious PLS model (two principal components, Q ² = 0.985, R ² = 0.991, SEV = 0.028), validated with eight strains in the external validation set (Q ² _ev = 0.982, R ² _ev = 0.990, SEC_ev = 0.025). Chemometric methods in exploring bioassay data are promising approaches to obtain useful information on fungal resistance and to apply these findings in practice.

¹Presented at CMTPI 2007: Computational Methods in Toxicology and Pharmacology Integrating Internet Resources (Moscow, Russia, September 1–5, 2007).

Keywords:

• chemometrics
• demethylation inhibitors
• multidrug resistance
• exploratory analysis
• partial least squares
• green mould

Acknowledgements

The authors acknowledge The State of São Paulo Funding Agency FAPESP for financial support.

Notes

¹Presented at CMTPI 2007: Computational Methods in Toxicology and Pharmacology Integrating Internet Resources (Moscow, Russia, September 1–5, 2007).