1. Influence of poly-γ-glutamic acid on Candida drug resistance
Jakub Suchodolski, Yan Shauchuk, Marcin Łukaszewicz, Anna Krasowska
Department of Biotransformation, Faculty of Biotechnology, University of Wrocław, Poland
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γ- PGA is a biotechnological polymer of microbial origin
γ- PGA induces higher level of Mdr1p in C. albicans
PGA
low molecular weight
PGA
high molecular weight
Glucose
Poly-γ-glutamic acid (γ-PGA) is a biopolymer of glutamic acid, the component of the Japanese food Natto that is produced by Bacillus subtilis var. natto via soybean fermentation.
γ-PGA is a biodegradable and non-hazardous material of biological origin that has many potential biotechnological and biomedical applications.
γ-PGA nanoparticles containing amphotericin B were recently shown to have antifungal activity with reduced cytotoxicity -
Fluconazole +
Growth on γ-PGA induced Mdr1 expression in C. albicans, as shown by microscopic observations of a GFP-tagged pump. This was further confirmed by identifying a higher resistance to fluconazole using phenotypic tests of C. albicans Mdr1p single strain (with CDR deletions).
Natto - traditional Japanese food
Bacillus subtilis var. natto
Poly-γ-glutamic acid WT
cdr1∆
C. albicans - opportunistic fungal pathogen of humans
cdr2∆
Glucose
cdr1∆cdr2∆
cdr1∆cdr2∆mdr1∆
Candida albicans is a pathogenic yeast-like fungus that causes exogenous and endogenous infections. C. albicans strains exhibit multidrug resistance to commonly used antifungal agents, which correlates with overexpression of Cdr and Mdr efflux pumps that are located in the plasma membrane.
mdr1∆ WT
cdr1∆
PGA
low molecular weight
cdr2∆
cdr1∆cdr2∆
cdr1∆cdr2∆mdr1∆
mdr1∆
Intestin-407 cell line infected
by C. albicans WT
cdr1∆
PGA
high molecular weight
cdr2∆
cdr1∆cdr2∆
cdr1∆cdr2∆mdr1∆
Candida species assimilate γ-PGA as a carbon source
mdr1∆
PGA
high molecular weight
PGA
low molecular weight
Fluconazole concentration [µg/mL]
Glucose
C. albicans
Glucose mixed with γ-PGA induces fluconazole tolerance
C. parapsilosis
Growth on glucose mixed with γ-PGA (low molecular weight) induced fluconazole tolerance in C. albicans.
C. glabrata
C. krusei
The ability of four pathogenic Candida species (C. albicans, C. glabrata, C. krusei, and C. parapsilosis) to grow on γ-PGA (high or low molecular weight) as a sole carbon source was tested. The Candida species grew on both γ-PGAs, but at a lower rate than using glucose, especially C. glabrata.
This Project was supported by the Ministry of Science and Higher Eduction of the Republic of Poland, from the quality – promoting subsidy, under the Leading National Centre (KNOW) programme for the years 2014 – 2018.