Host carbon sources modulate cell wall architecture, drug resistance and virulence in a fungal pathogen.

Iuliana V Ene,Neil A R Gow,Ashok K Adya,Alexandra C Brand,Donna M Maccallum,Silvia Wehmeier,Alistair J P Brown

doi:10.1111/j.1462-5822.2012.01813.x

Iuliana V Ene, Neil A R Gow + Show 5 more

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https://doi.org/10.1111/j.1462-5822.2012.01813.x

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Abstract

The survival of all microbes depends upon their ability to respond to environmental challenges. To establish infection, pathogens such as Candida albicans must mount effective stress responses to counter host defences while adapting to dynamic changes in nutrient status within host niches. Studies of C. albicans stress adaptation have generally been performed on glucose-grown cells, leaving the effects of alternative carbon sources upon stress resistance largely unexplored. We have shown that growth on alternative carbon sources, such as lactate, strongly influence the resistance of C. albicans to antifungal drugs, osmotic and cell wall stresses. Similar trends were observed in clinical isolates and other pathogenic Candida species. The increased stress resistance of C. albicans was not dependent on key stress (Hog1) and cell integrity (Mkc1) signalling pathways. Instead, increased stress resistance was promoted by major changes in the architecture and biophysical properties of the cell wall. Glucose- and lactate-grown cells displayed significant differences in cell wall mass, ultrastructure, elasticity and adhesion. Changes in carbon source also altered the virulence of C. albicans in models of systemic candidiasis and vaginitis, confirming the importance of alternative carbon sources within host niches during C. albicans infections.

Highlights

Most microbes inhabit microenvironments that are in a constant state of flux
Studies of C. albicans stress adaptation have generally been performed on glucose-grown cells, leaving the effects of alternative carbon sources upon stress resistance largely unexplored
We have shown that growth on alternative carbon sources, such as lactate, strongly influence the resistance of C. albicans to antifungal drugs, osmotic and cell wall stresses

Summary

Introduction

Most microbes inhabit microenvironments that are in a constant state of flux. This is true for clinically important microbial pathogens which must counter the biochemical and immunological insults imposed by their host. Candida albicans is a major fungal pathogen of humans that can cause a variety of infections (Calderone and Clancy, 2011). In severely immunocompromised patients C. albicans can thrive in the bloodstream, colonizing and forming lesions on internal organs (Perlroth et al, 2007; Pfaller and Diekema, 2010). Up to half of these systemic infections are fatal (Perlroth et al, 2007). C. albicans can thrive within diverse niches in its human host

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