# AFM-IR Insights Into Cell Wall Remodeling and Protein Reorganization in Candida auris Versus Candida albicans

## TL;DR

This study uses advanced imaging to compare the cell structures of two fungi, revealing why one is more drug-resistant and dangerous.

## Contribution

A multiscale spectroscopic platform is introduced to analyze fungal cell structures, revealing unique features of Candida auris.

## Key findings

- Candida auris has a more robust and heterogeneous polysaccharide network compared to Candida albicans.
- C. auris shows higher lipid levels with longer chains and distinct protein structures at the nanoscale.
- Ethanol fixation preserves cell morphology and improves nanoscale spectroscopic analysis reliability.

## Abstract

Candida auris is an emerging
multidrug-resistant
pathogen that poses a serious threat to public health, while Candida albicans is a well-studied commensal yeast.
Investigating the structural and biochemical basis of C. auris persistence and drug resistance requires
approaches capable of resolving both global and local cellular features.
Here, we applied Fourier-transform infrared spectroscopy in combination
with atomic force microscopy-infrared spectroscopy measurements to
examine fungal cells at multiple scales, from colony-level biochemical
composition to nanoscale organization within single cells. Ethanol
fixation was implemented to safely handle C. auris, and its effects were first assessed in C. albicans. While fixation induced measurable modifications in lipids, glucans,
and protein secondary structures, cell morphology was maintained,
and dehydration improved AFM-IR reproducibility by reducing topographical
artifacts. This validation confirmed that fixed cells can serve as
reliable models for nanoscale spectroscopic analysis of pathogenic
fungi. Comparison of fixed C. albicans and C. auris revealed striking species-specific
differences. C. auris exhibited a more
robust and heterogeneous polysaccharide network, including enriched
mannan and β-1,3-glucan content, higher lipid levels with longer
chains, and distinctive protein secondary structure features at the
nanoscale, such as increased antiparallel β-sheets. These structural
characteristics likely contribute to its environmental resilience,
virulence, and multidrug resistance. Overall, this study introduces
a multiscale spectroscopic platform that captures both global and
nanoscale biochemical features of fungal cells, providing unique insights
into C. auris biology and offering
a foundation for future studies on antifungal responses and pathogen
diagnostics.