Atomic force microscopy and spectroscopy: A versatile toolbox to decipher Candida albicans pathogenicity

Candida albicans is one of the most medically important pathogens, mainly due to its high frequency and strong ability to form biofilm causing severe human infections. Therefore, a current challenge in public health remains to further elucidate C. albicans virulence factors to help developing new targeted therapeutic strategies. Understanding pathogenicity at the molecular level is still at its infancy due to the lack of high-resolution techniques capable of imaging, localizing and probing the biophysical properties of fungal cell wall components in relation to their function. This review discusses how atomic force microscopy (AFM) and its multifunctional applications have recently helped to clarify the surface composition and the mechanisms involved in the adhesion and invasion of C. albicans. Based on recent breakthroughs, we describe how single molecule detection of adhesins (Als proteins) helps understanding their regulation and changes of mechanical properties upon morphogenesis and drug treatment. We also point out the role played by cell wall glycans in the adhesion. Lastly, we demonstrate how AFM imaging can reveal fine nanostructures of the main steps of C. albicans-macrophage interaction. We believe this overview-and the newly developed methodologies that we discuss-demonstrates the contribution of AFM in elucidating fungal pathogenicity.