Contact-induced apical asymmetry drives the thigmotropic responses ofCandida albicanshyphae

Abstract

Filamentous hyphae of the human pathogen, Candida albicans, invade mucosal layers and medical silicones. In vitro, hyphal tips reorient thigmotropically on contact with small obstacles. It is not known how surface topography is sensed but hyphae lacking the cortical marker, Rsr1/Bud1, are unresponsive. We show that, on surfaces, the morphology of hyphal tips and the position of internal polarity protein complexes are asymmetrically skewed towards the substratum and biased towards the softer of two surfaces. In nano-fabricated chambers, the Spitzenkörper (Spk) responded to touch by translocating across the apex towards the point of contact, where its stable maintenance correlated with contour-following growth. In the rsr1Δ mutant, the position of the Spk meandered and these responses were attenuated. Perpendicular collision caused lateral Spk oscillation within the tip until after establishment of a new growth axis, suggesting Spk position does not predict the direction of growth in C. albicans. Acute tip reorientation occurred only in cells where forward growth was countered by hyphal friction sufficient to generate a tip force of ∼ 8.7 μN (1.2 MPa), more than that required to penetrate host cell membranes. These findings suggest mechanisms through which the organization of hyphal tip growth in C. albicans facilitates the probing, penetration and invasion of host tissue.

A Positive Feedback between Growth and Polarity Provides Directional Persistency and Flexibility to the Process of Tip Growth

“…Single-Cell Manipulation of Growth Rate Impacts the Stability of GTP-Cdc42 Polarity Polar domains of the active form of the Rho-like GTPase Cdc42 promote local growth. Studies in yeast and fungal cells have shown that polar domains can oftentimes become unstable, assembling and disassembling at successive positions around the cell surface [5,7,9,[11][12][13]. Motivated by the observation that faint and unstable domains are associated with slow surface growth [7,9,12], we sought to dissect the causal-effect relationships between growth and polarity, and assay in a systematic manner the impact of modulating surface growth rate on polarity stability.…”

Candida albicans cell-type switching and functional plasticity in the mammalian host

“…Traditionally, the filamentous forms (hyphae and pseudohyphae) were considered pathogenic, whereas yeasts were primarily viewed as commensals. Hyphae are intrinsically invasive on solid media and hyphal tip cells exhibit thigmotropism, or the unusual ability to ‘track’ along substrate surface irregularities 31 (reviewed in 32 ). Moreover, hyphae express numerous cell type-specific virulence factors such as adhesins (for example, Hwp1, Als3, Als10, Fav2 and Pga55), tissue-degrading enzymes (for example, Sap4, Sap5 and Sap6), antioxidant defense proteins (for example, Sod5), and even a recently described cytolytic peptide toxin (Ece1).…”

Neutrophil Interactions Stimulate Evasive Hyphal Branching by Aspergillus fumigatus

“…fumigatus [27], while others have used microfluidic techniques to identify immunosuppressive fungal metabolites [28]. For microbiologists, microfluidics has provided a useful platform for imaging active Candida hyphal growth at high resolution, revealing that internal polarity protein complexes are asymmetrically skewed toward softer substratum [29]. …”