Biology subjects

Bachellier-Bassi, S.

Publications and source records attributed to Bachellier-Bassi, S..

6 recordsLinked to original sources

bioRxiv2025

Snooping helices: The elastic path finding algorithm of growing hyphae

How living organisms utilize physical mechanisms to sense their environments and make informed decisions is an open question at the interface of biology and physics. In filamentous organisms like fungal hyphae, the decisions are taken by their growing tip cells and later imprinted onto the rest of the multi-cellular filament. Here we report on the growth and pathfinding of hyphae from the opportunistic fungal pathogen Candida albicans, whose ability to cross intestinal epithelial layers is associated to severe systemic infections in humans. It has been sporadically reported that C. albicanss hyphae display helical growth inside or on top of agar gels, helicity turning in the latter case into two-dimensional oscillatory shapes. We provide an extended description of oscillatory C. albicans hyphal growth modalities, revealed under various physical confinements thanks to the use of dedicated microfluidic devices and quantitative time-lapse imaging-based analysis. These include sudden sliding events accompanied by curvature switching of the tip portion, resulting in a final oscillatory morphology of the entire filament, and stable curved tips moving against vertical microfluidic channels walls. These behaviors are unified under the formalism of growing squeezed helices, in which the final hyphal curved shapes result from an elastic energy minimization of a spatially confined helical portion at the tip followed by a continuous solidification front. Ultimately, the combination of our experimental results and theoretical framework provide an insight into the penetration strategy of C. albicans hyphae, which is essential for the virulence of this fungal microorganism. Significance StatementProprioception is the integrated sense of self-movement and body position in complex organisms. Here we describe a novel, mechanical form of proprioception driving directional choice making in tip-growing helical organisms. We show that C. albicans hyphae utilize their built-in helicity as an environment-scanning mechanism to explore their surrounding and find target surfaces for invasion. When confined to surfaces, hyphae continue producing in-plane oscillatory shapes that promote further invasive behavior. C. albicans inherent mechanical instabilities regulate the switching of growth direction and their abrupt directional decisions can be understood as elastic bifurcations of squeezed, confined helices.

biophysics↗

bioRxiv2024

Beta-1,6-glucan plays a central role in the structure and remodeling of the bilaminate fungal cell wall

The cell wall of human fungal pathogens plays critical roles as an architectural scaffold and as a target and modulator of the host immune response. Although the cell wall of the pathogenic yeast Candida albicans is intensively studied, one of the major fibrillar components in its cell wall, {beta}-1,6- glucan, has been largely neglected. Here, we show that {beta}-1,6-glucan is essential for bilayered cell wall organization, cell wall integrity and filamentous growth. For the first time, we show that {beta}-1,6- glucan production compensates the defect in mannan elongation in the outer layer of the cell wall. In addition, {beta}-1,6-glucan dynamics are also coordinated by host environmental stimuli and stresses with wall remodeling, where the regulation of {beta}-1,6-glucan structure and chain length is a crucial process. As we point out that {beta}-1,6-glucan is exposed at the yeast surface and modulate immune response, {beta}-1,6-glucan must be considered a key factor in host-pathogen interactions.

microbiology↗

bioRxiv2023

Metabolic reprogramming during Candida albicans planktonic-biofilm transition is modulated by the ZCF15 and ZCF26 paralogs

Candida albicans is a commensal of the human microbiota that can form biofilms on implanted medical devices. These biofilms are tolerant to antifungals and to the host immune system. To identify novel genes modulating C. albicans biofilm formation, we performed a large-scale screen with 2454 C. albicans doxycycline-dependent overexpression strains and identified 16 genes whose overexpression significantly hampered biofilm formation. Among those, overexpression of the ZCF15 and ZCF26 paralogs that encode transcription factors and have orthologs only in biofilm-forming species of the Candida clade, caused impaired biofilm formation both in vitro and in vivo. Interestingly, overexpression of ZCF15 specifically impeded biofilm formation without any defect in hyphal growth. Transcript profiling, transcription factor binding, and phenotypic microarray analyses conducted upon overexpression of ZCF15 and ZCF26 demonstrated their direct role in reprogramming cellular metabolism by regulating glycolytic cycle and tricarboxylic acid cycle genes. Taken together, this study has identified a new set of biofilm regulators, including ZCF15 and ZCF26, that appear to control biofilm development through their specific role in metabolic remodeling.

microbiology↗

bioRxiv2022

Bending stiffness of Candida albicans hyphae reflects adaptive behavior of the fungal cell wall

The cell wall is a key component of fungi. It constitutes a stiff shell which counteracts internal cell turgor pressure. Its mechanical properties thus contribute to define cell morphology. Measurements of the elastic moduli of the fungal cell wall have been carried out in many species including Candida albicans, a major human opportunistic pathogen. They mainly relied on atomic force microscopy, and mostly considered the yeast form. We developed a parallelized pressure-actuated microfluidic device to measure the bending stiffness of hyphae. We found that the cell wall stiffness lies in the MPa range. We the used three different ways to disrupt cell wall physiology: inhibition of beta-glucan synthesis, a key component of the inner cell wall; application of an hyperosmotic shock triggering a sudden decrease of the hyphal diameter; deletion of two genes encoding GPI-modified cell wall proteins resulting in reduced cell wall thickness. The bending stiffness values were affected to different extents by these environmental stresses or genetic modifications. Overall, our results support the elastic nature of the cell wall and its ability to remodel at the scale of the entire hypha over minutes.

biophysics↗

bioRxiv2018

Candida albicans biofilms are generally devoid of persister cells

Candida albicans is known for its ability to form biofilms - communities of microorganisms embedded in an extracellular matrix developing on different surfaces. Biofilms are highly tolerant to antifungal therapy. This phenomenon has been partially explained by the appearance of so-called persister cells, phenotypic variants of wild-type cells, capable of surviving very high concentrations of antimicrobial agents. Persister cells in C. albicans were found exceptionally in biofilms while none were detected in planktonic cultures of this fungus. Yet, this topic remains controversial as others could not observe persister cells in biofilms formed by the C. albicans SC5314 laboratory strain. Due to ambiguous data in the literature, this work aimed to reevaluate the presence of persister cells in C. albicans biofilms. We demonstrated that isolation of C. albicans \"persister cells\" as described previously was likely to be the result of survival of biofilm cells that were not reached by the antifungal. We tested biofilms of SC5314 and its derivatives, as well as 95 clinical isolates, using an improved protocol, demonstrating that persister cells are not a characteristic trait of C. albicans biofilms. Although some clinical isolates are able to yield survivors upon the antifungal treatment of biofilms, this phenomenon is rather stochastic and inconsistent.

microbiology↗

bioRxiv2018

Generating genomic platforms to study Candida albicans pathogenesis

The advent of the genomic era has made elucidating gene function at large scale a pressing challenge. ORFeome collections, whereby almost all ORFs of a given species are cloned and can be subsequently leveraged in multiple functional genomic approaches, represent valuable resources towards this endeavor. Here we provide novel, genome-scale tools for the study of Candida albicans, a commensal yeast that is also responsible for frequent superficial and disseminated infections in humans. We have generated an ORFeome collection composed of 5,102 ORFs cloned in a Gateway donor vector, representing 83% of the currently annotated coding sequences of C. albicans. Sequencing data of the cloned ORFs are available in the CandidaOrfDB database at http://candidaorfeome.eu. We also engineered 49 expression vectors with a choice of promoters, tags, and selection markers and demonstrated their applicability to the study of target ORFs transferred from the C. albicans ORFeome. In addition, the use of the ORFeome in the detection of protein-protein interaction was demonstrated. Mating-compatible strains as well as Gateway-compatible two-hybrid vectors were engineered, validated and used in a proof of concept experiment. These unique and valuable resources should greatly facilitate future functional studies in C. albicans and the elucidation of mechanisms that underlie its pathogenicity.

genomics↗