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Kalinina, I.

Publications and source records attributed to Kalinina, I..

3 recordsLinked to original sources

The Cryptococcus neoformans titanide is a pathogenic morphotype that arises from typical yeast cells in response to host-relevant conditions

Fungal morphogenesis is a major driver of disease outcome. For the opportunistic fungal pathogen Cryptococcus neoformans, extreme morphological heterogeneity within the lung environment drives dissemination, immune evasion, and drug resistance. One such morphotype is the small, oval, titanide (2-3 {micro}m). This poorly understood cell type is prevalent in lung histology and under in vitro conditions that mimic the host environment to generate cellular heterogeneity. Titanides appear after 24 hours post-induction and by 72 hours are the dominant morphotype. Despite their prevalence and the significance of cryptococcal morphogenesis for virulence, their origin remains unclear and their biology unstudied. Using TEM and fluorescence microscopy we demonstrate that titanides display distinct morphological features; they possess thin cell walls and capsules with reduced Pathogen Associated Molecular Pattern exposure and altered distribution. These features distinguish titanides from previously described C. neoformans small cells such as in vivo seed cells (4-6 {micro}m, high cell-wall mannan content) and micro cells (round, <1 m, with thick cell walls). Using microfluidics, we answer key questions pertaining to their origin and cell fate and further our understanding of C. neoformans typical cell and titanide morphological plasticity in host-relevant conditions. Interestingly, despite their thin cell walls, we show that titanides display an increased resistance to cell wall/membrane stressors and are an effective infectious propagule in a murine model. Together, these findings establish a definition and essential characterisation of the titanide morphotype and provide new insight into a key player in C. neoformans pathogenesis.

microbiology↗

Copper Driven Mutualism of Candida albicans and Staphylococcus aureus Interkingdom Biofilms

Although fungi and bacteria commonly coexist within polymicrobial communities, the molecular mechanisms underlying their interactions are still not well understood. Here, we show that the fungus Candida albicans forms biofilms with the bacterium Staphylococcus aureus along a nutritional axis of mutualism and propose that "a copper economy" shapes fungal-bacterial biofilm interactions. Using in vitro biofilms formed on plastic, we found that dual species biofilms are consistently larger than single-species counterparts, indicating a cooperative interaction. Dual species proteomic analysis revealed non-reciprocal copper handling: C. albicans increased copper uptake via transporter Ctr1, while S. aureus enhanced copper export via regulator CsoR and export chaperone CopZ. Dual species biofilms exhibited specific sensitivity to both copper depletion and supplementation, with corresponding reductions in biomass. We identified fungal copper import as the crucial element in mutualistic interactions between C. albicans and staphylococcal species. Moreover, fungal hyphae served as a critical scaffold for biofilm architecture, a role that was compromised under copper-replete conditions. Notably, copper nanoparticles disrupted these dual species biofilms, highlighting a potential therapeutic avenue. Furthermore, we extend the role of C. albicans copper import to mutualistic interactions with additional bacterial species. Our findings establish copper as a central mediator of C. albicans and S. aureus cooperation and suggest that a "copper economy" underpins mutualistic interactions in biofilms.

microbiology↗

Cytoskeleton mechanics determine resting size and activation dynamics of platelets.

Platelets are cell fragments of various size that help maintain hemostasis. The way platelets respond during a clotting process is known to depend on their size, with important physiological consequences. We characterized the cytoskeleton of platelets as a function of their size. In resting Human and Mice platelets, we find a quadradic law between the size of a platelet and the amount of microtubule polymer it contains. We further estimate the length and number of microtubules in the marginal band using Electron and Super-resolution microscopy. In platelets activated with ADP, the marginal band coils as a consequence of cortical contraction driven by actin. We observe that this elastic coiling response is accompanied by a reversible shortening of the marginal band. Moreover, larger platelets have a higher propensity to coil. These results establish the dynamic equilibrium that is responsible for platelet size and differential response on a more quantitative level.\n\nHighlightsO_LIPlatelet size scales consistently with amount of polymerized tubulin in both mouse and human.\nC_LIO_LIPolymerized actin is required for ADP-induced marginal band coiling.\nC_LIO_LIUpon activation, the marginal band exhibits a reversible visco-elastic response involving shortening.\nC_LIO_LILarger marginal bands have a higher propensity to coil than shorter ones.\nC_LI\n\nIn briefThe cytoskeleton is adapted to platelet size and its mechanical properties determine propensity of a platelet to undergo morphological changes in response to agonists.

cell biology↗