The Dahms group currently studies microbial responses to external stimuli, including mechanisms associated with carbohydrate remodeling. We pioneered techniques to study the surface ultrastructure and physical properties associated with polarized and non-polarized growth in whole, live cells of moss (Physcomitrella patens) and fungi (Aspergillus nidulans) by atomic force microscopy (AFM). More recently we have been exploring invasion mechanisms for pathogenic (Escherichia coli, Pantoea stewartii, Neisseria gonorrhoeae) and symbiotic (Rhizobium leguminosarum) bacteria, and opportunistic fungal/yeast pathogens (A. nidulans, Candida albicans and krusei). We use a battery of microscopy techniques including AFM, fluorescence, laser scanning confocal (two-photon), transmission and scanning electron microscopy, to complement biochemical approaches. Of special interest to the group is how the microbial cell surface responds directly to external stimuli (calcium, copper, 2,4-D herbicide, antifungal agents) and how it is remodeled during growth, differentiation, and biofilm formation in wild type and genetically engineered microbes.
Candida is one of the most common opportunistic fungal pathogens in humans and its adhesion to the host cell is important for pathogenesis. While many studies have shown that there is an increased risk of developing Candida when an individual is immunosuppressed from cancer treatment, the inverse is also true: Candida can cause cancer. High throughput single-cell force spectroscopy and atomic force microscopy cantilevers functionalized with Candida were used to probe various epithelial cells, showing significantly greater adhesion between human cancer cells and Candida compared to non-cancerous cells. The increase in adhesion can be directly attributed to the altered cytoskeletal organization of the cancer cells. Ndlovu is currently collecting evidence for the role of Candida in cancer development through upregulation of oncogenes.
https://www.discoursemagazine.ca/clarifying-the-candida-cancer-connection/2021/05/10/
Several current and past members of the Dahms group have studied the antifungal mechanisms of plant-based essential oils and their components. Shahina examined C. albicans’ response to cinnamon bark oil and major component cinnamadehyde, rosemary oil, components 1,8-cineole, α-pinene with Sultana, the additive effect of clove and cinnamon leaf oils with Ndlovu and Molaeitabari, and the impact of three other common plant-based oil components: eugenol, citral, and carvacrol with Molaeitabari, Ndlovu and Acuna (BSc). C. albicans generates reactive oxygen species (ROS) at near-inhibitory essential oil concentrations, leading to cell membrane depolarization, vacuolar segregation, mitochondrial dysfunction, cell-cycle checkpoint deficiency, mitotic catastrophe, cell wall disruption and cell death, but interestingly at lower concentrations a ROS-independent response is accompanied by altered microtubular structure, reduced mycelial growth and biofilm inhibition. C. albicans resistance and susceptibility to essential oils are gene-dose dependent on Kar3 kinesin protein and its regulatory protein Cik1, and following essential oil exposure C. albicans tubulin and Kar3 proteins delocalize independent of ROS. Theoretical binding of 1,8-cineole, α-pinene, citral and eugenol adjacent to the cofactor binding sites of both αβ-tubulin and Kar3p support our experimentally observed mycelial and biofilm inhibition, a novel mechanism for microtubule defects.