Peterson, M. | Search bioRxiv

bioRxiv2018

The fungal-specific Hda2 and Hda3 proteins regulate morphological switches in the human fungal pathogen Candida albicans.

The human fungal pathogen Candida albicans is responsible for millions of infections annually. Due to the few available anti-fungal drugs and the increasing incidence of drug resistance, the number of C. albicans infections is dramatically increasing. Morphological switches, such as the white-opaque switch and the yeast-hyphae switch, are key for the development of C. albicans pathogenic traits. Lysine deacetylases are emerging as important regulators of morphological switches. Yet, targeting lysine deacetylases for drug development is problematic due to the high homology between the fungal and human proteins that could result in toxicity. Here we provide evidence that the fungal specific proteins Hda2 and Hda3 interact with the lysine deacetylase Hda1. By combining phenotypic analyses with genome-wide transcriptome analyses, we demonstrate that Hda2 and Hda3 control C. albicans morphological switches. Under nutrient-rich conditions, deletion of HDA2 or HDA3 leads to moderate overexpression of the master regulator of white-opaque switching WOR1 and increase switching frequency. Under hyphae inducing conditions, deletion of HDA2 and HDA3 block hyphae development. However, deletion of HDA2 and HDA3 does not affect hyphae-formation and virulence in vivo. We propose that Hda2 and Hda3 are good targets for the development of anti-fungal drugs to be used in combination therapy.

microbiology↗

bioRxiv2017

The effect of chronic and acute stressors, and their interaction, on gonadal function: an experimental test during gonadal recrudescence

Organisms are expected to invest less in reproduction in response to a stressor, but theory predicts that this effect should depend on the frequency of stressors in the environment. Here we investigated how an acute stressor affected gonadal function in a songbird, and how long-term differences in the stress environment influenced these acute stress responses. We exposed male Dark-eyed Juncos (Junco hyemalis) either to chronic or minimal (control) disturbance during gonadal recrudescence, after which we measured baseline testosterone, testosterone after an acute handling stressor, and the ability to elevate testosterone in response to hormonal stimulation. In a 2x2 design, we then euthanized males from the two chronic treatment groups either immediately or after an acute stressor to investigate the effect of these treatments on the gonadal transcriptome. We found that chronically disturbed birds had marginally lower testosterone. The acute stressor suppressed testosterone in control birds, but not in the chronic disturbance group. The ability to elevate testosterone did not differ between the chronic treatments. Surprisingly, chronic disturbance had a weak effect on the testicular transcriptome, and did not affect transcriptomic response to the acute stressor. The acute stressor, on the other hand, upregulated cellular stress response, and affected expression of genes associated with hormonal stress-response. Overall, we show that both chronic and acute stressors affect reproductive function, and that chronic stress changes how acute stressors affect testosterone physiology. Our findings also suggest that acute and chronic stressors affect testes differently, and that gonadal function is relatively robust to long-term stressors.\n\nSummary statementAn acute stressor downregulated testosterone production, but this effect was absent in chronically disturbed birds. The acute stressor had a strong effect on the gonadal transcriptome, whereas chronic disturbance had a negligible effect.

physiology↗