Mild Heat Stress Affects on the Cell Wall Structure in <i>Candida albicans</i> Biofilm

Abstract

We previously reported that Candida albicans responded to mild heat stress in a range of temperature elevations simulating fever, and concluded that mild heat stress increases susceptibility to antifungal drugs. In this study, we show that mild heat stress causes a morphological change in hyphae during the process of biofilm formation. We found that mild heat stress extended the period of hyphal stage maintenance in C. albicans biofilm. Although the rate of hyphal change from yeast form to hyphal form reached the maximum within 3 hr, later, almost every cell quickly reverted to the yeast growth phase within 6 hr at 37ºC but not at 39ºC, or under mild heat stress. Electron microscopy using a smart specimen preparation technique revealed that mild heat stress significantly increased the thickness of the inner cell wall accompanied by a decrease in density of the outer cell wall in the hyphae of C. albicans biofilm. To identify the gene responsible for the morphological changes associated with mild heat stress, we performed microarray gene expression analysis. Eleven genes were upregulated and 17 genes were downregulated under mild heat stress in biofilm cells. The increased PHR1 gene expression in response to mild heat stress was confirmed in quantitative RT-PCR analysis. The mutant upregulated PHR1 expression showed the same sensitivity against antifungal drug micafungin as dependent on mild heat stress. Our findings point to possible therapeutic effects of hyperthermia as well as to the effect of fever during infections.

The Heat Shock Transcription Factor HsfA Is Essential for Thermotolerance and Regulates Cell Wall Integrity in Aspergillus fumigatus

“…These results suggest that the cell wall expansion is necessary to sustain thermoadaptation without loss of viability. Increased cell wall thickness has also been recently reported in C. albicans biofilm hyphae during mild heat stress (Ikezaki et al, 2019). However, our results reveal that such modifications in cell wall architecture are very rapidly sensed by the cells since we detect a thickening of this structure as early as after 5 min of HS exposure (Figure 1).…”

How does temperature trigger biofilm adhesion and growth in Candida albicans and two non‐Candida albicans Candida species?

“…A recent paper has evaluated the difference induced in the biofilm transcriptome at 37 and 39°C of C. albicans strain, finding that 17 genes were downregulated and 11 upregulated at a significant level. 48 Among the genes involved in cell wall metabolism, MNN22, which is repressed in core stress response, was one of the most In conclusion, the Candida sessile cells react to the temperature with different strain-dependent responses that are probably instrumental to guarantee the best success to cells for the infection, attachment and growth to occur. These observations reinforce the concept of temperature as a major trigger in the evolution of these species.…”

“…A recent paper has evaluated the difference induced in the biofilm transcriptome at 37 and 39°C of C. albicans strain, finding that 17 genes were downregulated and 11 upregulated at a significant level 48 . Among the genes involved in cell wall metabolism, MNN22, which is repressed in core stress response, was one of the most downregulated genes at 39°C, indicating that this 2°C difference induces an active stress response.…”

“… 47 To date, the literature about the effect of temperature on biofilm formation of Candida species is scarce with few studies carried out on the solely C. albicans . 30 , 48 Therefore, scarce knowledge is available on the ability of C. albicans and NCAC species to survive and form biofilm when exposed to the high temperatures implemented by the human body as a natural defence against the infection.…”

“…Both the resistance to high temperatures and the ability to form biofilm are threatening factors of these yeast species, the combination of which could have really dangerous outcomes on the epidemiology of these fungi, especially considering the general increase in average temperatures observed in recent years 47 . To date, the literature about the effect of temperature on biofilm formation of Candida species is scarce with few studies carried out on the solely C. albicans 30,48 . Therefore, scarce knowledge is available on the ability of C. albicans and NCAC species to survive and form biofilm when exposed to the high temperatures implemented by the human body as a natural defence against the infection.…”