Unmasking fungal pathogens by studying MAPK-dependent cell wall regulation in<i>Candida albicans</i>

Cullen, Paul J.; Edgerton, Mira

doi:10.1080/21505594.2016.1177695

Cited by 10 publications

(10 citation statements)

References 51 publications

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“…Recent studies suggested that Hst7 may lie between Cst20 and Cek1/Cek2 [37]. Moreover, CPH1 overexpression can induce the expression of CEK1, CEK2, and genes that are similar to the pheromones of Saccharomyces Cerevisiae, indicating that they may be regulated by the MAPK pathway [46][47][48][49]. Ace2, a transcription factor, has multiple functions in cell separation, hyphal morphogenesis, and biofilm formation and works with Efg1, Brg1, and Bcr1 to regulate transcription [50].…”

Section: Signaling Pathways Of Hyphal Morphogenesismentioning

confidence: 99%

The regulation of hyphae growth in Candida albicans

et al. 2020

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In the last decades, Candida albicans has served as the leading causal agent of life-threatening invasive infections with mortality rates approaching 40% despite treatment. Candida albicans (C. albicans) exists in three biological phases: yeast, pseudohyphae, and hyphae. Hyphae, which represent an important phase in the disease process, can cause tissue damage by invading mucosal epithelial cells then leading to blood infection. In this review, we summarized recent results from different fields of fungal cell biology that are instrumental in understanding hyphal growth. This includes research on the differences among C. albicans phases; the regulatory mechanism of hyphal growth, extension, and maintaining cutting-edge polarity; cross regulations of hyphal development and the virulence factors that cause serious infection. With a better understanding of the mechanism on mycelium formation, this review provides a theoretical basis for the identification of targets in candidiasis treatment. It also gives some reference to the study of antifungal drugs.

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Section: Signaling Pathways Of Hyphal Morphogenesismentioning

confidence: 99%

The regulation of hyphae growth in Candida albicans

et al. 2020

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“…Mediated by protein kinase C (Pkc1), this pathway is responsible for maintaining the integrity of the cell wall during growth, morphogenesis, and cell wall stress in C. albicans (Navarro-García et al, 1995 ; Lafayette et al, 2010 ). The cell wall is the first point of contact for antifungal drugs and represents an attractive therapeutic target in fungal pathogens (Cullen and Edgerton, 2016 ). As mentioned above, Hsp90 interacts with Mkc1, and Hsp90 and Hsp70 help to maintain phosphorylation of activated Pkc1 and control the degradation of fully primed and activated Pkc1 (Lum et al, 2013 ).…”

Section: Potential Antifungal Targets Within Hsps-associated Intracelmentioning

confidence: 99%

Candida albicans Heat Shock Proteins and Hsps-Associated Signaling Pathways as Potential Antifungal Targets

Gong

et al. 2017

Front. Cell. Infect. Microbiol.

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In recent decades, the incidence of invasive fungal infections has increased notably. Candida albicans (C. albicans), a common opportunistic fungal pathogen that dwells on human mucosal surfaces, can cause fungal infections, especially in immunocompromised and high-risk surgical patients. In addition, the wide use of antifungal agents has likely contributed to resistance of C. albicans to traditional antifungal drugs, increasing the difficulty of treatment. Thus, it is urgent to identify novel antifungal drugs to cope with C. albicans infections. Heat shock proteins (Hsps) exist in most organisms and are expressed in response to thermal stress. In C. albicans, Hsps control basic physiological activities or virulence via interaction with a variety of diverse regulators of cellular signaling pathways. Moreover, it has been demonstrated that Hsps confer drug resistance to C. albicans. Many studies have shown that disrupting the normal functions of C. albicans Hsps inhibits fungal growth or reverses the tolerance of C. albicans to traditional antifungal drugs. Here, we review known functions of the diverse Hsp family, Hsp-associated intracellular signaling pathways and potential antifungal targets based on these pathways in C. albicans. We hope this review will aid in revealing potential new roles of C. albicans Hsps in addition to canonical heat stress adaptions and provide more insight into identifying potential novel antifungal targets.

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“…The C . albicans cell wall is considered a good therapeutic drug target due to its role in fungal pathogenicity as it presents important virulence factors, antigenic cell wall proteins and polysaccharides, and serves as the intermediate for fungal-host interactions [3, 8, 9]. One potential method for improving anti-fungal strategies could be to enhance the detection of fungal cell wall antigens by host immune cells.…”

Section: Introductionmentioning

confidence: 99%

Exposure of Candida albicans β (1,3)-glucan is promoted by activation of the Cek1 pathway

et al. 2019

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Candida albicans is among the most common causes of human fungal infections and is an important source of mortality. C . albicans is able to diminish its detection by innate immune cells through masking of β (1,3)-glucan in the inner cell wall with an outer layer of heavily glycosylated mannoproteins (mannan). However, mutations or drugs that disrupt the cell wall can lead to exposure of β (1,3)-glucan (unmasking) and enhanced detection by innate immune cells through receptors like Dectin-1, the C-type signaling lectin. Previously, our lab showed that the pathway for synthesizing the phospholipid phosphatidylserine (PS) plays a role in β (1,3)-glucan masking. The homozygous PS synthase knockout mutant, cho1Δ/Δ , exhibits increased exposure of β (1,3)-glucan. Several Mitogen Activated Protein Kinase (MAPK) pathways and their upstream Rho-type small GTPases are important for regulating cell wall biogenesis and remodeling. In the cho1Δ/Δ mutant, both the Cek1 and Mkc1 MAPKs are constitutively activated, and they act downstream of the small GTPases Cdc42 and Rho1, respectively. In addition, Cdc42 activity is up-regulated in cho1Δ/Δ . Thus, it was hypothesized that activation of Cdc42 or Rho1 and their downstream kinases cause unmasking. Disruption of MKC1 does not decrease unmasking in cho1Δ/Δ , and hyperactivation of Rho1 in wild-type cells increases unmasking and activation of both Cek1 and Mkc1. Moreover, independent hyperactivation of the MAP kinase kinase kinase Ste11 in wild-type cells leads to Cek1 activation and increased β (1,3)-glucan exposure. Thus, upregulation of the Cek1 MAPK pathway causes unmasking, and may be responsible for unmasking in cho1Δ/Δ .

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Unmasking fungal pathogens by studying MAPK-dependent cell wall regulation inCandida albicans

Cited by 10 publications

References 51 publications

The regulation of hyphae growth in Candida albicans

The regulation of hyphae growth in Candida albicans

Candida albicans Heat Shock Proteins and Hsps-Associated Signaling Pathways as Potential Antifungal Targets

Exposure of Candida albicans β (1,3)-glucan is promoted by activation of the Cek1 pathway

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