Candida albicans CHK1 gene from two-component system is essential for its pathogenicity in oral candidiasis

Zhou, Yujie; Cheng, Lei; Liao, Binyou; Shi, Yangyang; Niu, Yulong; Zhu, Chengguang; Ye, Xingchen; Zhou, Xuedong; Ren, Biao

doi:10.1007/s00253-021-11187-0

Cited by 14 publications

(13 citation statements)

References 71 publications

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“…As a unique protein found in a few fungal species, C. albicans ’ Chkp1 has been confirmed to be significant to many biological processes and pathogenic traits, including the regulation of cell wall glucan and mannan biosynthesis ( Li et al, 2009 ), controlling population sensing (quorum sensing) ( Kruppa et al, 2004 ), and mediating osmotic and oxidant stress responses ( Li et al, 2004 ). The deletion of CHK1 reduces virulence in a murine disseminated model ( Calera et al, 1999b ) and in a mucosal model ( Zhou et al, 2021 ), and has been explained as an effect of decreased expression of fungal virulence factors, including ALS2, SAP6, and YWP1 ( Zhou et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Deletion of Non-histidine Domains of Histidine Kinase CHK1 Diminishes the Infectivity of Candida albicans in an Oral Mucosal Model

Feng

Bian²,

Pang³

et al. 2022

Front. Microbiol.

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ObjectivesThe histidine kinase (HK) CHK1 and other protein kinases in Candida albicans are key players in the development of hyphae. This study is designed to determine the functional roles of the S_Tkc domain (protein kinase) and the GAF domain of C. albicans CHK1 in hyphal formation and mucosal invasion.MethodsThe domain mutants CHK25 (ΔS_TkcCHK1/Δchk1) and CHK26 (ΔS_TkcΔgafCHK1/Δchk1) were first constructed by the his1-URA3-his1 method and confirmed by sequencing and Southern blots. A mouse tongue infection model was used to evaluate the hyphal invasion and fungal loads in each domain mutant, full-gene deletion mutant CHK21 (chk1Δ/chk1Δ), re-constituted strain CHK23 (chk1Δ/CHK1), and wild type (WT) from day 1 to day 5. The degree of invasion and damage to the oral mucosa of mice in each strain-infected group was evaluated in vivo and compared with germ tube rate and hyphal formation in vitro.ResultWhen compared with severe mucosal damage and massive hyphal formation in WT- or CHK23-infected mouse tongues, the deletion of S_Tkc domain (CHK25) caused mild mucosal damage, and fungal invasion was eliminated as we observed in full-gene mutant CHK21. However, the deletion of S_Tkc and GAF (CHK26) partially restored the hyphal invasion and mucosal tissue damage that were exhibited in WT and CHK23. Regardless of the in vivo results, the decreased hyphal formation and germ tube in vitro were less apparent and quite similar between CHK25 and CHK26, especially at the late stage of the log phase where CHK26 was closer to WT and CHK23. However, growth defect and hyphal impairment of both domain mutants were similar to CHK21 in the early stages.ConclusionOur data suggest that both protein kinase (S_Tkc) and GAF domains in C. albicans CHK1 are required for hyphal invasiveness in mucosal tissue. The appropriate initiation of cell growth and hyphal formation at the lag phase is likely mediated by these two functional domains of CHK1 to maintain in vivo infectivity of C. albicans.

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Section: Discussionmentioning

confidence: 99%

Deletion of Non-histidine Domains of Histidine Kinase CHK1 Diminishes the Infectivity of Candida albicans in an Oral Mucosal Model

Feng

Bian²,

Pang³

et al. 2022

Front. Microbiol.

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“…Candida albicans is a major opportunistic fungal pathogen in oral cavity and highly associated with several oral diseases, such as caries (especially root caries; Xiong et al, 2020;Du et al, 2021) and oral candidiasis (Zhou et al, 2021). Berberine induced a decrease in the viability of C. albicans biofilms with the actions on the integrity of plasma, mitochondrial membranes, and DNA (Da Silva et al, 2016).…”

Section: Mechanisms Of Inhibiting Fungal Biofilm Formationmentioning

confidence: 99%

Natural products from traditional medicine as promising agents targeting at different stages of oral biofilm development

Chi

Wang

et al. 2022

Front. Microbiol.

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Oral cavity is an ideal habitat for more than 1,000 species of microorganisms. The diverse oral microbes form biofilms over the hard and soft tissues in the oral cavity, affecting the oral ecological balance and the development of oral diseases, such as caries, apical periodontitis, and periodontitis. Currently, antibiotics are the primary agents against infectious diseases; however, the emergence of drug resistance and the disruption of oral microecology have challenged their applications. The discovery of new antibiotic-independent agents is a promising strategy against biofilm-induced infections. Natural products from traditional medicine have shown potential antibiofilm activities in the oral cavity with high safety, cost-effectiveness, and minimal adverse drug reactions. Aiming to highlight the importance and functions of natural products from traditional medicine against oral biofilms, here we summarized and discussed the antibiofilm effects of natural products targeting at different stages of the biofilm formation process, including adhesion, proliferation, maturation, and dispersion, and their effects on multi-species biofilms. The perspective of antibiofilm agents for oral infectious diseases to restore the balance of oral microecology is also discussed.

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“…CHK1 and SSK1 mutants had a hypha-forming defect on medium 199 (pH = 7.5), Spider medium, and serum-mediated solid medium. However, they developed hyphae and flocculate extensively in liquid media, possibly due to the false expression of proteins on the cell surface [ 18 , 40 , 44 , 89 , 107 ]. CHK1 mutants can also form hyphae similar to the wild type strain but down-regulate the expression of virulence factors in liquid media when co-cultured with oral epithelial cells, indicating its critical role in oral candidiasis [ 107 ].…”

Section: Functions Of C Albicans Two-component Systemmentioning

confidence: 99%

“…However, they developed hyphae and flocculate extensively in liquid media, possibly due to the false expression of proteins on the cell surface [ 18 , 40 , 44 , 89 , 107 ]. CHK1 mutants can also form hyphae similar to the wild type strain but down-regulate the expression of virulence factors in liquid media when co-cultured with oral epithelial cells, indicating its critical role in oral candidiasis [ 107 ]. Interestingly, cell aggregation occurs not only in liquid media, but also on solid media.…”

Section: Functions Of C Albicans Two-component Systemmentioning

confidence: 99%

The two-component signal transduction system and its regulation in Candida albicans

Liao

Chen

et al. 2021

Virulence

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Candida albicans, which can cause superficial and life-threatening systemic infections, is the most common opportunistic fungal pathogen in the human microbiome. The two-component system is one of the most important C. albicans signal transduction pathways, regulating the response to oxidative and osmotic stresses, adhesion, morphogenesis, cell wall synthesis, virulence, drug resistance, and the host-pathogen interactions. Notably, some components of this signaling pathway have not been found in the human genome, indicating that the two-component system of C. albicans can be a potential target for new antifungal agents. Here, we summarize the composition, signal transduction, and regulation of the two-component system of C. albicans to emphasize its essential roles in the pathogenesis of C. albicans and the new therapeutic target for antifungal drugs.

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Candida albicans CHK1 gene from two-component system is essential for its pathogenicity in oral candidiasis

Cited by 14 publications

References 71 publications

Deletion of Non-histidine Domains of Histidine Kinase CHK1 Diminishes the Infectivity of Candida albicans in an Oral Mucosal Model

Deletion of Non-histidine Domains of Histidine Kinase CHK1 Diminishes the Infectivity of Candida albicans in an Oral Mucosal Model

Natural products from traditional medicine as promising agents targeting at different stages of oral biofilm development

The two-component signal transduction system and its regulation in Candida albicans

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