The MAPK Hog1 mediates the response to amphotericin B in Candida albicans

Guirao-Abad, José P.; Sánchez-Fresneda, Ruth; Román, Elvira; Pla, Jesús; Argüelles, Juan-Carlos; Alonso-Monge, Rebeca

doi:10.1016/j.fgb.2019.103302

Cited by 16 publications

(13 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This was hypothesized to be due to the involvement of Yck2 in responding to cell wall stress, with inhibitor treatment or genetic depletion leading to an upregulation of cell wall proteins and damage genes ( Caplan et al., 2020 ). Finally, in addition to the role of the HOG MAPK cascade in upregulating chitin synthesis upon exposure to cell wall stress, Hog1 also plays important roles on governing responses to amphotericin B in both C. albicans and C. auris ( Guirao-Abad et al., 2020 ; Shivarathri et al., 2020 ).…”

Section: Stress Response Regulatorsmentioning

confidence: 99%

The role of Candida albicans stress response pathways in antifungal tolerance and resistance

2022

View full text Add to dashboard Cite

Section: Stress Response Regulatorsmentioning

confidence: 99%

The role of Candida albicans stress response pathways in antifungal tolerance and resistance

2022

View full text Add to dashboard Cite

“…4). These preliminary data support the introduction of antibiotic lock therapy to eradicate active fungal biofilms that adhere on indwelling medical devices [27,[32][33][34][35].…”

Section: Level Of Biofilm Formation In Trehalase-deficient Mutant Of ...mentioning

confidence: 54%

“…Among other therapeutic strategies, several groups have explored the introduction of biochemical and genetic alterations in several key nutritional pathways as potentially interesting antifungal targets [12,13,15]. In fact, Amphotericin B-induced fungicidal effect on C. albicans is mediated by the Hog1 pathway [27]. In this context, enzymes involved in trehalose metabolism have been chosen as a preferential candidate to target new antifungals [14,16], since this disaccharide is absent in mammals and plays an important role as a virulence factor in prevalent pathogenic fungi, including a consistent defensive response against clinical antifungals [31].…”

Section: Discussionmentioning

confidence: 99%

“…Induction of internal oxidative stress acts as an additional component of the fungicidal effect triggered by some antifungals, i.e Amphotericin B, against highly prevalent pathogenic yeasts such as Candida species, although this mechanism does not appear to be operative with other agents examined, like Micafungin [26,27]. However, the universal validity of this factor has yet to be extended to other members of the antibiotic and drugs families endowed with antifungal activity, as well as against other important infectious fungi, like Aspergillus or Cryptococcus [24,28,29].…”

Section: Level Of Ros Formation and Mitochondrial Activity After Addi...mentioning

confidence: 99%

See 1 more Smart Citation

Lack of Functional Trehalase Activity in Candida Parapsilosis Increases Susceptibility to Itraconazole

Sánchez-Fresneda¹,

Muñoz-Megías²,

Guirao³

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

Central metabolic pathways may play a major role in the virulence of pathogenic fungi. Here, we have investigated the susceptibility of a Candida parapsilosis mutant deficient in trehalase activity (atc1Δ/ntc1Δ strain) to the azolic compounds Fluconazole and Itraconazole. A time-course exposure to Itraconazole but not Fluconazole induced a significant degree of cell-killing in mutant cells compared to the parental strain. Flow cytometry determinations indicated that Itraconazole was able to induce a marked production of endogenous ROS together with a simultaneous increase in membrane potential, these effects being irrelevant after Fluconazole addition. Furthermore, only Itraconazole induced a significant synthesis of endogenous trehalose. The recorded impaired capacity of mutant cells to produce structured biofilms was further increased in the presence of both azoles, with Itraconazole being more effective than Fluconazole. Our results in the opportunistic pathogen yeast C. parapsilosis reinforce the study of trehalose metabolism as an attractive therapeutic target and allow extending the hypothesis that the generation of internal oxidative stress may be a component of the antifungal action exerted by the compounds currently available in medical practice.

show abstract

“…Our results are in agreement with this, as strains defective in HOG1 (which are highly susceptible to oxidative stress), are also sensitive to these antifungals. It has recently been shown that treatment with amphotericin B results in the phosphorylation of Hog1 and that the absence of this stress kinase increases fungal susceptibility to this antifungal compound [58]. Strikingly, cek1, cek2 and cek1 cek2 double mutants were consistently less susceptible to amphotericin B.…”

Section: Discussionmentioning

confidence: 99%

Characterization of a Candida albicans Mutant Defective in All MAPKs Highlights the Major Role of Hog1 in the MAPK Signaling Network

Correia

Wilson

Hube

et al. 2020

JoF

Self Cite

View full text Add to dashboard Cite

The success of Candida albicans as a pathogen relies on its ability to adapt and proliferate in different environmental niches. Pathways regulated by mitogen-activated protein kinases (MAPKs) are involved in sensing environmental conditions and developing an accurate adaptive response. Given the frequent cooperative roles of these routes in cellular functions, we have generated mutants defective in all combinations of the four described MAPKs in C. albicans and characterized its phenotype regarding sensitiveness to specific drugs, morphogenesis and interaction with host immune cells. We demonstrate that all MAPKs are dispensable in this yeast as a mutant defective in Cek1, Cek2, Mkc1 and Hog1 is viable although highly sensitive to oxidative and osmotic stress, displaying a specific pattern of sensitivity to antifungals. By comparing its phenotype with single, double and triple combinations of MAPK-deletion mutants we were able to unveil a Cek1-independent mechanism for Hog1 resistance to Congo red, and confirm the predominant effect of Hog1 on oxidative and osmotic adaptation. The quadruple mutant produces filaments under non-inducing conditions, but is unable to develop chlamydospores. Furthermore, cek1 cek2 mkc1 hog1 cells switch to the opaque state at high frequency, which is blocked by the ectopic expression of HOG1 suggesting a role of this kinase for phenotypic switching.

show abstract

The MAPK Hog1 mediates the response to amphotericin B in Candida albicans

Cited by 16 publications

References 35 publications

The role of Candida albicans stress response pathways in antifungal tolerance and resistance

The role of Candida albicans stress response pathways in antifungal tolerance and resistance

Lack of Functional Trehalase Activity in Candida Parapsilosis Increases Susceptibility to Itraconazole

Characterization of a Candida albicans Mutant Defective in All MAPKs Highlights the Major Role of Hog1 in the MAPK Signaling Network

Contact Info

Product

Resources

About