scholarly journals The Fungicidal Action of Micafungin is Independent on Both Oxidative Stress Generation and HOG Pathway Signaling in Candida albicans

2020 ◽  
Vol 8 (12) ◽  
pp. 1867
Author(s):  
Rebeca Alonso-Monge ◽  
José P. Guirao-Abad ◽  
Ruth Sánchez-Fresneda ◽  
Jesús Pla ◽  
Genoveva Yagüe ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Candida Albicans ◽  
Parental Strain ◽  
Antioxidant Activities ◽  
Positive Control ◽  
Mitogen Activated Protein Kinase ◽  
Stress Generation ◽  
Hog Pathway ◽  
Fungicidal Action ◽  
Mitogen Activated Protein

In fungi, the Mitogen-Activated Protein kinase (MAPK) pathways sense a wide variety of environmental stimuli, leading to cell adaptation and survival. The HOG pathway plays an essential role in the pathobiology of Candida albicans, including the colonization of the gastrointestinal tract in a mouse model, virulence, and response to stress. Here, we examined the role of Hog1 in the C. albicans response to the clinically relevant antifungal Micafungin (MF), whose minimum inhibitory concentration (MIC) was identical in the parental strain (RM100) and in the isogenic homozygous mutant hog1 (0.016 mg/L). The cell viability was impaired without significant differences between the parental strain, the isogenic hog1 mutant, and the Hog1+ reintegrant. This phenotype was quite similar in a collection of hog1 mutants constructed in a different C. albicans background. MF-treated cells failed to induce a relevant increase of both reactive oxygen species (ROS) formation and activation of the mitochondrial membrane potential in parental and hog1 cells. MF was also unable to trigger any significant activation of the genes coding for the antioxidant activities catalase (CAT1) and superoxide dismutase (SOD2), as well as on the corresponding enzymatic activities, whereas a clear induction was observed in the presence of Amphotericin B (AMB), introduced as a positive control of Hog1 signaling. Furthermore, Hog1 was not phosphorylated by the addition of MF, but, notably, this echinocandin caused Mkc1 phosphorylation. Our results strongly suggest that the toxic effect of MF on C. albicans cells is not mediated by the Hog1 MAPK and is independent of the generation of an internal oxidative stress in C. albicans.

scholarly journals Histatin 5 Initiates Osmotic Stress Response in Candida albicans via Activation of the Hog1 Mitogen-Activated Protein Kinase Pathway

2007 ◽  
Vol 6 (10) ◽  
pp. 1876-1888 ◽  
Author(s):  
Slavena Vylkova ◽  
Woong Sik Jang ◽  
Wansheng Li ◽  
Namrata Nayyar ◽  
Mira Edgerton
Keyword(s):  
Oxidative Stress ◽  
Candida Albicans ◽  
Stress Response ◽  
Protein Kinase ◽  
Osmotic Stress ◽  
Mitogen Activated Protein Kinase ◽  
Dependent Manner ◽  
Hog Pathway ◽  
Histatin 5 ◽  
Mitogen Activated Protein

ABSTRACT Histatin 5 (Hst 5) is a salivary cationic peptide that has toxicity for Candida albicans by inducing rapid cellular ion imbalance and cell volume loss. Microarray analyses of peptide-treated cells were used to evaluate global gene responses elicited by Hst 5. The major transcriptional response of C. albicans to Hst 5 was expression of genes involved in adaptation to osmotic stress, including production of glycerol (RHR2, SKO1, and PDC11) and the general stress response (CTA1 and HSP70). The oxidative-stress genes AHP1, TRX1, and GPX1 were mildly induced by Hst 5. Cell defense against Hst 5 was dependent on the Hog1 mitogen-activated protein kinase (MAPK) pathway, since C. albicans hog1/hog1 mutants were significantly hypersensitive to Hst 5 but not to Mkc1 MAPK or Cek1 MAPK mutants. Activation of the high-osmolarity glycerol (HOG) pathway was demonstrated by phosphorylation of Hog1 MAPK as well as by glycerol production following Hst 5 treatment in a dose-dependent manner. C. albicans cells prestressed with sorbitol were less sensitive to subsequent Hst 5 treatment; however, cells treated concurrently with osmotic stress and Hst 5 were hypersensitive to Hst 5. In contrast, cells subjected to oxidative stress had no difference in sensitivity to Hst 5. These results suggest a common underlying cellular response to osmotic stress and Hst 5. The HOG stress response pathway likely represents a significant and effective challenge to physiological levels of Hst 5 and other toxic peptides in fungal cells.

scholarly journals Msb2 Signaling Mucin Controls Activation of Cek1 Mitogen-Activated Protein Kinase in Candida albicans

2009 ◽  
Vol 8 (8) ◽  
pp. 1235-1249 ◽  
Author(s):  
Elvira Román ◽  
Fabien Cottier ◽  
Joachim F. Ernst ◽  
Jesús Pla
Keyword(s):  
Cell Wall ◽  
Candida Albicans ◽  
Protein Kinase ◽  
Osmotic Shock ◽  
Mitogen Activated Protein Kinase ◽  
Hog Pathway ◽  
High Osmolarity ◽  
Cell Wall Biogenesis ◽  
Solid Media ◽  
Mitogen Activated Protein

ABSTRACT We have characterized the role that the Msb2 protein plays in the fungal pathogen Candida albicans by the use of mutants defective in the putative upstream components of the HOG pathway. Msb2, in cooperation with Sho1, controls the activation of the Cek1 mitogen-activated protein kinase under conditions that damage the cell wall, thus defining Msb2 as a signaling element of this pathway in the fungus. msb2 mutants display altered sensitivity to Congo red, caspofungin, zymolyase, or tunicamycin, indicating that this protein is involved in cell wall biogenesis. Msb2 (as well as Sho1 and Hst7) is involved in the transmission of the signal toward Cek1 mediated by the Cdc42 GTPase, as revealed by the use of activated alleles (Cdc42G12V) of this protein. msb2 mutants have a stronger defective invasion phenotype than sho1 mutants when tested on certain solid media that use mannitol or sucrose as a carbon source or under hypoxia. Interestingly, Msb2 contributes to growth under conditions of high osmolarity when both branches of the HOG pathway are altered, as triple ssk1 msb2 sho1 mutants (but not any single or double mutant) are osmosensitive. However, this phenomenon is independent of the presence of Hog1, as Hog1 phosphorylation, Hog1 translocation to the nucleus, and glycerol accumulation are not affected in this mutant following an osmotic shock. These results reveal essential functions in morphogenesis, invasion, cell wall biogenesis, and growth under conditions of high osmolarity for Msb2 in C. albicans and suggest the divergence and specialization of this signaling pathway in filamentous fungi.

scholarly journals The MAP kinase signal transduction network in Candida albicans

Microbiology ◽  
2006 ◽  
Vol 152 (4) ◽  
pp. 905-912 ◽  
Author(s):  
R. Alonso Monge ◽  
E. Román ◽  
C. Nombela ◽  
J. Pla
Keyword(s):  
Signal Transduction ◽  
Cell Wall ◽  
Candida Albicans ◽  
Map Kinases ◽  
Mitogen Activated Protein Kinase ◽  
Phenotypic Characterization ◽  
Cell Integrity ◽  
Hog Pathway ◽  
Chlamydospore Formation ◽  
Mitogen Activated Protein

MAP (mitogen-activated protein) kinase-mediated pathways are key elements in sensing and transmitting the response of cells to environmental conditions by the sequential action of phosphorylation events. In the fungal pathogen Candida albicans, different routes have been identified by genetic analysis, and especially by the phenotypic characterization of mutants altered in the Mkc1, Cek1/2 and Hog1 MAP kinases. The cell integrity (or MKC1-mediated) pathway is primarily involved in the biogenesis of the cell wall. The HOG pathway participates in the response to osmotic stress while the Cek1 pathway mediates mating and filamentation. Their actual functions are, however, much broader and Mkc1 senses several types of stress, while Hog1 is also responsive to other stress conditions and participates in two morphogenetic programmes: filamentation and chlamydospore formation. Furthermore, it has been recently shown that Cek1 participates in a putative pathway involved in the construction of the cell wall and which seems to be operative under basal conditions. As these stimuli are frequently encountered in the human host, they provide a reasonable explanation for the significant reduction in pathogenicity that several signal transduction mutants show in certain animal models of virulence. MAPK pathways therefore represent an attractive multienzymic system for which novel antifungal therapy could be designed.

Age-Related Changes in Activation of Mitogen-Activated Protein Kinase Cascades by Oxidative Stress

1998 ◽  
Vol 3 (1) ◽  
pp. 23-27 ◽  
Author(s):  
Kathryn Z Guyton ◽  
Myriani Gorospe ◽  
Xiantao Wang ◽  
Yolanda D Mock ◽  
Gertrude C Kokkonen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Protein Kinase ◽  
Mitogen Activated Protein Kinase ◽  
Age Related ◽  
Mitogen Activated Protein ◽  
Age Related Changes

scholarly journals The Cek1 and Hog1 Mitogen-Activated Protein Kinases Play Complementary Roles in Cell Wall Biogenesis and Chlamydospore Formation in the Fungal Pathogen Candida albicans

2006 ◽  
Vol 5 (2) ◽  
pp. 347-358 ◽  
Author(s):  
B. Eisman ◽  
R. Alonso-Monge ◽  
E. Román ◽  
D. Arana ◽  
C. Nombela ◽  
...  
Keyword(s):  
Cell Wall ◽  
Candida Albicans ◽  
Map Kinase ◽  
Fungal Pathogen ◽  
Hog Pathway ◽  
Cell Wall Biogenesis ◽  
Chlamydospore Formation ◽  
Mitogen Activated Protein ◽  
Morphological Transitions ◽  
Relationship Of

ABSTRACT The Hog1 mitogen-activated protein (MAP) kinase mediates an adaptive response to both osmotic and oxidative stress in the fungal pathogen Candida albicans. This protein also participates in two distinct morphogenetic processes, namely the yeast-to-hypha transition (as a repressor) and chlamydospore formation (as an inducer). We show here that repression of filamentous growth occurs both under serum limitation and under other partially inducing conditions, such as low temperature, low pH, or nitrogen starvation. To understand the relationship of the HOG pathway to other MAP kinase cascades that also play a role in morphological transitions, we have constructed and characterized a set of double mutants in which we deleted both the HOG1 gene and other signaling elements (the CST20, CLA4, and HST7 kinases, the CPH1 and EFG1 transcription factors, and the CPP1 protein phosphatase). We also show that Hog1 prevents the yeast-to-hypha switch independent of all the elements analyzed and that the inability of the hog1 mutants to form chlamydospores is suppressed when additional elements of the CEK1 pathway (CST20 or HST7) are altered. Finally, we report that Hog1 represses the activation of the Cek1 MAP kinase under basal conditions and that Cek1 activation correlates with resistance to certain cell wall inhibitors (such as Congo red), demonstrating a role for this pathway in cell wall biogenesis.

scholarly journals P38 mitogen-activated protein kinase and Parkinson’s disease

2018 ◽  
Vol 9 (1) ◽  
pp. 147-153 ◽  
Author(s):  
Jianying He ◽  
Wenwen Zhong ◽  
Ming Zhang ◽  
Rongping Zhang ◽  
Weiyan Hu
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Cell Proliferation ◽  
Parkinson's Disease ◽  
Mitogen Activated Protein Kinase ◽  
Pathogenic Role ◽  
Considerable Evidence ◽  
Mitogen Activated Protein ◽  
Neuro Inflammation ◽  
Elder People

AbstractParkinson’s disease, the second major neurodegenerative disease, has created a great impact on the elder people. Although the mechanisms underlying Parkinson’s disease are not fully understood, considerable evidence suggests that neuro-inflammation, oxidative stress, mitochondrial dysfunction, cell proliferation, differentiation and apoptosis are involved in the disease. p38MAPK, an important member of the mitogen-activated protein family, controls several important functions in the cell, suggesting a potential pathogenic role in PD. This review provides a brief description of the role and mechanism of p38MAPK in Parkinson’s disease.

scholarly journals Mitogen-Activated Protein Kinase Hog1 Mediates Adaptation to G1 Checkpoint Arrest during Arsenite and Hyperosmotic Stress

2008 ◽  
Vol 7 (8) ◽  
pp. 1309-1317 ◽  
Author(s):  
Iwona Migdal ◽  
Yulia Ilina ◽  
Markus J. Tamás ◽  
Robert Wysocki
Keyword(s):  
Cell Cycle ◽  
Protein Kinase ◽  
Cell Cycle Arrest ◽  
Kinase Inhibitor ◽  
Hyperosmotic Stress ◽  
Mitogen Activated Protein Kinase ◽  
Hog Pathway ◽  
Cycle Arrest ◽  
Mitogen Activated Protein

ABSTRACT Cells slow down cell cycle progression in order to adapt to unfavorable stress conditions. Yeast (Saccharomyces cerevisiae) responds to osmotic stress by triggering G1 and G2 checkpoint delays that are dependent on the mitogen-activated protein kinase (MAPK) Hog1. The high-osmolarity glycerol (HOG) pathway is also activated by arsenite, and the hog1Δ mutant is highly sensitive to arsenite, partly due to increased arsenite influx into hog1Δ cells. Yeast cell cycle regulation in response to arsenite and the role of Hog1 in this process have not yet been analyzed. Here, we found that long-term exposure to arsenite led to transient G1 and G2 delays in wild-type cells, whereas cells that lack the HOG1 gene or are defective in Hog1 kinase activity displayed persistent G1 cell cycle arrest. Elevated levels of intracellular arsenite and “cross talk” between the HOG and pheromone response pathways, observed in arsenite-treated hog1Δ cells, prolonged the G1 delay but did not cause a persistent G1 arrest. In contrast, deletion of the SIC1 gene encoding a cyclin-dependent kinase inhibitor fully suppressed the observed block of G1 exit in hog1Δ cells. Moreover, the Sic1 protein was stabilized in arsenite-treated hog1Δ cells. Interestingly, Sic1-dependent persistent G1 arrest was also observed in hog1Δ cells during hyperosmotic stress. Taken together, our data point to an important role of the Hog1 kinase in adaptation to stress-induced G1 cell cycle arrest.

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