The high osmolarity glycerol (HOG) pathway in fungi^†

A host defense peptide mimetic, brilacidin, potentiates caspofungin antifungal activity against human pathogenic fungi

“…Considering the importance of calcineurin in the signaling response to A. fumigatus osmotic stress and the cell wall integrity pathway (da Silva Ferreira et al ., 2007; Ries et al ., 2017; de Castro et al ., 2014, 2019) and the fact that PAKs have been shown to be involved in signaling through MAPK pathways (Boyce and Andrianopoulos, 2011), we tested the BRI growth inhibition of four A. fumigatus null mutants for MAPK Δ sakA , Δ mpkC , Δ mpkB and Δ mpkA which regulate osmotic stress and CWI pathways responses (Brown and Goldman, 2016; Yaakoub et al ., 2021). We identified only Δ mpkA as being more sensitive to BRI 20 µM (Supplementary Table S3).…”

“…fumigatus null mutants for MAPK ΔsakA, ΔmpkC, ΔmpkB and ΔmpkA which regulate osmotic stress and CWI pathways responses (Brown and Goldman, 2016;Yaakoub et al, 2021). We identified only ΔmpkA as being more sensitive to BRI 20 µM (Supplementary Table S3).…”

“…have been shown to be involved in signaling through MAPK pathways (Boyce and Andrianopoulos, 2011), we tested the BRI growth inhibition of four A. fumigatus null mutants for MAPK ΔsakA, ΔmpkC, ΔmpkB and ΔmpkA which regulate osmotic stress and CWI pathways responses (Brown and Goldman, 2016;Yaakoub et al, 2021). We identified only ΔmpkA as being more sensitive to BRI 20 µM (Supplementary Table S3).…”

SAKrificing an Essential Stress-Sensing Pathway Improves Aspergillus fumigatus Germination

“…1 ). In this regard, several studies have demonstrated the pivotal role of the HOG signaling pathway in stress adaptation and virulence in prominent yeast pathogens such as Candida albicans and Cryptococcus neoformans , and also A. fumigatus ( 11 – 14 ). In these models and upon diverse stressing conditions, the HOG pathway is activated and corresponds to the sequential phosphorylation of MAPKs involving SskB (MAPKKK), Pbs2 (MAPKK), and finally a couple of paralogous MAPK, i.e., SakA and MpkC ( 13 ).…”

Central Sugar Metabolism and the Cell Wall

“…Salvage pathways to compensate for the halt of glucan production by upregulation of the other components have been repeatedly shown in the past ( 1 ). The high-osmolarity glycerol pathway and the cell wall integrity pathway constitute potential candidates, since both pathways are specifically rewired together toward cell wall-related functions in A. fumigatus , including biosynthesis and remodeling ( 16 ). Identification of the salvage pathway compensating for the lack of Af PGI and thereby its inhibitors may help circumvent the drawback of echinocandins, perhaps using combinatorial approaches.…”