Deletion of the putative stretch-activated ion channel Mid1 is hypervirulent in Aspergillus fumigatus

Jiang, Hechun; Shen, Ya; Liu, Weida; Lü, Ling

doi:10.1016/j.fgb.2013.11.003

Cited by 54 publications

(42 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As the biotroph C. purpurea and hemibiotroph G. zeae both colonize live host tissues to establish infection, possibly experiencing calcium limiting conditions, while the necrotroph B. cinerea rapidly induces host cell death ahead of infection and may not rely on the HACS. Recently, Jiang et al [63] characterized the A. fumigatus Mid1 homologue. The phenotypes shown for the afmid1 null mutant mostly agreed with what was observed in the presented study.…”

Section: Discussionmentioning

confidence: 99%

The Involvement of the Mid1/Cch1/Yvc1 Calcium Channels in Aspergillus fumigatus Virulence

et al. 2014

View full text Add to dashboard Cite

Aspergillus fumigatus is a major opportunistic pathogen and allergen of mammals. Calcium homeostasis and signaling is essential for numerous biological processes and also influences A. fumigatus pathogenicity. The presented study characterized the function of the A. fumigatus homologues of three Saccharomyces cerevisiae calcium channels, voltage-gated Cch1, stretch-activated Mid1 and vacuolar Yvc1. The A. fumigatus calcium channels cchA, midA and yvcA were regulated at transcriptional level by increased calcium levels. The YvcA::GFP fusion protein localized to the vacuoles. Both ΔcchA and ΔmidA mutant strains showed reduced radial growth rate in nutrient-poor minimal media. Interestingly, this growth defect in the ΔcchA strain was rescued by the exogenous addition of CaCl2. The ΔcchA, ΔmidA, and ΔcchA ΔmidA strains were also sensitive to the oxidative stress inducer, paraquat. Restriction of external Ca2+ through the addition of the Ca2+-chelator EGTA impacted upon the growth of the ΔcchA and ΔmidA strains. All the A. fumigatus ΔcchA, ΔmidA, and ΔyvcA strains demonstrated attenuated virulence in a neutropenic murine model of invasive pulmonary aspergillosis. Infection with the parental strain resulted in a 100% mortality rate at 15 days post-infection, while the mortality rate of the ΔcchA, ΔmidA, and ΔyvcA strains after 15 days post-infection was only 25%. Collectively, this investigation strongly indicates that CchA, MidA, and YvcA play a role in A. fumigatus calcium homeostasis and virulence.

show abstract

Section: Discussionmentioning

confidence: 99%

The Involvement of the Mid1/Cch1/Yvc1 Calcium Channels in Aspergillus fumigatus Virulence

et al. 2014

View full text Add to dashboard Cite

show abstract

“…All strains of A. fumigatus used in this study are given in Table 1. Generally, A. fumigatus strains were grown on YAG-or YUU (YAG supplemented with 5 mM uridine and 10 mM uracil)-rich medium, according to Jiang et al, which contained 2% glucose, 0.5% yeast extract, and 1 ml/liter 1,000ϫ trace elements (38). To test the sensitivity of A. fumigatus to stresses, NaCl, D-sorbitol, H 2 O 2 , menadione, Congo red, calcofluor white, itraconazole, voriconazole, terbinafine, amphotericin B, and caspofungin were supplemented in the YAG or YUU medium.…”

Section: Methodsmentioning

confidence: 99%

Erg4A and Erg4B Are Required for Conidiation and Azole Resistance via Regulation of Ergosterol Biosynthesis in Aspergillus fumigatus

Long

Zeng

et al. 2017

Appl Environ Microbiol

Self Cite

View full text Add to dashboard Cite

Ergosterol, a fungus-specific sterol enriched in cell plasma membranes, is an effective antifungal drug target. However, current knowledge of the ergosterol biosynthesis process in the saprophytic human fungal pathogen Aspergillus fumigatus remains limited. In this study, we found that two endoplasmic reticulumlocalized sterol C-24 reductases encoded by both erg4A and erg4B homologs are required to catalyze the reaction during the final step of ergosterol biosynthesis. Loss of one homolog of Erg4 induces the overexpression of the other one, accompanied by almost normal ergosterol synthesis and wild-type colony growth. However, double deletions of erg4A and erg4B completely block the last step of ergosterol synthesis, resulting in the accumulation of ergosta-5,7,22,24(28)-tetraenol, a precursor compound of ergosterol. Further studies indicate that erg4A and erg4B are required for conidiation but not for hyphal growth. Importantly, the Δerg4A Δerg4B mutant still demonstrates wild-type virulence in a compromised mouse model but displays remarkable increased susceptibility to antifungal azoles. Our data suggest that inhibitors of Erg4A and Erg4B may serve as effective candidates for adjunct antifungal agents with azoles.IMPORTANCE Knowledge of the ergosterol biosynthesis pathway in the human opportunistic pathogen A. fumigatus is useful for designing and finding new antifungal drugs. In this study, we demonstrated that the endoplasmic reticulum-localized sterol C-24 reductases Erg4A and Erg4B are required for conidiation via regulation of ergosterol biosynthesis. Moreover, inactivation of both Erg4A and Erg4B results in hypersensitivity to the clinical guideline-recommended antifungal drugs itraconazole and voriconazole. Therefore, our finding indicates that inhibition of Erg4A and Erg4B might be an effective approach for alleviating A. fumigatus infection.

show abstract

“…Consistent with the defect of DFoCCH1 and DFoMID1 in hyphal morphology and growth, loss of the FoMID1 ortholog in Claviceps purpurea caused a defect in accumulating cell wall polysaccharides at hyphal tips (Bormann and Tudzynski, 2009). Disruption of the MID1 ortholog in Aspergillus fumigatus also caused irregular distribution of septa and nuclei (Jiang et al, 2014). These observations suggest that MID1 orthologs are involved in guiding transport and deposition of vesicles carrying cell wall materials.…”

Section: Discussionmentioning

confidence: 86%

“…The orthologs of FoCCH1, FoMID1 and FoYVC1 have been characterized in other filamentous fungi (Cavinder et al, 2011;de Castro et al, 2014;Hallen and Trail, 2008;Harren and Tudzynski, 2013;Jiang et al, 2014;Lew et al, 2008). Severe growth retardation of Botrytis cinerea cch1 and mid1 deletion mutants in minimal medium was alleviated by increasing the amount of CaCl 2 in the medium (Harren and Tudzynski, 2013).…”

Section: Discussionmentioning

confidence: 99%

“…Both CCH1 and MID1 have been shown to be required for the extracellular Ca 2+ uptake in response to mating pheromone and also are involved in iron and cold tolerance in yeast (Peiter et al, 2005). In several filamentous fungi, CCH1 and MID1 orthologs have been shown to be important role for vegetative growth and development (Cavinder et al, 2011;de Castro, 2014;Hallen and Trail, 2008;Harren and Tudzynski, 2013;Jiang et al, 2014;Lew et al, 2008). The YVC1 channel, a homolog of the animal transient receptor potential protein 2, resides in the vacuolar membrane and participates in controlling vacuolar pressure (Chang et al, 2010;Palmer et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Roles of three Fusarium oxysporum calcium ion (Ca2+) channels in generating Ca2+ signatures and controlling growth

Kim

Frailey

et al. 2015

Fungal Genetics and Biology

View full text Add to dashboard Cite

Deletion of the putative stretch-activated ion channel Mid1 is hypervirulent in Aspergillus fumigatus

Cited by 54 publications

References 46 publications

The Involvement of the Mid1/Cch1/Yvc1 Calcium Channels in Aspergillus fumigatus Virulence

The Involvement of the Mid1/Cch1/Yvc1 Calcium Channels in Aspergillus fumigatus Virulence

Erg4A and Erg4B Are Required for Conidiation and Azole Resistance via Regulation of Ergosterol Biosynthesis in Aspergillus fumigatus

Roles of three Fusarium oxysporum calcium ion (Ca2+) channels in generating Ca2+ signatures and controlling growth

Contact Info

Product

Resources

About