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A spergillus fumigatus devoid of cell wall β‐1,3‐glucan is viable, massively sheds galactomannan and is killed by septum formation inhibitors
Author(s) -
Dichtl Karl,
Samantaray Sweta,
Aimanianda Vishukumar,
Zhu Zhaojun,
Prévost MarieChristine,
Latgé JeanPaul,
Ebel Frank,
Wagener Johannes
Publication year - 2015
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/mmi.12877
Subject(s) - echinocandins , aspergillus fumigatus , echinocandin , biology , caspofungin , microbiology and biotechnology , glucan , galactomannan , cell wall , mutant , biochemistry , polysaccharide , antifungal , amphotericin b , gene , fluconazole
Summary Echinocandins inhibit β‐1,3‐glucan synthesis and are one of the few antimycotic drug classes effective against A spergillus spp. In this study, we characterized the β‐1,3‐glucan synthase F ks1 of A spergillus fumigatus , the putative target of echinocandins. Data obtained with a conditional mutant suggest that fks1 is not essential. In agreement, we successfully constructed a viable Δ fks1 deletion mutant. Lack of F ks1 results in characteristic growth phenotypes similar to wild type treated with echinocandins and an increased susceptibility to calcofluor white and sodium dodecyl sulfate. In agreement with F ks1 being the only β‐1,3‐glucan synthase in A . fumigatus , the cell wall is devoid of β‐1,3‐glucan. This is accompanied by a compensatory increase of chitin and galactosaminogalactan and a significant decrease in cell wall galactomannan due to a massively enhanced galactomannan shedding. Our data furthermore suggest that inhibition of hyphal septation can overcome the limitations of echinocandin therapy. Compounds inhibiting septum formation boosted the antifungal activity of caspofungin. Thus, development of clinically applicable inhibitors of septum formation is a promising strategy to improve existing antifungal therapy.