Phosphoglucose Isomerase Is Important for Aspergillus fumigatus Cell Wall Biogenesis

Abstract

Aspergillus fumigatus is an opportunistic fungal pathogen causing deadly infections in immunocompromised patients. Enzymes essential for fungal survival and cell wall biosynthesis are considered potential drug targets against A. fumigatus .

Phosphomannose Isomerase Is Involved in Development, Stress Responses, and Pathogenicity of Aspergillus flavus

“…Nonconserved sites of the target could be explored for selectivity, such as the selective inhibitors against Plasmodium falciparum N -myristoyltransferase (NMT) that were developed based only on the single-residue difference from human orthologue ( 47 , 48 ). Recently, we also confirmed that A. fumigatus phosphoglucose isomerase (PGI) possesses an exploitable site and space for developing selective inhibitors ( 49 ). Applying PMI inhibitors in the agricultural field will be more reachable since the PMIs are less ubiquitous in the kingdom Plantae and are reported absent in many plants ( 27 ).…”

Central Sugar Metabolism and the Cell Wall

“…With regard to the deteriorated conidiation, germination, and hyphal growth exhibited by the Δ pgi mutant, the study by Zhou and coworkers ( 14 ) also revealed the concept that sugar metabolism and cell wall biosynthesis functions are tightened together during growth and morphogenesis ( Fig. 1 ).…”

“…How PGI regulates fungal morphogenesis and how it affects the cell wall remain very fuzzy. In order to address these questions, Zhou et al ( 14 ) used for the first time the human pathogenic filamentous fungus A. fumigatus .…”

“…In their manuscript, the authors characterized the pgi null mutant (Δ pgi ) in A. fumigatus and embraced two intertwined functions of the A. fumigatus PGI ( Af PGI) in (i) sugar metabolism and (ii) cell wall biosynthesis, which were compelling enough to explore the role of PGI in virulence and to solve its crystal structure ( 14 ) ( Fig. 1 ).…”

“…1 ). As such, it was unsurprising that the deletion of Afpgi engendered higher sensitivity to caspofungin and Congo red ( 14 ). Similar findings were recently reported in Lentinula edodes , in which silencing of pgi entailed decreased expression of genes involved in β-1,3-glucan synthesis, whereas genes related to chitin synthesis were upregulated, all along with increased sensitivity to cell wall-disrupting agents ( 15 ).…”