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

Abstract

ABSTRACT Aspergillus flavus causes invasive aspergillosis in immunocompromised patients and severe contamination of agriculturally important crops by producing aflatoxins. The fungal cell wall is absent in animals and is structurally different from that of plants, which makes it a potential antifungal drug target due to its essentiality for fungal survival. Mannose is one of the important components in the fungal cell wall, which requires GDP-mannose (GDP-Man) as the primary donor. Three consecutive enzymes, namely, phosphomannose isomerase (PMI), phosphomannose mutase (PMM), and GDP-mannose phosphorylase (GMPP), are required for GDP-Man biosynthesis. Thus, PMI is of prime importance in cell wall biosynthesis and also has an active role in sugar metabolism. Here, we investigated the functional role of PMI in A. flavus by generating a pmiA-deficient strain. The mutant required exogenous mannose to survive and exhibited reduced growth rate, impaired conidiation, early germination, disturbance in stress responses, and defects in colonization of crop seeds. Furthermore, attenuated virulence of the mutant was documented in both Caenorhabditis elegans and Galleria mellonella infection models. Our results suggested that PMI plays an important role in the development, stress responses, and pathogenicity of A. flavus and therefore could serve as a potential target for battling against infection and controlling aflatoxin contamination caused by A. flavus. IMPORTANCE Aspergillus flavus is a common fungal pathogen of humans, animals, and agriculturally important crops. It causes invasive aspergillosis in humans and also produces highly carcinogenic mycotoxins in postharvest crops that threaten food safety worldwide. To alleviate or eliminate the threats posed by A. flavus, it is necessary to identify genes involved in pathogenicity and mycotoxin contamination. However, little progress has been made in this regard. Here, we focused on PMI, which is the first enzyme involved in the biosynthesis pathway of GDP-Man and thus is important for cell wall synthesis and protein glycosylation. Our study revealed that PMI is important for growth of A. flavus. It is also involved in conidiation, germination, morphogenesis, stress responses, and pathogenicity of A. flavus. Thus, PMI is a potent antifungal target to curb the threats posed by A. flavus.

Keywords

• Aspergillus flavus
• drug target
• pathogenicity
• phosphomannose isomerase
• stress response