Chloramphenicol inhibits eukaryotic Ser/Thr phosphatase and infection-specific cell differentiation in the rice blast...

Area of Science:

• Mycology
• Molecular Biology
• Biochemistry

Background:

• Chloramphenicol (Cm) is a broad-spectrum antibiotic effective against prokaryotes but causes unknown severe side effects in eukaryotes.
• The plant pathogen Magnaporthe oryzae causes rice blast disease through a process involving single-cell differentiation to form an appressorium.
• Cm specifically inhibits appressorium formation in M. oryzae, suggesting novel molecular targets in this fungus.

Purpose of the Study:

• To identify the molecular target(s) of Chloramphenicol (Cm) in the rice blast fungus Magnaporthe oryzae.
• To investigate the role of the putative Cm target, MoDullard, in fungal development and pathogenicity.
• To explore potential eukaryotic targets of Cm based on conserved protein function.

Main Methods:

• T7 phage display was employed to identify potential Cm-binding proteins.
• In vivo and in vitro experiments were conducted to assess the function of MoDullard and its interaction with Cm.
• Functional complementation assays using human phosphatase CTDSP1 were performed.

Main Results:

• The Ser/Thr-protein phosphatase MoDullard was identified as a potential target of Cm in M. oryzae.
• MoDullard is essential for appressorium formation in M. oryzae.
• Cm directly binds to and inhibits MoDullard activity.
• Human CTDSP1 can functionally complement MoDullard during appressorium formation.

Conclusions:

• MoDullard is a novel molecular target of Chloramphenicol (Cm) in the rice blast fungus, essential for appressorium formation.
• The findings suggest that Cm may target homologous phosphatases in eukaryotes, potentially explaining its toxicity.
• Human CTDSP1's ability to complement MoDullard highlights a conserved function and a potential eukaryotic target for Cm.