AUTHOR=Ouyang Xudong , Hoeksma Jelmer , Beenker Wouter A.G. , van der Beek Samantha , den Hertog Jeroen 

TITLE=Harzianic acid exerts antimicrobial activity against Gram-positive bacteria and targets the cell membrane

JOURNAL=Frontiers in Microbiology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2024.1332774

DOI=10.3389/fmicb.2024.1332774

ISSN=1664-302X

ABSTRACT=<p>The thermophilic fungus <italic>Oidiodendron flavum</italic> is a saprobe that is commonly isolated from soil. Here, we identified a Gram-positive bacteria-selective antimicrobial secondary metabolite from this fungal species, harzianic acid (HA). Using <italic>Bacillus subtilis</italic> strain 168 combined with dynamic bacterial morphology imaging, we found that HA targeted the cell membrane. To further study the antimicrobial activity of HA, we isolated an HA-resistant strain, <italic>Bacillus subtilis</italic> strain M9015, and discovered that the mutant had more translucent colonies than the wild type strain, showed cross resistance to rifampin, and harbored five mutations in the coding region of four distinct genes. Further analysis of these genes indicated that the mutation in <italic>atpE</italic> might be responsible for the translucency of the colonies, and mutation in <italic>mdtR</italic> for resistance to both HA and rifampin. We conclude that HA is an antimicrobial agent against Gram-positive bacteria that targets the cell membrane.</p>