Antimicrobial Natural Products from Plant Pathogenic Fungi

Abstract

Isolates of a variety of fungal plant pathogens (Alternaria radicina ICMP 5619, Cercospora beticola ICMP 15907, Dactylonectria macrodidyma ICMP 16789, D. torresensis ICMP 20542, Ilyonectria europaea ICMP 16794, and I. liriodendra ICMP 16795) were screened for antimicrobial activity against the human pathogenic bacteria Acinetobacter baumannii, Pseudomonas aeruginosa, Escherichia coli, Mycobacterium abscessus, and M. marinum and were found to have some activity. Investigation of the secondary metabolites of these fungal isolates led to the isolation of ten natural products (1-10) of which one was novel, (E)-4,7-dihydroxyoct-2-enoic acid (1). Structure elucidation of all natural products was achieved by a combination of NMR spectroscopy and mass spectrometry. We also investigated the antimicrobial activity of a number of the isolated natural products. While we did not find (E)-4,7-dihydroxyoct-2-enoic acid (1) to have any activity against the bacteria and fungi in our assays, we did find that cercosporin (7) exhibited potent activity against Methicillin resistant Staphylococcus aureus (MRSA), dehydro-curvularin (6) and radicicol (10) exhibited antimycobacterial activity against M. marinum, and brefeldin A (8) and radicicol (10) exhibited antifungal activity against Candida albicans. Investigation of the cytotoxicity and haemolytic activities of these natural products (6-8 and 10) found that only one of the four active compounds, radicicol (10), was non-cytotoxic and non-haemolytic.

Keywords: Candida albicans; Staphylocccus aureus; antibacterial activity; fungal plant pathogens; isolation; metabolites; mycobacteria; natural product.

Figure 1

Antibacterial activity of ICMP 5619, 15907, 16789, 16794, 16795, and 20542 against A. baumannii, E. coli, M. abscessus, M. marinum, and P. aeruginosa. Data are presented as box and whisker plots of the activity scores. The solid line shown at 0 is the median control value while the dotted line at 1 is the activity threshold. Scores above 1 correspond to a >90% reduction in bacterial bioluminescence compared to the corresponding no-fungi control. Similarly, an activity score above 2 corresponds to a >99% reduction.

Figure 2

Structures of the isolated natural products 1–10.

Figure 3

Selected COSY correlations (blue) and HMBC correlations (red) for 1.

Figure 4

Antimycobacterial activity of compounds 1, 2, and 4–10 against M. abscessus BSG301 and M. marinum BSG101. Data are presented as box and whisker plots of activity scores. The solid line shown at 0 is the median control value while the dotted line at 1 is the activity threshold. Scores above 1 correspond to a >90% reduction in bacterial bioluminescence compared to the corresponding no-fungi control. Similarly, an activity score above 2 corresponds to a >99% reduction.