Anti-infective and cytotoxic activities of marine fungi derived from Philippine macroalgae and seagrasses

Marine-derived fungi (MDF) are promising sources of bioactive chemicals [1 – 3]. This study investigates the potential of MDF isolated from macroalgae and seagrasses in producing bioactive metabolites. The isolated MDF belonged to the genera Aspergillus, Fusarium, Paecilomyces, Penicillium, Sclerotinia, Thamnidium, and Trichoderma. Crude culture extracts of selected MDF were partially active (10 – 13 mm ZOI) to active (14 – 19 mm ZOI) against Pseudomonas aeruginosa and Staphylococcus aureus while cytotoxicity (LD₅₀) against the brine shrimp Artemia salina nauplii ranged from 201.56 – 948.37 µg/mL. The result of the screening led to the selection of five bioactive morphospecies, all belonging to the genus Aspergillus as inferred by sequencing their β-tubulin gene. These marine aspergilli were mass produced in different culture media and screened for their trypanocidal activity and cytotoxicity against cancer cells. For cytotoxicity, A. tubingensis cultivated in potato dextrose broth with salt showed to be the most active against P388 (IC₅₀: 1,028 ng/mL) and HeLa (IC₅₀: 1,301 ng/mL). For trypanocidal activity, A. fumigatus cultivated in malt extract broth without salt showed to be the most promising (IC₅₀: 298.18 ng/mL). Given the chemotherapeutic potential of A. tubingensis, bioactivity-guided isolation of its active component was carried out. TOF-MS and ¹H NMR identified the bioactive compound as malformin A₁, a known cyclic pentapeptide [4,5]. Biological profiling revealed that malformin A₁ exhibits trypanocidal activity (IC₅₀: 28.44 nM) and cytotoxicity against HeLa (IC₅₀: 94.59 nM) and P388 (IC₅₀: 132.74 nM). The compound was also selective for Trypanosoma congolense (selectivity index value: 3.33 – 4.67). Immunofluorescence staining was also performed to follow the histone modifications induced by the compound in HeLa. Interestingly, the compound induced repressive levels of H3K27me3, H3K27ac and H4K5ac and enhanced levels of H3K9me2, H3K9me3 and H4K16ac.

Acknowledgements: The authors would like to acknowledge the assistance of Dr. Frederick Vande Vusse for the collection of host algae and of Dr. Paciente Cordero and Dr. Irineo Dogma for the aid in the identification of host algae and fungi, and to the Department of Science and Technology-Science Education Institute for the ASTHRDP graduate scholarship and thesis grant.

Keywords: fungal natural products, marine fungi, cytotoxicity, anti-infective.

References:

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