Discovery of Anti-MRSA Secondary Metabolites from a Marine-Derived Fungus Aspergillus fumigatus

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA), a WHO high-priority pathogen that can cause great harm to living beings, is a primary cause of death from antibiotic-resistant infections. In the present study, six new compounds, including fumindoline A–C (1–3), 12β, 13β-hydroxy-asperfumigatin (4), 2-epi-tryptoquivaline F (17) and penibenzophenone E (37), and thirty-nine known ones were isolated from the marine-derived fungus Aspergillus fumigatus H22. The structures and the absolute configurations of the new compounds were unambiguously assigned by spectroscopic data, mass spectrometry (MS), electronic circular dichroism (ECD) spectroscopic analyses, quantum NMR and ECD calculations, and chemical derivatizations. Bioactivity screening indicated that nearly half of the compounds exhibit antibacterial activity, especially compounds 8 and 11, and 33–38 showed excellent antimicrobial activities against MRSA, with minimum inhibitory concentration (MIC) values ranging from 1.25 to 2.5 μM. In addition, compound 8 showed moderate inhibitory activity against Mycobacterium bovis (MIC: 25 μM), compound 10 showed moderate inhibitory activity against Candida albicans (MIC: 50 μM), and compound 13 showed strong inhibitory activity against the hatching of a Caenorhabditis elegans egg (IC50: 2.5 μM).

Marine natural products

“…N -Methylated cyclic peptides, asperflomide 312 and asperflosamide 313 were isolated from A. flocculosus 140 and A. fumigatus strains were the source of a steroid 314 , a 2-oxofuranone derivative 315 , indole alkaloids 316 and 317 (as an inseparable mixture), 318 , pseurotin A derivative 319 , 141 alkaloids 320 – 324 , and penibenzophenone E 325 . 142 Gorgonian-derived Aspergillus hiratsukae strains yielded α-pyrone meroterpenoids 326 – 331 , 143 cyclic peptide 332 , ecdysteroid derivative 333 and sesquiterpene lactone 334 , 144 and nitrobenzoyl sesquiterpenoids 335 – 338 , 145 cyclohexadepsipeptides 339 , 340 (ref. 146) and sesquiterpenoids 341 , 342 – 344 (ref.…”

Marine Aspergillus: A Treasure Trove of Antimicrobial Compounds

“…Compounds 66 and 68 showed potent antibacterial activity, and 69 – 74 exhibited strong anti-MRSA activity with MIC values between 1.25 and 2.5 μM. Additionally, compound 66 showed moderate inhibitory activity against Mycobacterium Bovis , with an MIC value of 25 μM, and compound 67 showed moderate inhibitory activity against C. albicans , with an MIC value of 50 μM [ 72 ].…”

“…Nine antimicrobial compounds were isolated from marine fungus A. fumigatus H22. These compounds included 12,13-dihydroxyfumitremorgin C (66), fumitremorgin B (67), 13 (72), penibenzophenone E (73) and sulochrin (74) (Figure 7). Compounds 66 and 68 showed potent antibacterial activity, and 69-74 exhibited strong anti-MRSA activity with MIC values between 1.25 and 2.5 μM.…”

Novel Alkaloids from Aspergillus fumigatus VDL36, an Endophytic Fungus Associated with Vaccinium dunalianum

“…For instance, 12β-hydroxy-13α-methoxyverruculogen TR-2, an indole diketopiperazine alkaloid, exhibited antiphytopathogenic fungi activities . Chaetomine, a quinazoline alkaloid, demonstrates significant cytotoxicity against human leukemia K562 and colon cancer SW1116 cell lines . Fumigaclavine C, an ergot alkaloid, inhibits LPS-induced NO production in RAW 264.7 cells .…”