Antibacterial Activity and AbFtsZ Binding Properties of Fungal Metabolites Isolated from Mexican Mangroves

Antimicrobial resistance is emerging as a global health challenge that requires immediate and concerted attention. Accordingly, the WHO has issued alerts urging to continue developing antibiotics with novel mechanisms of action toward clinically important pathogens, including Acinetobacter baumannii. In this context, fungi have played a crucial role in the discovery and development of antibiotics. Therefore, in this work, three fungal strains were prioritized based on their metabolic profiles and antibacterial activity against a pan-resistant isolate of A. baumannii, to identify potential antibiotic molecules. Chemical investigation of the selected fungi (mangrove endophytes) led to the isolation of asperazine (1), aurasperone B (2), aurasperone F (3), TMC-256A1 (4), fonsecin B (5), dianhydroaurasperone C (6), aurasperone A (7), pyrophen (8), and penicillide (9). Moreover, an in vitro assay to detect ligands of the filamentous temperature-sensitive mutant Z enzyme of A. baumannii (AbFtsZ), a GTPase that plays a central role in bacterial division, was developed to correlate the antibacterial properties of the isolated molecules to a mechanism of action. Compounds 1–4 and 9 inhibited the growth of A. baumannii. Interestingly, compounds 2, 3, and 5–9 interacted with AbFtsZ1-412, increasing its GTPase activity. Conversely, compound 4 exhibited an outstanding ability to act as an inhibitor of both the enzymatic activity and the growth of the strain under study.