biostudies-literatureSychantha DGouvernement du Canada | Canadian Institutes of Health ResearchGouvernement du Canada | Canadian Institutes of Health Research (Instituts de Recherche en Santé du Canada)4036https://www.ebi.ac.uk/biostudies/studies/S-EPMC11091072biostudies-literatureUnknown15(1)Microbial Ni²⁺ homeostasis underpins the virulence of several clinical pathogens. Ni²⁺ is an essential cofactor in urease and [NiFe]-hydrogenases involved in colonization and persistence. Many microbes produce metallophores to sequester metals necessary for their metabolism and starve competing neighboring organisms. The fungal metallophore aspergillomarasmine A (AMA) shows narrow specificity for Zn²⁺, Ni²⁺, and Co²⁺. Here, we show that this specificity allows AMA to block the uptake of Ni²⁺ and attenuate bacterial Ni-dependent enzymes, offering a potential strategy for reducing virulence. Bacterial exposure to AMA perturbs H₂ metabolism, ureolysis, struvite crystallization, and biofilm formation and shows efficacNature communicationsTargeting bacterial nickel transport with aspergillomarasmine A suppresses virulence-associated Ni-dependent enzymes.PMC11091072FRN-I48463Prehna GSychantha DChen XKoteva KWright GDfalseTargeting bacterial nickel transport with aspergillomarasmine A suppresses virulence-associated Ni-dependent enzymes.Microbial Ni²⁺ homeostasis underpins the virulence of several clinical pathogens. Ni²⁺ is an essential cofactor in urease and [NiFe]-hydrogenases involved in colonization and persistence. Many microbes produce metallophores to sequester metals necessary for their metabolism and starve competing neighboring organisms. The fungal metallophore aspergillomarasmine A (AMA) shows narrow specificity for Zn²⁺, Ni²⁺, and Co²⁺. Here, we show that this specificity allows AMA to block the uptake of Ni²⁺ and attenuate bacterial Ni-dependent enzymes, offering a potential strategy for reducing virulence. Bacterial exposure to AMA perturbs H₂ metabolism, ureolysis, struvite crystallization, and biofilm formation and shows efficac2024-01-01T00:00:00Z2024 May2026-04-08T19:49:16.784Z2026-04-08T14:31:16.17ZS-EPMC110910723874075010.1038/s41467-024-48232-1