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The UvrA ‐like protein Ecm16 requires ATPase activity to render resistance against echinomycin
Author(s) -
Erlandson Amanda,
Gade Priyanka,
Menikpurage Inoka P.,
Kim ChuYoung,
Mera Paola E.
Publication year - 2022
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/mmi.14918
Subject(s) - biology , dna , nucleotide excision repair , bacteria , nucleotide , escherichia coli , atpase , biochemistry , dna repair , genetics , gene , enzyme
Bacteria use various strategies to become antibiotic resistant. The molecular details of these strategies are not fully understood. We can increase our understanding by investigating the same strategies found in antibiotic‐producing bacteria. In this work, we characterize the self‐resistance protein Ecm16 encoded by echinomycin‐producing bacteria. Ecm16 is a structural homolog of the nucleotide excision repair protein UvrA. Expression of ecm16 in the heterologous system Escherichia coli was sufficient to render resistance against echinomycin. Ecm16 binds DNA (double‐stranded and single‐stranded) using a nucleotide‐independent binding mode. Ecm16’s binding affinity for DNA increased by 1.7‐fold when the DNA is intercalated with echinomycin. Ecm16 can render resistance against echinomycin toxicity independently of the nucleotide excision repair system. Similar to UvrA, Ecm16 has ATPase activity, and this activity is essential for Ecm16’s ability to render echinomycin resistance. Notably, UvrA and Ecm16 were unable to complement each other's function. Together, our findings identify new mechanistic details of how a refurbished DNA repair protein Ecm16 can specifically render resistance to the DNA intercalator echinomycin.