期刊
RNA BIOLOGY
卷 6, 期 2, 页码 187-194出版社
TAYLOR & FRANCIS INC
DOI: 10.4161/rna.6.2.7727
关键词
antibiotic; antimetabolite; aptamer; Bacillus subtilis; flavin mononucleotide; riboflavin; Streptomyces davawensis
资金
- NIH [U54AI57158, R33 DK07027, GM 068819]
- National Institute of General Medical Sciences [T32GM007223]
- Howard Hughes Medical Institute
Riboswitches in messenger RNAs carry receptor domains called aptamers that can bind to metabolites and control expression of associated genes. The Gram-positive bacterium Bacillus subtilis has two representatives of a class of riboswitches that bind flavin mononucleotide (FMN). These riboswitches control genes responsible for the biosynthesis and transport of riboflavin, a precursor of FMN. We found that roseoflavin, a chemical analog of FMN and riboflavin that has antimicrobial activity, can directly bind to FMN riboswitch aptamers and downregulate the expression of an FMN riboswitch-LacZ reporter gene in B. subtilis. A role for the riboswitch in the antimicrobial mechanism of roseoflavin is supported by our observation that some previously identified roseoflavin-resistant bacteria have mutations within an FMN aptamer. Riboswitch mutations in these resistant bacteria disrupt ligand binding and derepress reporter gene expression in the presence of either riboflavin or roseoflavin. If FMN riboswitches are a major target for roseoflavin antimicrobial action, then future efforts to develop compounds that trigger FMN riboswitch function could lead to the identification of new antimicrobial drugs.
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