Bacterial Plasmid Holds Key to Antibiotics Production

Chemists in the United Kingdom have identified a group of signaling molecules that induce antibiotic production in Streptomyces, opening the door for the development of novel drugs to replace those declining in effectiveness as pathogenic bacteria become more resistant to them.

Investigators at the University of Warwick (Coventry, UK) worked initially with the S. coelicolor A3 strain, which contains the 356-kb linear plasmid SCP1. They found that all of the genetic elements necessary for the production of the antibiotic methylenomycin (Mm) and its regulation were contained within a 22-kb gene cluster located on the plasmid.

When the plasmid was inserted into the plasmid-free S. coelicolor M512 strain, the investigators were able to isolate a family of five new 2-alkyl-4-hydroxymethylfuran-3-carboxylic acids (AHFCAs), collectively termed Mm furans (MMFs). MMFs specifically induced the production of the Mm antibiotics in S. coelicolor.

Comparative genomics analyses and searches of the natural product chemistry literature indicated that other streptomycetes might produce AHFCAs, suggesting that they could form a general class of antibiotic biosynthesis inducers in Streptomyces species. First author Dr. Christophe Corre, research fellow in chemistry at the University of Warwick, said, "Early results also suggest that this approach could switch on novel antibiotic production pathways in up to 50% of Streptomyces bacteria. With thousands of known members of the Streptomyces family that could mean that AHFCAs could unlock hundreds of new antibiotics to replenish our dwindling arsenal of effective antibiotic drugs.”

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