Removing Plasmids Eliminates Antibiotic Resistance

Researchers have treated antibiotic-resistant bacteria with the drug apramycin to inhibit and ultimately remove the plasmids responsible for acquisition of the antibiotic resistance.

Plasmids are bits of extra-chromosomal DNA that are exchanged when bacteria interact. Among the genes carried on plasmids are those responsible for antibiotic resistance. Investigators at the University of Illinois (Urbana-Champaign, USA) selected apramycin, an aminoglycoside antibiotic with bactericidal activity against most Gram-negative bacteria, after testing numerous other potentially useful molecules. They reported in the November 5, 2004, online edition of the Journal of the American Chemical Society that the positively charged apramycin bound to negatively charged plasmid-encoded RNA. This binding inhibited the activity of proteins that trigger plasmid reproduction.

Apramycin was used to treat bacterial cultures that were grown for 250 generations. By the end of this period, plasmids had been eliminated, and the culture had lost its antibiotic resistance.

"This is the first demonstration of a mechanistic-based approach to systematically eliminate the plasmids,” said senior author Dr. Paul J. Hergenrother, professor of chemistry at the University of Illinois. "Standard antibiotics target the cell wall, but as resistance to antibiotics emerges, there needs to be other targets. We validated that plasmids are a new target for antibiotics.”




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