Regulation of mprF by antisense RNA restores daptomycin susceptibility to daptomycin-resistant isolates of Staphylococcus aureus.
Mutations in mprF have been shown to result in reduced susceptibility to daptomycin and other cationic antibacterials. An mprF antisense-inducible plasmid was constructed and used to demonstrate that depletion of mprF can reestablish susceptibility to daptomycin. Inducing antisense to mprF also resulted in increased susceptibility to vancomycin and gentamicin but, paradoxically, decreased susceptibility to oxacillin. These results suggest that mprF mutations that reduce susceptibility to cationic antibacterials result in a gain-of-function phenotype.
Cubist Pharmceuticals, Lexington, MA 02421, USA. aileen.rubio@cubist.com
Aileen
A
Rubio
Mary
M
Conrad
Robert J
RJ
Haselbeck
Kedar
K
G C
Vickie
V
Brown-Driver
John
J
Finn
Jared A
JA
Silverman
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics; D015152:Blotting, Northern; D017576:Daptomycin / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D005839:Gentamicins / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D016372:RNA, Antisense / Q000235:genetics*; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000235:genetics*; D014640:Vancomycin / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D005839:Gentamicins; D016372:RNA, Antisense; D014640:Vancomycin; D017576:Daptomycin