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| Content Provider | PubMed Central |
|---|---|
| Author | Sarno, Renee Ha, Hongphuc Natalia, Weinsetel Tolmasky, Marcelo E. |
| Copyright Year | 2003 |
| Abstract | Amikacin has been very useful in the treatment of infections caused by multiresistant bacteria because it is refractory to the actions of most modifying enzymes. However, the spread of AAC(6′)-I-type acetyltransferases, enzymes capable of catalyzing inactivation of amikacin, has rendered this antibiotic all but useless in some parts of the world. The aminoglycoside 6′-N-acetyltransferase type Ib, which is coded for by the aac(6′)-Ib gene, mediates resistance to amikacin and other aminoglycosides. RNase H mapping and computer prediction of the secondary structure led to the identification of five regions accessible for interaction with antisense oligodeoxynucleotides in the aac(6′)-Ib mRNA. Oligodeoxynucleotides targeting these regions could bind to native mRNA with different efficiencies and mediated RNase H digestion. Selected oligodeoxynucleotides inhibited AAC(6′)-Ib synthesis in cell-free coupled transcription-translation assays. After their introduction into an Escherichia coli strain harboring aac(6′)-Ib by electroporation, some of these oligodeoxynucleotides decreased the level of resistance to amikacin. Our results indicate that use of antisense compounds could be a viable strategy to preserve the efficacies of existing antibiotics to which bacteria are becoming increasingly resistant. |
| Related Links | http://dx.doi.org/10.1128/AAC.47.10.3296-3304.2003 |
| Starting Page | 3296 |
| File Format | |
| ISSN | 10986596 |
| e-ISSN | 10986596 |
| Journal | Antimicrobial Agents and Chemotherapy |
| Issue Number | 10 |
| Volume Number | 47 |
| Language | English |
| Publisher | American Society for Microbiology |
| Publisher Date | 2003-10-01 |
| Access Restriction | Open |
| Rights Holder | American Society for Microbiology |
| Subject Keyword | Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Infectious Diseases Pharmacology Pharmacology (medical) |
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