Issue 6, 2005

Bacterial death comes full circle: targeting plasmid replication in drug-resistant bacteria

Abstract

It is now common for bacterial infections to resist the preferred antibiotic treatment. In particular, hospital-acquired infections that are refractory to multiple antibiotics and ultimately result in death of the patient are prevalent. Many of the bacteria causing these infections have become resistant to antibiotics through the process of lateral gene transfer, with the newly acquired genes encoding a variety of resistance-mediating proteins. These foreign genes often enter the bacteria on plasmids, which are small, circular, extrachromosomal pieces of DNA. This plasmid-encoded resistance has been observed for virtually all classes of antibiotics and in a wide variety of Gram-positive and Gram-negative organisms; many antibiotics are no longer effective due to such plasmid-encoded resistance. The systematic removal of these resistance-mediating plasmids from the bacteria would re-sensitize bacteria to standard antibiotics. As such, plasmids offer novel targets that have heretofore been unexploited clinically. This Perspective details the role of plasmids in multi-drug resistant bacteria, the mechanisms used by plasmids to control their replication, and the potential for small molecules to disrupt plasmid replication and re-sensitize bacteria to antibiotics. An emphasis is placed on plasmid replication that is mediated by small counter-transcript RNAs, and the “plasmid addiction” systems that employ toxins and antitoxins.

Graphical abstract: Bacterial death comes full circle: targeting plasmid replication in drug-resistant bacteria

Article information

Article type
Perspective
Submitted
07 Jan 2005
Accepted
19 Jan 2005
First published
15 Feb 2005

Org. Biomol. Chem., 2005,3, 959-966

Bacterial death comes full circle: targeting plasmid replication in drug-resistant bacteria

J. C. B. DeNap and P. J. Hergenrother, Org. Biomol. Chem., 2005, 3, 959 DOI: 10.1039/B500182J

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