Disrupting antibiotic resistance propagation by inhibiting the conjugative DNA relaxase.

Disrupting antibiotic resistance propagation by inhibiting the conjugative DNA relaxase. Research Abstract Details 

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Disrupting antibiotic resistance propagation by inhibiting the conjugative DNA relaxase. Abstract Text:

Scott A Lujan,Laura M Guogas,Heather Ragonese,Steven W Matson,Matthew R Redinbo,

Conjugative transfer of plasmid DNA via close cell-cell junctions is the main route by which antibiotic resistance genes spread between bacterial strains. Relaxases are essential for conjugative transfer and act by cleaving DNA strands and forming covalent phosphotyrosine linkages. Based on data indicating that multityrosine relaxase enzymes can accommodate two phosphotyrosine intermediates within their divalent metal-containing active sites, we hypothesized that bisphosphonates would inhibit relaxase activity and conjugative DNA transfer. We identified bisphosphonates that are nanomolar inhibitors of the F plasmid conjugative relaxase in vitro. Furthermore, we used cell-based assays to demonstrate that these compounds are highly effective at preventing DNA transfer and at selectively killing cells harboring conjugative plasmids. Two potent inhibitors, clodronate and etidronate, are already clinically approved to treat bone loss. Thus, the inhibition of conjugative relaxases is a potentially novel antimicrobial approach, one that selectively targets bacteria capable of transferring antibiotic resistance and generating multidrug resistant strains.

Disrupting antibiotic resistance propagation by inhibiting the conjugative DNA relaxase. Publishing Authors By Initials

SA Lujan,LM Guogas,H Ragonese,SW Matson,MR Redinbo,

For similar biochemical phenomena, metabolism, and nutrition: biochemical phenomena: molecular structure: molecular conformation: protein conformation: protein structure, tertiary research abstracts see: biochemical phenomena, metabolism, and nutrition: biochemical phenomena: molecular structure: molecular conformation: protein conformation: protein structure, tertiary research

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MEDLINE DATE:

Disrupting antibiotic resistance propagation by inhibiting the conjugative DNA relaxase. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Proceedings of the National Academy of Sciences of

VOLUME: 104

Page Numbers: 12282-7

Journal Abbreviation: Proc. Natl. Acad. Sci. U.S.A.

ISSN: 0027-8424

DAY: 13

MONTH: 07

YEAR: 2007

Disrupting antibiotic resistance propagation by inhibiting the conjugative DNA relaxase. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 7505876

Disrupting antibiotic resistance propagation by inhibiting the conjugative DNA relaxase. Keywords Mesh Terms:

KEYWORDS: Protein Structure, Tertiary

MESH TERMS: drug effects

Chemical & Substance for Abstract: Disrupting antibiotic resistance propagation by inhibiting the conjugative DNA relaxase. Information

Substance Name: DNA relaxase

Registry Number: EC 2.7.7.-

Grant and Affiliation Information for Disrupting antibiotic resistance propagation by inhibiting the conjugative DNA relaxase.

AFFILIATION: Department of Chemistry, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599-3290, USA.

Country: United States

AGENCY: United States NIGMS

GRANT: GM61020

ACRONYM: GM

MEDLINETA: Proc Natl Acad Sci U S A

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