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A novel approach to combating antibi...

Cirz, Ryan T.

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A novel approach to combating antibiotic resistance: Inhibition of mutation as a therapeutic strategy.

Record Type:	Language materials, printed : Monograph/item
Title/Author:	A novel approach to combating antibiotic resistance: Inhibition of mutation as a therapeutic strategy./
Author:	Cirz, Ryan T.
Description:	212 p.
Notes:	Adviser: Floyd Romesberg.
Contained By:	Dissertation Abstracts International68-03B.
Subject:	Biology, Microbiology. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3256519

A novel approach to combating antibiotic resistance: Inhibition of mutation as a therapeutic strategy.
Cirz, Ryan T.

A novel approach to combating antibiotic resistance: Inhibition of mutation as a therapeutic strategy. - 212 p.

Adviser: Floyd Romesberg.

Thesis (Ph.D.)--The Scripps Research Institute, 2007.

The continual emergence of antibiotic-resistant pathogens represents a major threat to human health. In fact, bacteria now exist that are essentially untreatable by all of our conventional drugs. This alarming trend is due to the fact that bacteria are constantly evolving drug resistance through the generation of diversity (by mutation) and through natural selection of strains with increased drug resistance. Mutation has long been thought to be a passive process, however observations over the past several decades have fueled a new perspective on the process of mutagenesis: that under some conditions it is an active, regulated process that requires specific enzymes to function efficiently. Some of the conditions that have been shown to induce mutagenesis include DNA damage, extended periods of starvation, and the stress associated with antibiotic treatment.Subjects--Topical Terms:

1017734
Biology, Microbiology.

A novel approach to combating antibiotic resistance: Inhibition of mutation as a therapeutic strategy.
LDR:02797nam 2200277 a 45 001 967735
005 20110915
008 110915s2007 eng d
035 $a (UMI)AAI3256519
035 $a AAI3256519
040 $a UMI $c UMI
100 1 $a Cirz, Ryan T. $3 1291603
245 1 2 $a A novel approach to combating antibiotic resistance: Inhibition of mutation as a therapeutic strategy.
300 $a 212 p.
500 $a Adviser: Floyd Romesberg.
500 $a Source: Dissertation Abstracts International, Volume: 68-03, Section: B, page: 1421.
502 $a Thesis (Ph.D.)--The Scripps Research Institute, 2007.
520 $a The continual emergence of antibiotic-resistant pathogens represents a major threat to human health. In fact, bacteria now exist that are essentially untreatable by all of our conventional drugs. This alarming trend is due to the fact that bacteria are constantly evolving drug resistance through the generation of diversity (by mutation) and through natural selection of strains with increased drug resistance. Mutation has long been thought to be a passive process, however observations over the past several decades have fueled a new perspective on the process of mutagenesis: that under some conditions it is an active, regulated process that requires specific enzymes to function efficiently. Some of the conditions that have been shown to induce mutagenesis include DNA damage, extended periods of starvation, and the stress associated with antibiotic treatment.
520 $a Our work seeks to investigate the possibility of intervening in the active mutation process as a means to prevent or significantly delay the development of antibiotic resistance. We investigate the mechanism of ciprofloxacin-induced mutagenesis in the bacterium Escherichia coli and define which proteins are required for induced mutation in vitro and in a mouse infection model. In addition, we define the cellular response to ciprofloxacin and the induced mutation pathways of the important human pathogens, Pseudomonas aeruginosa and Staphylococcus aureus. We then characterize a mutant of Pseudomonas aeruginosa that has evolved resistance to ciprofloxacin by a non-canonical mechanism, by slowing its growth rate. Finally, we develop a high-throughput assay to identify potential inhibitors of the induced mutation process. In total, we demonstrate that the inhibition of mutation is a viable therapeutic strategy; this may have tremendous public health benefits and would represent a completely new frontier in medicine.
590 $a School code: 1179.
650 4 $a Biology, Microbiology. $3 1017734
650 4 $a Biology, Molecular. $3 1017719
690 $a 0307
690 $a 0410
710 2 0 $a The Scripps Research Institute. $3 1251203
773 0 $t Dissertation Abstracts International $g 68-03B.
790 $a 1179
790 1 0 $a Romesberg, Floyd, $e advisor
791 $a Ph.D.
792 $a 2007
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3256519