Genomewide Screening for Novel Genetic Variations Associated with Ciprofloxacin Resistance in
Bacillus anthracis
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Published:2010-07
Issue:7
Volume:54
Page:2787-2792
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ISSN:0066-4804
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Container-title:Antimicrobial Agents and Chemotherapy
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language:en
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Short-container-title:Antimicrob Agents Chemother
Author:
Serizawa Masakuni1, Sekizuka Tsuyoshi1, Okutani Akiko2, Banno Satomi1, Sata Tetsutaro3, Inoue Satoshi2, Kuroda Makoto1
Affiliation:
1. Laboratory of Bacterial Genomics, Pathogen Genomics Center 2. Departments of Veterinary Science 3. Pathology, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan
Abstract
ABSTRACT
Fluoroquinolone (FQ) resistance of
Bacillus anthracis
is a serious concern in the fields of biodefense and bioterrorism since FQs are very effective antibiotics and are recommended as first-line treatment against this lethal bacterium. In this study, we obtained 2 strains of
B. anthracis
showing resistance or intermediate resistance to ciprofloxacin (CIP) by a stepwise selection procedure with increasing CIP concentrations. Fifteen genetic variations were identified between the parental and CIP-resistant strains by next-generation sequencing. Nonsynonymous mutations in the quinolone resistance-determining region (QRDR) of type II DNA topoisomerase were identified in the resistant strain but not in the intermediate-resistant strain. The GBAA0834 (TetR-type transcriptional regulator) locus was also revealed to be a novel “mutation hot spot” that leads to the increased expression of multidrug efflux systems for CIP resistance. As an initial step of CIP resistance in
B. anthracis
, such disruptive mutations of GBAA0834 appear to be more easily acquired than those in an essential gene, such as that encoding type II DNA topoisomerase. Such an intermediate-resistant phenotype could increase a cell population under CIP-selective pressure and might promote the emergence of highly resistant isolates. Our findings reveal, in addition to QRDR, crucial genetic targets for the investigation of intermediate resistance of
B. anthracis
to FQs.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Pharmacology (medical),Pharmacology
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