Genomewide Screening for Novel Genetic Variations Associated with Ciprofloxacin Resistance in Bacillus anthracis

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Published inAntimicrobial Agents and Chemotherapy Vol. 54; no. 7; pp. 2787 - 2792
Main Authors Serizawa, Masakuni, Sekizuka, Tsuyoshi, Okutani, Akiko, Banno, Satomi, Sata, Tetsutaro, Inoue, Satoshi, Kuroda, Makoto
Format Journal Article
LanguageEnglish
Published Washington, DC American Society for Microbiology 01.07.2010
American Society for Microbiology (ASM)
Subjects
Antibiotics. Antiinfectious agents. Antiparasitic agents
Bacillus anthracis
Bacillus anthracis - drug effects
Bacillus anthracis - genetics
Biological and medical sciences
Ciprofloxacin
Ciprofloxacin - pharmacology
Drug Resistance, Bacterial
Drug Resistance, Bacterial - genetics
Genetic Variation
Genome, Bacterial
Genome, Bacterial - genetics
Genome-Wide Association Study
Mechanisms of Resistance
Medical sciences
Molecular Sequence Data
Mutation
Pharmacology. Drug treatments
Reverse Transcriptase Polymerase Chain Reaction
Bacillus anthracis
Genetic variability
Genotype
Bacillaceae
Medical screening
Resistance
Screening
Fluoroquinolone derivatives
Bacillales
Bacteria
Antibacterial agent
Ciprofloxacin
Quinolone derivatives
Polymorphism
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Abstract Classifications Services AAC Citing Articles Google Scholar PubMed Related Content Social Bookmarking CiteULike Delicious Digg Facebook Google+ Mendeley Reddit StumbleUpon Twitter current issue AAC About AAC Subscribers Authors Reviewers Advertisers Inquiries from the Press Permissions & Commercial Reprints ASM Journals Public Access Policy AAC RSS Feeds 1752 N Street N.W. • Washington DC 20036 202.737.3600 • 202.942.9355 fax • journals@asmusa.org Print ISSN: 0066-4804 Online ISSN: 1098-6596 Copyright © 2014 by the American Society for Microbiology.   For an alternate route to AAC .asm.org, visit: AAC       
AbstractList 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.
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.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.
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.
Classifications Services AAC Citing Articles Google Scholar PubMed Related Content Social Bookmarking CiteULike Delicious Digg Facebook Google+ Mendeley Reddit StumbleUpon Twitter current issue AAC About AAC Subscribers Authors Reviewers Advertisers Inquiries from the Press Permissions & Commercial Reprints ASM Journals Public Access Policy AAC RSS Feeds 1752 N Street N.W. • Washington DC 20036 202.737.3600 • 202.942.9355 fax • journals@asmusa.org Print ISSN: 0066-4804 Online ISSN: 1098-6596 Copyright © 2014 by the American Society for Microbiology.   For an alternate route to AAC .asm.org, visit: AAC       
Author Makoto Kuroda
Satoshi Inoue
Satomi Banno
Tsuyoshi Sekizuka
Akiko Okutani
Tetsutaro Sata
Masakuni Serizawa
AuthorAffiliation Laboratory of Bacterial Genomics, Pathogen Genomics Center, 1 Departments of Veterinary Science, 2 Pathology, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan 3
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Issue 7
Keywords Bacillus anthracis
Genetic variability
Genotype
Bacillaceae
Medical screening
Resistance
Screening
Fluoroquinolone derivatives
Bacillales
Bacteria
Antibacterial agent
Ciprofloxacin
Quinolone derivatives
Polymorphism
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Fluoroquinolone (FQ) resistance of Bacillus anthracis is a serious concern in the fields of biodefense and bioterrorism since FQs are very effective...
Fluoroquinolone (FQ) resistance of Bacillus anthracis is a serious concern in the fields of biodefense and bioterrorism since FQs are very effective...
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StartPage 2787
SubjectTerms Antibiotics. Antiinfectious agents. Antiparasitic agents
Bacillus anthracis
Bacillus anthracis - drug effects
Bacillus anthracis - genetics
Biological and medical sciences
Ciprofloxacin
Ciprofloxacin - pharmacology
Drug Resistance, Bacterial
Drug Resistance, Bacterial - genetics
Genetic Variation
Genome, Bacterial
Genome, Bacterial - genetics
Genome-Wide Association Study
Mechanisms of Resistance
Medical sciences
Molecular Sequence Data
Mutation
Pharmacology. Drug treatments
Reverse Transcriptase Polymerase Chain Reaction
Title Genomewide Screening for Novel Genetic Variations Associated with Ciprofloxacin Resistance in Bacillus anthracis
URI http://aac.asm.org/content/54/7/2787.abstract
https://www.ncbi.nlm.nih.gov/pubmed/20385868
https://journals.asm.org/doi/10.1128/AAC.01405-09
https://www.proquest.com/docview/733350858
https://www.proquest.com/docview/746161822
https://pubmed.ncbi.nlm.nih.gov/PMC2897295
Volume 54
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