Skip to main content
  • ASM
    • Antimicrobial Agents and Chemotherapy
    • Applied and Environmental Microbiology
    • Clinical Microbiology Reviews
    • Clinical and Vaccine Immunology
    • EcoSal Plus
    • Eukaryotic Cell
    • Infection and Immunity
    • Journal of Bacteriology
    • Journal of Clinical Microbiology
    • Journal of Microbiology & Biology Education
    • Journal of Virology
    • mBio
    • Microbiology and Molecular Biology Reviews
    • Microbiology Resource Announcements
    • Microbiology Spectrum
    • Molecular and Cellular Biology
    • mSphere
    • mSystems
  • Log in
  • My alerts
  • My Cart

Main menu

  • Home
  • Articles
    • Current Issue
    • Accepted Manuscripts
    • COVID-19 Special Collection
    • Archive
    • Minireviews
  • For Authors
    • Submit a Manuscript
    • Scope
    • Editorial Policy
    • Submission, Review, & Publication Processes
    • Organization and Format
    • Errata, Author Corrections, Retractions
    • Illustrations and Tables
    • Nomenclature
    • Abbreviations and Conventions
    • Publication Fees
    • Ethics Resources and Policies
  • About the Journal
    • About AAC
    • Editor in Chief
    • Editorial Board
    • For Reviewers
    • For the Media
    • For Librarians
    • For Advertisers
    • Alerts
    • AAC Podcast
    • RSS
    • FAQ
  • Subscribe
    • Members
    • Institutions
  • ASM
    • Antimicrobial Agents and Chemotherapy
    • Applied and Environmental Microbiology
    • Clinical Microbiology Reviews
    • Clinical and Vaccine Immunology
    • EcoSal Plus
    • Eukaryotic Cell
    • Infection and Immunity
    • Journal of Bacteriology
    • Journal of Clinical Microbiology
    • Journal of Microbiology & Biology Education
    • Journal of Virology
    • mBio
    • Microbiology and Molecular Biology Reviews
    • Microbiology Resource Announcements
    • Microbiology Spectrum
    • Molecular and Cellular Biology
    • mSphere
    • mSystems

User menu

  • Log in
  • My alerts
  • My Cart

Search

  • Advanced search
Antimicrobial Agents and Chemotherapy
publisher-logosite-logo

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Accepted Manuscripts
    • COVID-19 Special Collection
    • Archive
    • Minireviews
  • For Authors
    • Submit a Manuscript
    • Scope
    • Editorial Policy
    • Submission, Review, & Publication Processes
    • Organization and Format
    • Errata, Author Corrections, Retractions
    • Illustrations and Tables
    • Nomenclature
    • Abbreviations and Conventions
    • Publication Fees
    • Ethics Resources and Policies
  • About the Journal
    • About AAC
    • Editor in Chief
    • Editorial Board
    • For Reviewers
    • For the Media
    • For Librarians
    • For Advertisers
    • Alerts
    • AAC Podcast
    • RSS
    • FAQ
  • Subscribe
    • Members
    • Institutions
Letter to the Editor

Multiple Resistance Mechanisms in Fluoroquinolone-Resistant Salmonella Isolates from Germany

Beatriz Guerra, Burkhard Malorny, Andreas Schroeter, Reiner Helmuth
Beatriz Guerra
Federal Institute for Risk Assessment (BfR) National Salmonella Reference Laboratory Diedersdorfer Weg 1 D-12277 Berlin, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Burkhard Malorny
Federal Institute for Risk Assessment (BfR) National Salmonella Reference Laboratory Diedersdorfer Weg 1 D-12277 Berlin, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Andreas Schroeter
Federal Institute for Risk Assessment (BfR) National Salmonella Reference Laboratory Diedersdorfer Weg 1 D-12277 Berlin, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Reiner Helmuth
Federal Institute for Risk Assessment (BfR) National Salmonella Reference Laboratory Diedersdorfer Weg 1 D-12277 Berlin, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: r.helmuth@bfr.bund.de
DOI: 10.1128/AAC.47.6.2059.2003
  • Article
  • Info & Metrics
  • PDF
Loading

During the early 1990s, a clone of multiresistant Salmonella enterica serovar Typhimurium O5 negative (var. Copenhagen) of phage type DT204c predominated in Germany and neighboring countries within the calf-fattening industry. In addition to being resistant to ampicillin, kanamycin, tetracycline, chloramphenicol, and trimethoprim, these isolates were highly resistant to nalidixic acid (MIC > 128 μg/ml) and ciprofloxacin (MIC = 32 μg/ml) (4). Heisig et al. (3) showed that the clone had spread among humans and animals in Germany, and complementation experiments suggested that mutations in gyrA and gyrB were responsible for the high level of fluoroquinolone resistance. DNA sequencing of gyrA revealed two amino acid substitutions (Ser83→Ala and Asp87→Asn) (3).

Our recent molecular characterization of fluoroquinolone-resistance mechanisms in contemporary and old Salmonella strains showed that two such German isolates of bovine origin carried these gyrA mutations and a novel gyrB mutation together with a novel parC mutation in each strain. Both isolates (NRL608/93 and NRL154/94) were received at the German National Salmonella Reference Laboratory in the early 1990s, and the following MICs of fluoroquinolones were observed by the standard NCCLS broth dilution method (7): ciprofloxacin, 32 μg/ml; enrofloxacin, >128 μg/ml; levofloxacin, 16 and 8 μg/ml; moxifloxacin, 32 μg/ml; and ofloxacin, >128 μg/ml. In order to investigate the underlying resistance mechanisms, the quinolone resistance-determining regions (QRDRs) were amplified by using specific primers for gyrA and parC (6) and gyrB (F, ACTGGCGGACTGTCAGGAAC; B, TCTGACGATAGAAGAAGGTCAAC). Sequencing was carried out as described in reference 6. The most relevant findings were as follows. (i) Sequence analysis of the QRDR of the gyrA gene detected the mutations Ser83→Ala (TCC→GCC) and Asp87→Asn (GAC→AAC). (ii) Sequence analysis of the QRDR of gyrB showed in both isolates the novel mutation Ser464→Phe (TCC→TTC). This change may alter the hydrophobicity of the protein. In Salmonella, the substitution Ser464→Tyr in gyrB, which does not affect the local charge or hydrophobicity of the protein, had been described most frequently (2, 8). (iii) Sequence analysis of the QRDR of parC showed in both isolates the mutation Ser80→Ile (AGC→ATC). This parC substitution has frequently been described for high-level resistance to fluoroquinolones in Escherichia coli in combination with gyrA double mutations (8). Recently, Baucheron et al. (1) described this mutation for Belgian Salmonella isolates. (iv) Phenotypic analysis of the tolerance to the organic solvent cyclohexane (5) showed that both isolates were resistant. This cyclohexane resistance suggests the possession of broad-spectrum efflux pumps implicated in the high resistance to the hydrophilic fluoroquinolones as well. Although the contributions of the various genetic mechanisms described above to the fluoroquinolone resistance phenotype were not elucidated in our study, genetic work in other species (8) suggests their relevance.

The description of this particular clone is of special importance, since it was part of a wide animal outbreak and sporadic human infections (4). The isolation of multiresistant strains from cattle with at least four different genetic backgrounds (double mutation in gyrA, single mutation in gyrB, single mutation in parC, and the presumable presence of efflux pumps) implicated in fluoroquinolone resistance should be a cause of concern and be prevented in the future by decreasing selective pressure.

ACKNOWLEDGMENTS

We thank E. Junker, M. Jaber, and B. Hoog for their helpful assistance.  This work was supported by the grants of the Federal Institute for Risk Assessment, BfR (formerly BgVV, Ref. F501-28/1322-136).

  • Copyright © 2003 American Society for Microbiology

REFERENCES

  1. 1.↵
    Baucheron, S., H. Imberechts, E. Chaslus-Dancla, and A. Cloeckaert. 2002. The AcrB multidrug transporter plays a major role in high level fluoroquinolone resistance in Salmonella enterica serovar Typhimurium phage type DT204. Microb. Drug. Res.8:281-289.
    OpenUrlCrossRef
  2. 2.↵
    Cloeckaert, A., and E. Chaslus-Dancla. 2001. Mechanisms of quinolone resistance in Salmonella. Vet. Res.32:291-300.
    OpenUrlCrossRefPubMedWeb of Science
  3. 3.↵
    Heisig, P., B. Kratz, E. Halle, Y. Graser, M. Altwegg, W. Rabsch, and J. Faber. 1995. Identification of DNA gyrase A mutations in ciprofloxacin-resistant isolates of Salmonella typhimurium from men and cattle in Germany. Microb. Drug. Res.1:211-218.
    OpenUrl
  4. 4.↵
    Helmuth, R. 2000. Antibiotic resistance in Salmonella, p. 89-106. In C. Wray and A. Wray (ed.), Salmonella in domestic animals. CABI Publishing, Oxon, United Kingdom.
  5. 5.↵
    Liebana, E., C. Clouting, C. A. Cassar, L. P. Randall, R. A. Walker, E. John Threlfall, F. A. Clifton-Hadley, A. M. Ridley, and R. H. Davies. 2002. Comparison of gyrA mutations, cyclohexane resistance, and the presence of class I integrons in Salmonella enterica from farm animals in England and Wales. J. Clin. Microbiol.40:1481-1486.
    OpenUrlAbstract/FREE Full Text
  6. 6.↵
    Malorny, B., A. Schroeter, B. Guerra, and R. Helmuth. Incidence of quinolone resistance in veterinary Salmonella strains isolated in Germany between 1998 and 2001. Vet. Rec., in press.
  7. 7.↵
    National Committee for Clinical Laboratory Standards. 2000. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically. Approved standard M7-A5. National Committee for Clinical Laboratory Standards, Wayne, Pa.
  8. 8.↵
    Piddock, L. J. V. 2002. Fluoroquinolone resistance in Salmonella serovars isolated from human and food animals. FEMS Microbiol. Rev.26:3-16.
    OpenUrlCrossRefPubMedWeb of Science
PreviousNext
Back to top
Download PDF
Citation Tools
Multiple Resistance Mechanisms in Fluoroquinolone-Resistant Salmonella Isolates from Germany
Beatriz Guerra, Burkhard Malorny, Andreas Schroeter, Reiner Helmuth
Antimicrobial Agents and Chemotherapy Jun 2003, 47 (6) 2059; DOI: 10.1128/AAC.47.6.2059.2003

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Print

Alerts
Sign In to Email Alerts with your Email Address
Email

Thank you for sharing this Antimicrobial Agents and Chemotherapy article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
Multiple Resistance Mechanisms in Fluoroquinolone-Resistant Salmonella Isolates from Germany
(Your Name) has forwarded a page to you from Antimicrobial Agents and Chemotherapy
(Your Name) thought you would be interested in this article in Antimicrobial Agents and Chemotherapy.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Multiple Resistance Mechanisms in Fluoroquinolone-Resistant Salmonella Isolates from Germany
Beatriz Guerra, Burkhard Malorny, Andreas Schroeter, Reiner Helmuth
Antimicrobial Agents and Chemotherapy Jun 2003, 47 (6) 2059; DOI: 10.1128/AAC.47.6.2059.2003
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Top
  • Article
    • ACKNOWLEDGMENTS
    • REFERENCES
  • Info & Metrics
  • PDF

KEYWORDS

anti-infective agents
Salmonella Infections, Animal
Salmonella Typhimurium

Related Articles

Cited By...

About

  • About AAC
  • Editor in Chief
  • Editorial Board
  • Policies
  • For Reviewers
  • For the Media
  • For Librarians
  • For Advertisers
  • Alerts
  • AAC Podcast
  • RSS
  • FAQ
  • Permissions
  • Journal Announcements

Authors

  • ASM Author Center
  • Submit a Manuscript
  • Article Types
  • Ethics
  • Contact Us

Follow #AACJournal

@ASMicrobiology

       

ASM Journals

ASM journals are the most prominent publications in the field, delivering up-to-date and authoritative coverage of both basic and clinical microbiology.

About ASM | Contact Us | Press Room

 

ASM is a member of

Scientific Society Publisher Alliance

 

American Society for Microbiology
1752 N St. NW
Washington, DC 20036
Phone: (202) 737-3600

Copyright © 2021 American Society for Microbiology | Privacy Policy | Website feedback

Print ISSN: 0066-4804; Online ISSN: 1098-6596