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
Mechanisms of Resistance

A Ser678Pro Substitution in Fks1p Confers Resistance to Echinocandin Drugs in Aspergillus fumigatus

Eleusa Maria F. Rocha, Guillermo Garcia-Effron, Steven Park, David S. Perlin
Eleusa Maria F. Rocha
Public Health Research Institute and the Department of Microbiology and Molecular Genetics, UMDNJ-New Jersey Medical School, Newark, New Jersey 07103-3535
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Guillermo Garcia-Effron
Public Health Research Institute and the Department of Microbiology and Molecular Genetics, UMDNJ-New Jersey Medical School, Newark, New Jersey 07103-3535
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Steven Park
Public Health Research Institute and the Department of Microbiology and Molecular Genetics, UMDNJ-New Jersey Medical School, Newark, New Jersey 07103-3535
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
David S. Perlin
Public Health Research Institute and the Department of Microbiology and Molecular Genetics, UMDNJ-New Jersey Medical School, Newark, New Jersey 07103-3535
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: perlinds@umdnj.edu
DOI: 10.1128/AAC.00917-07
  • Article
  • Figures & Data
  • Info & Metrics
  • PDF
Loading

Article Figures & Data

Figures

  • Tables
  • FIG. 1.
    • Open in new tab
    • Download powerpoint
    FIG. 1.

    Amino acid sequence alignment of Fks1p containing “hot-spot 1” regions from five fungal species: Saccharomyces cerevisiae (Sc), Candida glabrata (Cg), Candida albicans (Ca), Aspergillus nidulans (An), and Aspergillus fumigatus (Af). The highly conserved Ser locus is shaded.

  • FIG. 2.
    • Open in new tab
    • Download powerpoint
    FIG. 2.

    CSF-sensitive and -resistant isolates of A. fumigatus. (A) Growth of strains EMFR-S678P (mutant) and KU80Δ (wild type) on AM3 with 10.0 μg/ml of CSF plus pyrimidine. (B) Growth of EMFR-S678P/WT containing plasmid-expressed fks1(S678P) (top set). EMFR-FKS1-Restored isolates 1 to 4 with restored sensitivity to echinocandin following loss of plasmid (bottom set). Strains were grown for 72 h at 37°C on AM3 with 10.0 μg/ml of CSF.

  • FIG. 3.
    • Open in new tab
    • Download powerpoint
    FIG. 3.

    Echinocandin inhibition profiles of enriched GS complexes from the wild type (triangles), EMFR-S678P (circles), and EMFR-FKS1-Restored (squares). The enzymes were evaluated with CSF (A), ANF (B), and MCF (C). The mixed inhibition profile to CSF for GS from EMFR-S678P/WT is also shown (D). Relative GS activities shown in all panels were assessed by the incorporation of [3H]glucose into the radiolabeled product.

Tables

  • Figures
  • TABLE 1.

    Strains and plasmids used in this study

    Strain or plasmidDescriptionReference(s) or source
    Strains
        KU80Δ A. fumigatus pyrGAF::ΔKU80; wild-type strain sensitive to echinocandin drugs 4
        EMFR-S678PHomologous recombinant fks1(S678F) mutant of KU80 formed following transformation with linear pRG3-(pyr4)-AMA1-Fks1S678P cut with HpaIThis study
        EMFR-S678P/WT fks1 mutant of KU80 transformed with uncut autonomously replicating plasmid pRG3-(pyr4)-AMA1-Fks1S678P; also contains wild-type FKS1This study
        EMFR-FKS1-RestoredStrain derived from EMFR-S678P/WT after plasmid evictionThis study
    Plasmids
        pRG3-AMA1Contains A. nidulans AMA1 and pyr4 genes 1, 2, 16
        pRG3-AMA1-Fks1S678PContains A. fumigatus fks1(S678P) in pRG3-(pyr4)-AMA1This study
  • TABLE 2.

    Echinocandin inhibition of growth and GS with wild-type and mutant strains

    StrainMEC (μg/ml)aIC50 (ng/ml)b
    CSFANFMCFCSFANFMCF
    KU80Δ0.250.0150.0150.910.240.63
    EMFR-S678P>1616>16109.7029.1712.61
    EMFR-S678P/ WT>16880.12, 104.90.37, 29.890.50, 14.38
    • ↵ a Geometric means (three repetitions from separate preparations) are given.

    • ↵ b Multiple IC50 values reflect kinetic parameters for mixed wild-type and mutant enzyme populations.

PreviousNext
Back to top
Download PDF
Citation Tools
A Ser678Pro Substitution in Fks1p Confers Resistance to Echinocandin Drugs in Aspergillus fumigatus
Eleusa Maria F. Rocha, Guillermo Garcia-Effron, Steven Park, David S. Perlin
Antimicrobial Agents and Chemotherapy Oct 2007, 51 (11) 4174-4176; DOI: 10.1128/AAC.00917-07

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.
A Ser678Pro Substitution in Fks1p Confers Resistance to Echinocandin Drugs in Aspergillus fumigatus
(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
A Ser678Pro Substitution in Fks1p Confers Resistance to Echinocandin Drugs in Aspergillus fumigatus
Eleusa Maria F. Rocha, Guillermo Garcia-Effron, Steven Park, David S. Perlin
Antimicrobial Agents and Chemotherapy Oct 2007, 51 (11) 4174-4176; DOI: 10.1128/AAC.00917-07
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Top
  • Article
    • ABSTRACT
    • ACKNOWLEDGMENTS
    • FOOTNOTES
    • REFERENCES
  • Figures & Data
  • Info & Metrics
  • PDF

KEYWORDS

Amino Acid Substitution
Aspergillus fumigatus
Drug Resistance, Fungal
echinocandins
Glucosyltransferases

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