For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
17
views
13
references
 Top references
cited by
31
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      4
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Emergence of Echinocandin Resistance Due to a Point Mutation in the fks1 Gene of Aspergillus fumigatus in a Patient with Chronic Pulmonary Aspergillosis

      brief-report

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          ABSTRACT

          We have identified the first case of an fks1 hot spot 1 point mutation causing echinocandin resistance in a clinical Aspergillus fumigatus isolate recovered from a chronic pulmonary aspergillosis patient with an aspergilloma who first failed azole and polyene therapy and subsequently failed micafungin treatment.

          Related collections

          Most cited references13

          • Record: found
          • Abstract: found
          • Article: found
          Is Open Access

          Prospective Multicenter International Surveillance of Azole Resistance in Aspergillus fumigatus

          J.W.M. van der Linden, M.C. Arendrup, A. Warris … (2015)
          To investigate azole resistance in clinical Aspergillus isolates, we conducted prospective multicenter international surveillance. A total of 3,788 Aspergillus isolates were screened in 22 centers from 19 countries. Azole-resistant A. fumigatus was more frequently found (3.2% prevalence) than previously acknowledged, causing resistant invasive and noninvasive aspergillosis and severely compromising clinical use of azoles.
          Article 0 comments Cited 147 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Effect of Candida glabrata FKS1 and FKS2 mutations on echinocandin sensitivity and kinetics of 1,3-beta-D-glucan synthase: implication for the existing susceptibility breakpoint.

            Michael Cleary, Guillermo Garcia‐Manero, David Park … (2009)
            Thirteen Candida glabrata strains harboring a range of mutations in hot spot regions of FKS1 and FKS2 were studied. The mutations were linked to an echinocandin reduced susceptibility phenotype. Sequence alignments showed that 11 out of the 13 mutants harbored a mutation in FKS1 or FKS2 not previously implicated in echinocandin reduced susceptibility in C. glabrata. A detailed kinetic characterization demonstrated that amino acid substitutions in Fks1p and Fks2p reduced drug sensitivity in mutant 1,3-beta-D-glucan synthase by 2 to 3 log orders relative to that in wild-type enzyme. These mutations were also found to reduce the catalytic efficiency of the enzyme (Vmax) and to influence the relative expression of FKS genes. In view of the association of FKS mutations and reduced susceptibility of 1,3-beta-D-glucan synthase, an evaluation of the new CLSI echinocandin susceptibility breakpoint was conducted. Only 3 of 13 resistant fks mutants (23%) were considered anidulafungin or micafungin nonsusceptible (MIC > 2 microg/ml) by this criterion. In contrast, most fks mutants (92%) exceeded a MIC of >2 microg/ml with caspofungin. However, when MIC determinations were performed in the presence of 50% serum, all C. glabrata fks mutants showed MICs of > or = 2 microg/ml for the three echinocandin drugs. As has been observed with Candida albicans, the kinetic inhibition parameter 50% inhibitory concentration may be a better predictor of FKS-mediated resistance. Finally, the close association between FKS1/FKS2 hot spot mutations provides a basis for understanding echinocandin resistance in C. glabrata.
            Article 0 comments Cited 88 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Exploring azole antifungal drug resistance in Aspergillus fumigatus with special reference to resistance mechanisms.

              Anuradha Chowdhary, Cheshta Sharma, Ferry Hagen … (2014)
              Aspergillus fumigatus, a ubiquitously distributed opportunistic pathogen, is the global leading cause of aspergillosis. Azole antifungals play an important role in the management of aspergillosis. However, over a decade, azole resistance in A. fumigatus isolates has been increasingly reported with variable prevalence worldwide and it is challenging the effective management of aspergillosis. The high mortality rates observed in patients with invasive aspergillosis caused by azole-resistant A. fumigatus (ARAF) isolates pose serious challenges to the clinical microbiologist for timely identification of resistance and appropriate therapeutic interventions. The majority of ARAF isolates contain alterations in the cyp51A gene; however, there have been increasing reports on non-cyp51A mutations contributing to azole resistant phenotypes. This review highlights the emergence and various mechanisms implicated in the development of azole resistance in A. fumigatus. We further present recent developments related to the environmental route in the emergence of ARAF isolates and discuss the therapeutic options available.
              Article 0 comments Cited 62 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Journal
                Journal ID (nlm-ta): Antimicrob Agents Chemother
                Journal ID (iso-abbrev): Antimicrob. Agents Chemother
                Journal ID (hwp): aac
                Journal ID (pmc): aac
                Journal ID (publisher-id): AAC
                Title: Antimicrobial Agents and Chemotherapy
                Publisher: American Society for Microbiology (1752 N St., N.W., Washington, DC )
                ISSN (Print): 0066-4804
                ISSN (Electronic): 1098-6596
                Publication date (Electronic preprint): 18 September 2017
                Publication date (Electronic): 22 November 2017
                Publication date Collection: December 2017
                Publication date PMC-release: 22 November 2017
                Volume: 61
                Issue: 12
                Electronic Location Identifier: e01277-17
                Affiliations
                [a ]Public Health Research Institute-New Jersey Medical School-Rutgers Biomedical Health Sciences, Newark, New Jersey, USA
                [b ]Mycology Reference Centre, Manchester, University Hospital of South Manchester, Manchester, United Kingdom
                [c ]University of Manchester, Manchester, United Kingdom
                Author notes
                Address correspondence to Cristina Jiménez-Ortigosa, jimenecr@ 123456njms.rutgers.edu .

                Citation Jiménez-Ortigosa C, Moore C, Denning DW, Perlin DS. 2017. Emergence of echinocandin resistance due to a point mutation in the fks1 gene of Aspergillus fumigatus in a patient with chronic pulmonary aspergillosis. Antimicrob Agents Chemother 61:e01277-17. https://doi.org/10.1128/AAC.01277-17.

                Article
                Publisher ID: 01277-17
                DOI: 10.1128/AAC.01277-17
                PMC ID: 5700295
                PubMed ID: 28923871
                SO-VID: b9e801bd-2875-4433-94a5-faf8e13ffc4e
                Copyright © Copyright © 2017 Jiménez-Ortigosa et al.
                License:

                This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.

                History
                Date received : 21 June 2017
                Date revision requested : 30 July 2017
                Date accepted : 6 September 2017
                Page count
                Figures: 2, Tables: 3, Equations: 0, References: 18, Pages: 6, Words: 3126
                Funding
                Funded by: Astellas Pharma US (Astellas) https://doi.org/10.13039/100004324
                Award ID: 813386
                Award Recipient : David S. Perlin
                Categories
                Subject: Mechanisms of Resistance
                Custom metadata
                cover-date December 2017

                ScienceOpen disciplines: Infectious disease & Microbiology
                Keywords: aspergillus fumigatus,chronic pulmonary aspergillosis,echinocandin resistance,fks1 mutation,micafungin
                Data availability:
                ScienceOpen disciplines: Infectious disease & Microbiology
                Keywords: aspergillus fumigatus, chronic pulmonary aspergillosis, echinocandin resistance, fks1 mutation, micafungin

                Comments

                Comment on this article

                scite_

                Similar content4

                See all similar

                Cited by29

                See all cited by

                Most referenced authors199

                See all reference authors