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      Biofilm Formation and Resistance to Fungicides in Clinically Relevant Members of the Fungal Genus Fusarium

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          Abstract

          Clinically relevant members of the fungal genus, Fusarium, exhibit an extraordinary genetic diversity and cause a wide spectrum of infections in both healthy individuals and immunocompromised patients. Generally, Fusarium species are intrinsically resistant to all systemic antifungals. We investigated whether the presence or absence of the ability to produce biofilms across and within Fusarium species complexes is linked to higher resistance against antifungals. A collection of 41 Fusarium strains, obtained from 38 patients with superficial and systemic infections, and three infected crops, were tested, including 25 species within the Fusarium fujikuroi species complex, 14 from the Fusarium solani species complex (FSSC), one Fusarium dimerum species complex, and one Fusarium oxysporum species complex isolate. Of all isolates tested, only seven strains from two species of FSSC, five F. petroliphilum and two F. keratoplasticum strains, recovered from blood, nail scrapings, and nasal biopsy samples, could produce biofilms under the tested conditions. In the liquid culture tested, sessile biofilm-forming Fusarium strains exhibited elevated minimum inhibitory concentrations (MICs) for amphotericin B, voriconazole, and posaconazole, compared to their planktonic counterparts, indicating that the ability to form biofilm may significantly increase resistance. Collectively, this suggests that once a surface adherent biofilm has been established, therapies designed to kill planktonic cells of Fusarium are ineffective.

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          Most cited references40

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          Biofilm formation by the fungal pathogen Candida albicans: development, architecture, and drug resistance.

          Biofilms are a protected niche for microorganisms, where they are safe from antibiotic treatment and can create a source of persistent infection. Using two clinically relevant Candida albicans biofilm models formed on bioprosthetic materials, we demonstrated that biofilm formation proceeds through three distinct developmental phases. These growth phases transform adherent blastospores to well-defined cellular communities encased in a polysaccharide matrix. Fluorescence and confocal scanning laser microscopy revealed that C. albicans biofilms have a highly heterogeneous architecture composed of cellular and noncellular elements. In both models, antifungal resistance of biofilm-grown cells increased in conjunction with biofilm formation. The expression of agglutinin-like (ALS) genes, which encode a family of proteins implicated in adhesion to host surfaces, was differentially regulated between planktonic and biofilm-grown cells. The ability of C. albicans to form biofilms contrasts sharply with that of Saccharomyces cerevisiae, which adhered to bioprosthetic surfaces but failed to form a mature biofilm. The studies described here form the basis for investigations into the molecular mechanisms of Candida biofilm biology and antifungal resistance and provide the means to design novel therapies for biofilm-based infections.
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            Candida biofilms: an update.

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              Fungal Biofilm Resistance

              Fungal biofilm infections have become increasingly recognised as a significant clinical problem. One of the major reasons behind this is the impact that these have upon treatment, as antifungal therapy often fails and surgical intervention is required. This places a large financial burden on health care providers. This paper aims to illustrate the importance of fungal biofilms, particularly Candida albicans, and discusses some of the key fungal biofilm resistance mechanisms that include, extracellular matrix (ECM), efflux pump activity, persisters, cell density, overexpression of drug targets, stress responses, and the general physiology of the cell. The paper demonstrates the multifaceted nature of fungal biofilm resistance, which encompasses some of the newest data and ideas in the field.
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                Author and article information

                Journal
                J Fungi (Basel)
                J Fungi (Basel)
                jof
                Journal of Fungi
                MDPI
                2309-608X
                23 January 2018
                March 2018
                : 4
                : 1
                : 16
                Affiliations
                [1 ]Department of Mycology, Kayseri Education and Research Hospital, Kayseri 38010, Turkey; hafize.sav@ 123456hotmail.com
                [2 ]Department of Microbiology and Immunology, Center of Excellence for Infection Biology and Antimicrobial Pharmacology, Tehran 1969753491, Iran; halehrafati@ 123456gmail.com
                [3 ]Division of Mycology, Department of Microbiology, Faculty of Medicine, University of Osmangazi, Eskişehir 26040, Turkey; dryaseminoz@ 123456gmail.com
                [4 ]Division of Mycology, Department of Medical Microbiology, University of Health Sciences Bursa High Specialization Training and Research Hospital, Bursa 16320, Turkey; bdalyan@ 123456yahoo.com
                [5 ]Department of Microbiology, Faculty of Medicine, Uludağ University, Bursa 16059, Turkey; bener@ 123456uludag.edu.tr
                [6 ]Department of Medical Parasitology and Mycology, School of Medicine, Qazvin University of Medical Sciences, Qazvin 34156-13911, Iran; faezehmohamadi119@ 123456yahoo.com
                [7 ]Division of Mycology, Department of Microbiology, Faculty of Medicine, University of Çukurova, Adana 01330, Turkey; macitilkit@ 123456gmail.com
                [8 ]Westerdijk Fungal Biodiversity Institute, 3584 CT Utrecht, The Netherlands; anne.vandiepeningen@ 123456wur.nl
                [9 ]Department of Medical Microbiology, Center of Expertise in Mycology Radboudumc/CWZ, 6500 HB Nijmegen, The Netherlands
                [10 ]Invasive Fungi Research Center, Mazandaran University of Medical Sciences, Sari 48175-1665, Iran
                Author notes
                [* ]Correspondence: Seyedmousavi@ 123456nih.gov ; Tel.: +1-(301)-402-5139
                [†]

                Current address: BU Biointeracton and Plant Health, Wageningen University and Research, Droevendaalsesteeg 1, 6700AA Wageningen, The Netherlands.

                [‡]

                Current address: Molecular Microbiology Section, Laboratory of Clinical Infectious Diseases (LCID), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD 20892, USA.

                Author information
                https://orcid.org/0000-0003-2243-7644
                https://orcid.org/0000-0002-9822-2626
                https://orcid.org/0000-0002-1174-4182
                Article
                jof-04-00016
                10.3390/jof4010016
                5872319
                29371509
                229d6723-f394-4d47-96f3-7d037a0c698b
                © 2018 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 11 November 2017
                : 16 January 2018
                Categories
                Article

                biofilms,fusarium solani species complex,fusarium petroliphilum,fusarium keratoplasticum,antifungal resistance

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