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      Contributions of the Biofilm Matrix to Candida Pathogenesis

      review-article
      * ,
      Journal of Fungi
      MDPI
      Candida, matrix, biofilm, immunity, drug resistance

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          Abstract

          In healthcare settings, Candida spp. cause invasive disease with high mortality. The overwhelming majority of cases are associated with the use of critically-needed medical devices, such as vascular catheters. On the surface of these indwelling materials, Candida forms resilient, adherent biofilm communities. A hallmark characteristic of this process is the production of an extracellular matrix, which promotes fungal adhesion and provides protection from external threats. In this review, we highlight the medical relevance of device-associated Candida biofilms and draw attention to the process of Candida-biofilm-matrix production. We provide an update on the current understanding of how biofilm extracellular matrix contributes to pathogenicity, particularly through its roles in the promoting antifungal drug tolerance and immune evasion.

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          Most cited references62

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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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            Attributable mortality of nosocomial candidemia, revisited.

            We reexamined the attributable mortality of nosocomial candidemia 15 years after a retrospective cohort study performed at our hospital demonstrated an attributable mortality of 38%. For all episodes of nosocomial candidemia between 1 July 1997 and 30 June 2001, we matched control patients with case patients by age, sex, date of hospital admission, underlying disease(s), length of time at risk, and surgical procedure(s). We analyzed 108 matched pairs. There were no statistically significant differences in age, sex, underlying disease(s), time at risk, surgical procedure, or vital signs at admission between cases and controls. The crude mortality among case patients was 61% (66 of 108 patients), compared with 12% (13 of 108) among control patients, for an attributable mortality of 49% (95% CI, 38%-60%). Nosocomial candidemia is still associated with an extremely high crude and attributable mortality--much higher than that expected from underlying disease alone.
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              Impact of treatment strategy on outcomes in patients with candidemia and other forms of invasive candidiasis: a patient-level quantitative review of randomized trials.

              Invasive candidiasis (IC) is an important healthcare-related infection, with increasing incidence and a crude mortality exceeding 50%. Numerous treatment options are available yet comparative studies have not identified optimal therapy. We conducted an individual patient-level quantitative review of randomized trials for treatment of IC and to assess the impact of host-, organism-, and treatment-related factors on mortality and clinical cure. Studies were identified by searching computerized databases and queries of experts in the field for randomized trials comparing the effect of ≥2 antifungals for treatment of IC. Univariate and multivariable analyses were performed to determine factors associated with patient outcomes. Data from 1915 patients were obtained from 7 trials. Overall mortality among patients in the entire data set was 31.4%, and the rate of treatment success was 67.4%. Logistic regression analysis for the aggregate data set identified increasing age (odds ratio [OR], 1.01; 95% confidence interval [CI], 1.00-1.02; P = .02), the Acute Physiology and Chronic Health Evaluation II score (OR, 1.11; 95% CI, 1.08-1.14; P = .0001), use of immunosuppressive therapy (OR, 1.69; 95% CI, 1.18-2.44; P = .001), and infection with Candida tropicalis (OR, 1.64; 95% CI, 1.11-2.39; P = .01) as predictors of mortality. Conversely, removal of a central venous catheter (CVC) (OR, 0.50; 95% CI, .35-.72; P = .0001) and treatment with an echinocandin antifungal (OR, 0.65; 95% CI, .45-.94; P = .02) were associated with decreased mortality. Similar findings were observed for the clinical success end point. Two treatment-related factors were associated with improved survival and greater clinical success: use of an echinocandin and removal of the CVC.
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                Author and article information

                Journal
                J Fungi (Basel)
                J Fungi (Basel)
                jof
                Journal of Fungi
                MDPI
                2309-608X
                03 February 2020
                March 2020
                : 6
                : 1
                : 21
                Affiliations
                Departments of Medicine and Medical Microbiology & Immunology, University of Wisconsin-Madison, Madison, WI 53706, USA; dra@ 123456medicine.wisc.edu
                Author notes
                Article
                jof-06-00021
                10.3390/jof6010021
                7151000
                32028622
                230ee5cc-bb8f-4378-afb2-8ab70049668f
                © 2020 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
                : 09 January 2020
                : 30 January 2020
                Categories
                Review

                candida,matrix,biofilm,immunity,drug resistance
                candida, matrix, biofilm, immunity, drug resistance

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