Initiation of phospholipomannan β-1,2 mannosylation involves Bmts with redundant activity, influences its cell wall location and regulates β-glucans homeostasis but is dispensable for Candida albicans systemic infection

Courjol, Flavie; Mille, Céline; Hall, Rebecca; Masset, Annick; Aijjou, R.; Gow, Neil A. R.; Poulain, Daniel; Jouault, Thierry; Fradin, Chantal

doi:10.1016/j.biochi.2015.09.032

Cited by 3 publications

(3 citation statements)

References 43 publications

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“…Infection model was based on protocols previously described (Courjol et al., 2016 ; MacCallum, 2013 ). In brief, mice were first rendered neutropenic by intraperitoneal injection of cyclophosphamide (75 mg/kg/d) for 2 d. To confirm neutropenia status of each animal, blood samples were obtained by retro-orbital bleeding before (day 0) and 24 h after (day 3) cyclophosphamide treatment for hematology analysis uses ABX Micros 60 (HORIBA, Montpellier, France).…”

Section: Methodsmentioning

confidence: 99%

Intravenous delivery of a liposomal formulation of voriconazole improves drug pharmacokinetics, tissue distribution, and enhances antifungal activity

et al. 2018

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Voriconazole (VCZ), a triazole with a large spectrum of action is one of the most recommended antifungal agents as the first line therapy against several clinically important systemic fungal infections, including those by Candida albicans. This antifungal has moderate water solubility and exhibits a nonlinear pharmacokinetic (PK) profile. By entrapping VCZ into liposomes, it is possible to circumvent certain downsides of the currently available product such as a reduction in the rate of its metabolization into an inactive form, avoidance of the toxicity of the sulfobutyl ether-beta-cyclodextrin (SBECD), vehicle used to increase its solubility. PKs and biodistribution of VCZ modified by encapsulation into liposomes resulted in improved antifungal activity, due to increased specificity and tissue penetration. In this work, liposomal VCZ resulted in AUC0–24/MIC ratio of 53.51 ± 11.12, whereas VFEND® resulted in a 2.5-fold lower AUC0–24/MIC ratio (21.51 ± 2.88), indicating favorable antimicrobial systemic activity. VCZ accumulation in the liver and kidneys was significantly higher when the liposomal form was used. Protection of the drug from biological degradation and reduced rate of metabolism leads to a 30% reduction of AUC of the inactive metabolite voriconazole-N-oxide (VNO) when the liposomal drug was administered. Liposomal VCZ presents an alternative therapeutic platform, leading to a safe and effective treatment against systemic fungal infections.

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Section: Methodsmentioning

confidence: 99%

Intravenous delivery of a liposomal formulation of voriconazole improves drug pharmacokinetics, tissue distribution, and enhances antifungal activity

et al. 2018

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“…The phosphomannan-deficient mnn4 Δ serotype B null mutant, the parental and its revertant were constructed as described (Hobson and others 2004 ). The bmt1 Δ (Fabre and others 2014 ), bmt2 Δ, bmt5 Δ (Mille and others 2012 ), and bmt1 Δ /bmt2 Δ /bmt5 Δ (Courjol and others 2015 ; Courjol and others 2016 ; Wilson and others 2000 ) β-mannosyl transferase mutants were constructed as previously described.…”

Section: Methodsmentioning

confidence: 99%

The Role of Dectin-2 for Host Defense Against Disseminated Candidiasis

Ifrim

Quintin

Courjol

et al. 2016

Journal of Interferon & Cytokine Research

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Despite the fact that Candida albicans is an important human fungal pathogen and Dectin-2 is a major pattern recognition receptor for fungi, our knowledge regarding the role of Dectin-2 for the host defense against disseminated candidiasis is limited. Dectin-2 deficient (Dectin-2−/−) mice were more susceptible to systemic candidiasis, and the susceptibility was mirrored by an elevated fungal load in the kidneys that correlated with the presence of large inflammatory foci. Phagocytosis of Candida by the macrophages lacking the Dectin-2 receptor was moderately decreased, while production of most of the macrophage-derived cytokines from Dectin-2−/− mice with systemic candidiasis was decreased. No striking differences among several Candida mutants defective in mannans could be detected between naïve wild-type and Dectin-2−/− mice, apart from the β-mannan-deficient bmt1Δ/bmt2Δ/bmt5Δ triple mutant, suggesting that β-mannan may partially mask α-mannan detection, which is the major fungal structure recognized by Dectin-2. Deciphering the mechanisms responsible for host defense against the majority of C. albicans strains represents an important step in understanding the pathophysiology of systemic candidiasis, which might lead to the development of novel immunotherapeutic strategies.

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“…To identify molecules expressing β-Man epitopes and members of the BMT gene family responsible for sequential addition of β-Man on these substates Besides PPM, the epitope is shared by numerous mannoproteins [23] High expression and specific patterns of distribution exist in C. albicans, tropicalis glabrata [9] The epitope is shared by GPI anchored, PIR and secreted major C. albicans virulence factors [30] The epitope allows characterization of a glycolipid named phopholipomannan, a member of the manno-inositol family with strong immunomodulatory properties [29,32,45] Discovery of BMT gene family responsible for synthesis of β-mannosides composed of 9 members and precise definition of Bmts 1-6 activities depending on the acceptor molecule [32,33,96] Table 1. Cont.…”

Section: Western Blottingmentioning

confidence: 99%

Antibodies as Models and Tools to Decipher Candida albicans Pathogenic Development: Review about a Unique Monoclonal Antibody Reacting with Immunomodulatory Adhesins

Leroy

Lecointe

Coulon

et al. 2023

JoF

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Candidiasis, caused mainly by Candida albicans, a natural commensal of the human digestive tract and vagina, is the most common opportunistic fungal infection at the mucosal and systemic levels. Its high morbi–mortality rates have led to considerable research to identify the molecular mechanisms associated with the switch to pathogenic development and to diagnose this process as accurately as possible. Since the 1980s, the advent of monoclonal antibody (mAb) technology has led to significant progress in both interrelated fields. This linear review, intended to be didactic, was prompted by considering how, over several decades, a single mAb designated 5B2 contributed to the elucidation of the molecular mechanisms of pathogenesis based on β-1,2-linked oligomannoside expression in Candida species. These contributions starting from the structural identification of the minimal epitope as a di-mannoside from the β-1,2 series consisted then in the demonstration that it was shared by a large number of cell wall proteins differently anchored in the cell wall and the discovery of a cell wall glycoplipid shed by the yeast in contact of host cells, the phospholipomannan. Cytological analysis revealed an overall highly complex epitope expression at the cell surface concerning all growth phases and a patchy distribution resulting from the merging of cytoplasmic vesicles to plasmalema and further secretion through cell wall channels. On the host side, the mAb 5B2 led to identification of Galectin-3 as the human receptor dedicated to β-mannosides and signal transduction pathways leading to cytokine secretion directing host immune responses. Clinical applications concerned in vivo imaging of Candida infectious foci, direct examination of clinical samples and detection of circulating serum antigens that complement the Platelia Ag test for an increased sensitivity of diagnosis. Finally, the most interesting character of mAb 5B2 is probably its ability to reveal C. albicans pathogenic behaviour in reacting specifically with vaginal secretions from women infected versus colonized by this species as well as to display higher reactivity with strains isolated in pathogenic circumstances or even linked to an unfavourable prognosis for systemic candidiasis. Together with a detailed referenced description of these studies, the review provides a complementary reading frame by listing the wide range of technologies involving mAb 5B2 over time, evidencing a practical robustness and versatility unique so far in the Candida field. Finally, the basic and clinical perspectives opened up by these studies are briefly discussed with regard to prospects for future applications of mAb 5B2 in current research challenges.

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Initiation of phospholipomannan β-1,2 mannosylation involves Bmts with redundant activity, influences its cell wall location and regulates β-glucans homeostasis but is dispensable for Candida albicans systemic infection

Cited by 3 publications

References 43 publications

Intravenous delivery of a liposomal formulation of voriconazole improves drug pharmacokinetics, tissue distribution, and enhances antifungal activity

Intravenous delivery of a liposomal formulation of voriconazole improves drug pharmacokinetics, tissue distribution, and enhances antifungal activity

The Role of Dectin-2 for Host Defense Against Disseminated Candidiasis

Antibodies as Models and Tools to Decipher Candida albicans Pathogenic Development: Review about a Unique Monoclonal Antibody Reacting with Immunomodulatory Adhesins

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