Clinical Impact of Antifungal Susceptibility, Biofilm Formation and Mannoside Expression of Candida Yeasts on the Outcome of Invasive Candidiasis in ICU: An Ancillary Study on the Prospective AmarCAND2 Cohort

Background: The link between Candida phenotypical characteristics and invasive candidiasis (IC) prognosis is still partially unknown.Methods:Candida strains isolated during the AmarCAND2 study were centrally analyzed for species identification, antifungal susceptibility, biofilm formation, and expression of surface and glycoconjugate mannosides. Correlation between these phenotypical features and patient outcome was sought using a multivariable Cox survival model.Results:Candida albicans was predominant (65.4%, n = 285), with a mortality rate significantly lower than that in patients with non-albicans strains [HR 0.67 (0.46–1.00), p = 0.048]. The rate of fluconazole-resistant strains was low (C. albicans and Candida glabrata: 3.5 and 6.2%, respectively) as well as caspofungin-resistant ones (1 and 3.1%, respectively). Early biofilm formation was less frequent among C. albicans (45.4%) than among non-albicans (81.2%). While the strains of C. albicans showed variable levels of surface mannosides expression, strains isolated from candidemia exhibited a high expression of β-man, which was correlated with an increased mortality (p = 0.02).Conclusion:Candida albicans IC were associated with lower mortality, and with strains that exhibited less frequently early biofilm formation than non-albicans strains. A high expression of β-man was associated with increased IC mortality. Further studies are warranted to confirm this data and to evaluate other virulence factors in yeasts

The pathogenic and colonization potential of Candida africana

The Candida albicans population displays high genetic diversity illustrated by 18-well differentiated genetic clusters. Cluster 13, also known as Candida africana, is an outlying cluster and includes strains first described as atypical C. albicans isolates of vaginal origin, showing apparent tropism for the female genital tract. In our study, we combined in vitro, and in vivo models to explore the colonization and pathogenic potential of C. africana. We report that C. africana has similar fitness to C. albicans when it comes to colonization of the oral and vaginal mucosa, however it has decreased fitness in gastro-intestinal colonization and systemic infection. Interestingly, despite high population homogeneity, our in vitro data highlighted for the first time a variability in terms of growth rate, biofilm formation and filamentation properties between C. africana strains. Overall, our data lays the foundations for exploring specific features of C. africana that might contribute to its apparent niche restriction

Synergy of the antibiotic colistin with echinocandin antifungals in Candida species.

International audienceOBJECTIVES: Candida albicans is the most prevalent fungal pathogen of humans, causing a wide range of infections from harmless superficial to severe systemic infections. Improvement of the antifungal arsenal is needed since existing antifungals can be associated with limited efficacy, toxicity and antifungal resistance. Here we aimed to identify compounds that act synergistically with echinocandin antifungals and that could contribute to a faster reduction of the fungal burden. METHODS: A total of 38 758 compounds were tested for their ability to act synergistically with aminocandin, a β-1,3-glucan synthase inhibitor of the echinocandin family of antifungals. The synergy between echinocandins and an identified hit was studied with chemogenomic screens and testing of individual Saccharomyces cerevisiae and C. albicans mutant strains. RESULTS: We found that colistin, an antibiotic that targets membranes in Gram-negative bacteria, is synergistic with drugs of the echinocandin family against all Candida species tested. The combination of colistin and aminocandin led to faster and increased permeabilization of C. albicans cells than either colistin or aminocandin alone. Echinocandin susceptibility was a prerequisite to be able to observe the synergy. A large-scale screen for genes involved in natural resistance of yeast cells to low doses of the drugs, alone or in combination, identified efficient sphingolipid and chitin biosynthesis as necessary to protect S. cerevisiae and C. albicans cells against the antifungal combination. CONCLUSIONS: These results suggest that echinocandin-mediated weakening of the cell wall facilitates colistin targeting of fungal membranes, which in turn reinforces the antifungal activity of echinocandins

Systematic Gene Overexpression in Candida albicans identifies a Regulator of Early Adaptation to the Mammalian Gut

We are grateful to members of the genomics core facility (PF2, Génopole) for the availability of the microarray scanner and the Alain Jacquier’s lab for making the GenePix software available. We are grateful to Drs. Suzanne Noble and Aaron Mitchell for providing C. albicans mutant collections. We thank all members of the Fungal Biology & Pathogenicity Unit, particularly Drs. Anne Neville and Adeline Feri for their numerous insights during the course of this project. This work has been supported by grants from the Agence Nationale de la Recherche (KANJI, ANR-08-MIE-033-01 to C.d’E. and F.D.; ERA-Net Infect-ERA, FUNCOMPATH, ANR-14-IFEC-0004; and CANDIHUB, ANR-14-CE-0018 to C.d’E.), the French Government’s Investissement d’Avenir program (Laboratoire d’Excellence Integrative Biology of Emerging Infectious Diseases, ANR-10-LABX-62-IBEID to C.d’E.; Institut de Recherche Technologique BIOASTER, ANR-10-AIRT-03 to C.d’E., F.D. and T.J.), the European Commission (FinSysB PITN-GA-2008-214004 to C.d’E.) and the Wellcome Trust (The Candida albicans ORFeome project, WT088858MA to C.d’E. and C.M.). C.M. acknowledges support from the Medical Research Council, UK (New Investigator Award, G0400284), the MRC Centre for Medical Mycology (MR/N006364/1) and the University of Aberdeen. S.Z. is an Institut Pasteur International Network Affiliate Program Fellow. S.Z., L.v.W. and A.H.C. were the recipients of post-doctoral fellowships from the European Commission (FINSysB, PITN-GA-2008-214004 to S.Z.), the Agence Nationale de la Recherche (KANJI, ANR-08-MIE-033-01 to S.Z.; ERA-Net Infect-ERA, FUNCOMPATH, ANR-14-IFEC-0004 to A.H.C.; CANDIHUB, ANR-14-CE-0018 to L.v.W) and the French Government’s Investissement d’Avenir program (Institut de Recherche Technologique BIOASTER, ANR-10-AIRT-03 to S.Z. and A.H.C.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

Unveiling Candida albicans intestinal carriage in healthy volunteers : the role of micro- and mycobiota, diet, host genetics and immune response

Acknowledgements This work was supported by a grant from Agence Nationale de la Recherche (FunComPath ANR-14-IFEC-0004), the French Government’s Investissement d’Avenir program (Laboratoire d’Excellence Integrative Biology of Emerging Infectious Diseases [ANR10-LABX-62-IBEID], and [ANR-10-LABX-69-01]), the European Union's Horizon 2020 research and innovation program under the Marie Sklodowska-Curie action, Innovative Training Network (FunHoMic; Grant No. 812969 ), and the European Union's Horizon 2020 Research and Innovation Program (HDM-FUN, Grant No. 847507). AWW and the Rowett Institute (University of Aberdeen) received core funding support from the Scottish Government’s Rural and Environmental Sciences and Analytical Services (RESAS).Peer reviewedPublisher PD

A CO2 sensing module modulates β-1,3-glucan exposure in Candida albicans.

This work was funded by a program grant to A.J.P.B., N.A.R.G., L.P.E., and M.G.N. from the UK Medical Research Council [www.mrc.ac.uk: MR/M026663/1, MR/M026663/2]. The work was also supported by the Medical Research Council Centre for Medical Mycology [MR/N006364/1, MR/N006364/2], by a grant to C.d.E. from the European Commission [FunHoMic: H2020-MSCA-ITN-2018–812969], and by the Wellcome Trust via Investigator, Collaborative, Equipment, Strategic and Biomedical Resource awards [www.wellcome.ac.uk: 075470, 086827, 093378, 097377, 099197, 101873, 102705, 200208, 217163, 224323]. Work in the d’Enfert laboratory was supported by grants from the Agence Nationale de Recherche (ANR-10-LABX-62-IBEID) and the Swiss National Science Foundation (Sinergia CRSII5_173863/1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission.Peer reviewedPublisher PD

The impact of the Fungus-Host-Microbiota interplay upon Candida albicans infections : current knowledge and new perspectives

ACKNOWLEDGEMENTS: We thank our friends and colleagues in the medical mycology, fungal immunology and microbiota fields for many thought-provoking discussions. FUNDING: We received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie action, Innovative Training Network: FunHoMic; grant N° 812969. CdE received funding from the French Government ‘Investissement d’Avenir’ program (Laboratoire d’Excellence Integrative Biology of Emerging Infectious Diseases, ANR-10-LABX-62-IBEID), the Agence Nationale de la Recherche (ERA-Net Infect-ERA, FUNCOMPATH, ANR-14-IFEC-0004), the EU Horizon2020 consortium “Host-Directed Medicine in invasive FUNgal infections” - HDM-FUN (Grant Agreement 847507). SLL and CdE received funding from the Swiss National Science Foundation (Sinergia program, #CRSII5_173863). BIOASTER received funding from the French Government ‘Investissement d’Avenir’ program (Grant No. ANR-10-AIRT-03). MSG was supported by a Humboldt Research Fellowship for Postdoctoral Researchers by the Alexander von Humboldt-Foundation and the Deutsche Forschungsgemeinschaft (DFG) Emmy Noether Program (project no. 434385622 / GR 5617/1-1). BH was supported by the Deutsche Forschungsgemeinschaft (DFG) project Hu 532/20-1, project C1 within the Collaborative Research Centre (CRC)/Transregio 124 FungiNet and the Balance of the Microverse Cluster under Germany´s Excellence Strategy – EXC 2051 – Project-ID 390713860, the EU Horizon2020 consortium “Host-Directed Medicine in invasive FUNgal infections” - HDM-FUN (Grant Agreement 847507), the Leibniz Association Campus InfectoOptics SAS-2015-HKI-LWC and the Wellcome Trust (215599/Z/19/Z). IDJ was supported by the Deutsche orschungsgemeinschaft (DFG) project C5 within the Collaborative Research Centre (CRC)/Transregio 124 FungiNet and the Balance of the Microverse Cluster under Germany´s Excellence Strategy – EXC 2051 – Project-ID 390713860, the Leibniz Association Campus InfectoOptics SAS-2015-HKI-LWC and the Wellcome Trust (Grant 215599/Z/19/Z). CM received funding from the the Instituto de Salud Carlos III/FEDER. MGN was supported by an ERC Advanced Grant (#833247) and a Spinoza grant of the Netherlands Organization for Scientific Research. CAM was supported by EU Horizon2020 consortium “Host-Directed Medicine in invasive FUNgal infections” -HDM-FUN (Grant Agreement 847507) and the Wellcome Trust Strategic Award for Medical Mycology and Fungal Immunology (097377/Z/11/Z). AWW receives core funding support from the Scottish Government’s Rural and Environment Science and Analytical Services (RESAS). AJPB was supported by a programme grant from the UK Medical Research Council (MR/M026663/1) and by the Medical Research Council Centre for Medical Mycology at the University of Exeter (MR/N006364/1).Peer reviewedPublisher PD

Epidémiologie de la colonisation fongique des expectorations des enfants atteints de mucoviscidose (Hôpital Necker-Enfant-Malades)

PARIS-BIUP (751062107) / SudocSudocFranceF

Tracing the Origin of Invasive Fungal Infections

International audienceInvasive fungal infections are a major cause of mortality in immunocompromised patients. By using high-resolution sequencing, Zhai et al. provide insight into translocation of Candida strains from the gut mycobiota to the bloodstream of transplanted patients. Microbiota-driven diagnostic methods could rapidly emerge for preventing deadly fungal infections

Candida albicans commensalism in the gastrointestinal tract.

International audienceCandida albicans is a polymorphic yeast species that often forms part of the commensal gastrointestinal mycobiota of healthy humans. It is also an important opportunistic pathogen. A tripartite interaction involving C. albicans, the resident microbiota and host immunity maintains C. albicans in its commensal form. The influence of each of these factors on C. albicans carriage is considered herein, with particular focus on the mycobiota and the approaches used to study it, models of gastrointestinal colonization by C. albicans, the C. albicans genes and phenotypes that are necessary for commensalism and the host factors that influence C. albicans carriage