A CO 2 sensing module modulates β-1,3-glucan exposure in Candida albicans

Avelar, Gabriela; Pradhan, Arnab; Ma, Qinxi; Hickey, Emer; Leaves, Ian; Liddle, Corin; Rodriguez Rondon, Alejandra; Kaune, Ann-Kristin; Shaw, Sophie; Maufrais, Corinne; Sertour, Natacha; Bain, Judith; Larcombe, Daniel; de Assis, Leandro; Netea, Mihai; Munro, Carol; Childers, Delma; Erwig, Lars; Brown, Gordon; Gow, Neil; Bougnoux, Marie-Elisabeth; D'Enfert, Christophe; Brown, Alistair; University of Aberdeen; University of Exeter; Biologie et Pathogénicité fongiques - Fungal Biology and Pathogenicity  ; Institut Pasteur [Paris] -Université Paris Cité -Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement; Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB ; Institut Pasteur [Paris] -Université Paris Cité; Radboud University Medical Center [Nijmegen]; Universität Bonn = University of Bonn; Johnson & Johnson Corporation; Hôpital Necker - Enfants Malades [AP-HP] ; Assistance publique - Hôpitaux de Paris; Université Paris Cité; 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  and the Swiss National Science Foundation .; ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases; European Project: 812969,H2020-MSCA-ITN-2018,FunHoMic

A CO 2 sensing module modulates β-1,3-glucan exposure in Candida albicans

2024

Avelar, Gabriela | Pradhan, Arnab | Ma, Qinxi | Hickey, Emer | Leaves, Ian | Liddle, Corin | Rodriguez Rondon, Alejandra | Kaune, Ann-Kristin | Shaw, Sophie | Maufrais, Corinne | Sertour, Natacha | Bain, Judith | Larcombe, Daniel | de Assis, Leandro | Netea, Mihai | Munro, Carol | Childers, Delma | Erwig, Lars | Brown, Gordon | Gow, Neil | Bougnoux, Marie-Elisabeth | D'Enfert, Christophe | Brown, Alistair | University of Aberdeen | University of Exeter | Biologie et Pathogénicité fongiques - Fungal Biology and Pathogenicity (BPF) ; Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE) | Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB ; Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité) | Radboud University Medical Center [Nijmegen] (RadboudUMC) | Universität Bonn = University of Bonn | Johnson & Johnson Corporation | Hôpital Necker - Enfants Malades [AP-HP] ; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP) | Université Paris Cité (UPCité) | 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). | ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010) | European Project: 812969,H2020-MSCA-ITN-2018,FunHoMic(2019)

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英语. Microbial species capable of co-existing with healthy individuals, such as the commensal fungus Candida albicans, exploit multifarious strategies to evade our immune defenses. These strategies include the masking of immunoinflammatory pathogen-associated molecular patterns (PAMPs) at their cell surface. We reported previously that C. albicans actively reduces the exposure of the proinflammatory PAMP, β-1,3-glucan, at its cell surface in response to host-related signals such as lactate and hypoxia. Here, we show that clinical isolates of C. albicans display phenotypic variability with respect to their lactate- and hypoxia-induced β-1,3-glucan masking. We have exploited this variability to identify responsive and non-responsive clinical isolates. We then performed RNA sequencing on these isolates to reveal genes whose expression patterns suggested potential association with lactate- or hypoxia-induced β-1,3-glucan masking. The deletion of two such genes attenuated masking: PHO84 and NCE103. We examined NCE103-related signaling further because NCE103 has been shown previously to encode carbonic anhydrase, which promotes adenylyl cyclase-protein kinase A (PKA) signaling at low CO2 levels. We show that while CO2 does not trigger β-1,3-glucan masking in C. albicans, the Sch9-Rca1-Nce103 signaling module strongly influences β-1,3-glucan exposure in response to hypoxia and lactate. In addition to identifying a new regulatory module that controls PAMP exposure in C. albicans, our data imply that this module is important for PKA signaling in response to environmental inputs other than CO2.

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