title: Pleiotropic effects of the vacuolar ABC transporter MLT1 of Candida albicans on cell function and virulence.
abstract: Among the several mechanisms that contribute to MDR (multidrug resistance), the overexpression of drug-efflux pumps belonging to the ABC (ATP-binding cassette) superfamily is the most frequent cause of resistance to antifungal agents. The multidrug transporter proteins Cdr1p and Cdr2p of the ABCG subfamily are major players in the development of MDR in Candida albicans Because several genes coding for ABC proteins exist in the genome of C. albicans, but only Cdr1p and Cdr2p have established roles in MDR, it is implicit that the other members of the ABC family also have alternative physiological roles. The present study focuses on an ABC transporter of C. albicans, Mlt1p, which is localized in the vacuolar membrane and specifically transports PC (phosphatidylcholine) into the vacuolar lumen. Transcriptional profiling of the mlt1∆/∆ mutant revealed a down-regulation of the genes involved in endocytosis, oxidoreductase activity, virulence and hyphal development. High-throughput MS-based lipidome analysis revealed that the Mlt1p levels affect lipid homoeostasis and thus lead to a plethora of physiological perturbations. These include a delay in endocytosis, inefficient sequestering of reactive oxygen species (ROS), defects in hyphal development and attenuated virulence. The present study is an emerging example where new and unconventional roles of an ABC transporter are being identified.
authors.affiliation: School of Life Sciences, Jawaharlal Nehru University, New Delhi 110067, India.
authors.forename: Nitesh Kumar
authors.initials: NK
authors.lastname: Khandelwal
authors.affiliation: Department of Microbial Pathogenicity Mechanisms, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knoell Institute Jena (HKI), D-07745 Jena, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Kaemmer
authors.affiliation: Department of Microbial Pathogenicity Mechanisms, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knoell Institute Jena (HKI), D-07745 Jena, Germany.
authors.forename: Toni M
authors.initials: TM
authors.lastname: Förster
authors.affiliation: Department of Molecular Genetics and Microbiology, Stony Brook University, 145 Life Sciences Building, Stony Brook, NY 11794, U.S.A. Department of Biochemistry, Lucknow University, Lucknow 226024, Uttar Pradesh, India.
authors.forename: Ashutosh
authors.initials: A
authors.lastname: Singh
authors.affiliation: Institute of Microbiology, University of Lausanne and University Hospital Center, Rue du Bugnon 48, Lausanne, CH-1011, Switzerland.
authors.forename: Alix T
authors.initials: AT
authors.lastname: Coste
authors.affiliation: Division of Infectious Diseases, Department of Medicine, University of Wisconsin, Madison, WI 53792, U.S.A. Department of Medical Microbiology and Immunology, University of Wisconsin, Madison, WI 53706, U.S.A.
authors.forename: David R
authors.initials: DR
authors.lastname: Andes
authors.affiliation: Department of Microbial Pathogenicity Mechanisms, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knoell Institute Jena (HKI), D-07745 Jena, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Hube
authors.affiliation: Institute of Microbiology, University of Lausanne and University Hospital Center, Rue du Bugnon 48, Lausanne, CH-1011, Switzerland.
authors.forename: Dominique
authors.initials: D
authors.lastname: Sanglard
authors.affiliation: Department of Microbiology and Molecular Genetics, Public Health Research Institute, New Jersey Medical School, Rutgers, The State University of New Jersey, 225 Warren Street, Newark, NJ 07103, U.S.A.
authors.forename: Neeraj
authors.initials: N
authors.lastname: Chauhan
authors.affiliation: Laboratory of Fungal Pathogenesis, Centre for DNA Fingerprinting and Diagnostics, Hyderabad 500001, Andhra Pradesh, India.
authors.forename: Rupinder
authors.initials: R
authors.lastname: Kaur
authors.affiliation: Département Génomes et Génétique, Institut Pasteur, Unité Biologie et Pathogénicité Fongiques, Paris, France, INRA, USC2019, Paris, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: d'Enfert
authors.affiliation: School of Life Sciences, Jawaharlal Nehru University, New Delhi 110067, India.
authors.forename: Alok Kumar
authors.initials: AK
authors.lastname: Mondal
authors.affiliation: Amity Institute of Integrative Sciences and Health, Amity University Haryana, Amity Education Valley, Gurgaon 122413, India rp47jnu@gmail.com rprasad@ggn.amity.edu.
authors.forename: Rajendra
authors.initials: R
authors.lastname: Prasad
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D001692:Biological Transport / Q000235:genetics / Q000502:physiology; D002176:Candida albicans / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity*; D019295:Computational Biology; D025141:Drug Resistance, Fungal; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism; D014617:Vacuoles / Q000378:metabolism*; D014774:Virulence / Q000235:genetics / Q000502:physiology
chemical_list: D018528:ATP-Binding Cassette Transporters; D005656:Fungal Proteins; D017382:Reactive Oxygen Species
keywords: ABC transporter; Candida albicans; MLT1; phosphotidylcholine; virulence