title: Novel role of a family of major facilitator transporters in biofilm development and virulence of Candida albicans.
abstract: The QDR (quinidine drug resistance) family of genes encodes transporters belonging to the MFS (major facilitator superfamily) of proteins. We show that QDR transporters, which are localized to the plasma membrane, do not play a role in drug transport. Hence, null mutants of QDR1, QDR2 and QDR3 display no alterations in susceptibility to azoles, polyenes, echinocandins, polyamines or quinolines, or to cell wall inhibitors and many other stresses. However, the deletion of QDR genes, individually or collectively, led to defects in biofilm architecture and thickness. Interestingly, QDR-lacking strains also displayed attenuated virulence, but the strongest effect was observed with qdr2∆, qdr3∆ and in qdr1/2/3∆ strains. Notably, the attenuated virulence and biofilm defects could be reversed upon reintegration of QDR genes. Transcripts profiling confirmed differential expression of many biofilm and virulence-related genes in the deletion strains as compared with wild-type Candida albicans cells. Furthermore, lipidomic analysis of QDR-deletion mutants suggests massive remodelling of lipids, which may affect cell signalling, leading to the defect in biofilm development and attenuation of virulence. In summary, the results of the present study show that QDR paralogues encoding MFS antiporters do not display conserved functional linkage as drug transporters and perform functions that significantly affect the virulence of C. albicans.
authors.affiliation: *Membrane Biology Laboratory, School of Life Sciences, Jawaharlal Nehru University, New Delhi 110067, India.
authors.forename: Abdul Haseeb
authors.initials: AH
authors.lastname: Shah
authors.affiliation: *Membrane Biology Laboratory, School of Life Sciences, Jawaharlal Nehru University, New Delhi 110067, India.
authors.forename: Ashutosh
authors.initials: A
authors.lastname: Singh
authors.affiliation: *Membrane Biology Laboratory, School of Life Sciences, Jawaharlal Nehru University, New Delhi 110067, India.
authors.forename: Sanjiveeni
authors.initials: S
authors.lastname: Dhamgaye
authors.affiliation: †Public Health Research Institute and Department of Microbiology and Molecular Genetics, 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: ‡Institut de Microbiologie, University of Lausanne and University Hospital Center, Lausanne, Switzerland.
authors.forename: Patrick
authors.initials: P
authors.lastname: Vandeputte
authors.affiliation: §Laboratory of Fungal Pathogenesis, Centre for DNA Fingerprinting and Diagnostics, Hyderabad, Andhra Pradesh, India.
authors.forename: Korivi Jyothiraj
authors.initials: KJ
authors.lastname: Suneetha
authors.affiliation: §Laboratory of Fungal Pathogenesis, Centre for DNA Fingerprinting and Diagnostics, Hyderabad, Andhra Pradesh, India.
authors.forename: Rupinder
authors.initials: R
authors.lastname: Kaur
authors.affiliation: ∥Center for Medical Mycology, Department of Dermatology, Case Western Reserve University, Cleveland, OH 44106, U.S.A.
authors.forename: Pranab K
authors.initials: PK
authors.lastname: Mukherjee
authors.affiliation: ∥Center for Medical Mycology, Department of Dermatology, Case Western Reserve University, Cleveland, OH 44106, U.S.A.
authors.forename: Jyotsna
authors.initials: J
authors.lastname: Chandra
authors.affiliation: ∥Center for Medical Mycology, Department of Dermatology, Case Western Reserve University, Cleveland, OH 44106, U.S.A.
authors.forename: Mahmoud A
authors.initials: MA
authors.lastname: Ghannoum
authors.affiliation: ‡Institut de Microbiologie, University of Lausanne and University Hospital Center, Lausanne, Switzerland.
authors.forename: Dominique
authors.initials: D
authors.lastname: Sanglard
authors.affiliation: *Membrane Biology Laboratory, School of Life Sciences, Jawaharlal Nehru University, New Delhi 110067, India.
authors.forename: Shyamal K
authors.initials: SK
authors.lastname: Goswami
authors.affiliation: *Membrane Biology Laboratory, School of Life Sciences, Jawaharlal Nehru University, New Delhi 110067, India.
authors.forename: Rajendra
authors.initials: R
authors.lastname: Prasad
mesh_terms: D000818:Animals; D018441:Biofilms / Q000187:drug effects* / Q000254:growth & development; D002176:Candida albicans / Q000187:drug effects* / Q000472:pathogenicity; D002177:Candidiasis / Q000235:genetics; D025141:Drug Resistance, Fungal / Q000235:genetics*; D005800:Genes, Fungal / Q000502:physiology; D008563:Membrane Lipids / Q000378:metabolism; D021962:Membrane Microdomains / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000235:genetics; D051379:Mice; D053038:Quorum Sensing / Q000502:physiology; D014774:Virulence / Q000235:genetics*
chemical_list: D008563:Membrane Lipids; D026901:Membrane Transport Proteins