Phylogenetic and syntenic analyses of the 12-spanner drug:H(+) antiporter family 1 (DHA1) in pathogenic Candida species: evolution of MDR1 and FLU1 genes

Paulo Jorge Dias; Isabel Sá-Correia

doi:10.1016/j.ygeno.2014.05.005

Phylogenetic and syntenic analyses of the 12-spanner drug:H(+) antiporter family 1 (DHA1) in pathogenic Candida species: evolution of MDR1 and FLU1 genes

Genomics. 2014 Jul;104(1):45-57. doi: 10.1016/j.ygeno.2014.05.005. Epub 2014 Jun 5.

Authors

Paulo Jorge Dias¹, Isabel Sá-Correia²

Affiliations

¹ IBB - Institute for Biotechnology and Bioengineering, Centre for Biological and Chemical Engineering, Department of Bioengineering, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal. Electronic address: pjdias@tecnico.ulisboa.pt.
² IBB - Institute for Biotechnology and Bioengineering, Centre for Biological and Chemical Engineering, Department of Bioengineering, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal. Electronic address: isacorreia@tecnico.ulisboa.pt.

PMID: 24907457
DOI: 10.1016/j.ygeno.2014.05.005

Abstract

Candida albicans and other pathogenic Candida species can develop resistance to clinical fungicides through active drug export mediated by multidrug efflux pumps, in particular by members of the drug:H(+) antiporter family 1 (DHA1). The DHA1 proteins encoded in the genomes of 31 hemiascomycetous strains from 25 species were identified and homology relationships between these proteins and the functionally characterised DHA1 in the model yeast Saccharomyces cerevisiae were established. Gene neighbourhood analysis allowed the reconstruction of sixteen DHA1 lineages conserved during the CTG complex species evolution. The evolutionary history of C. albicans MDR1 and FLU1 genes and Candida dubliniensis, Candida tropicalis and Candida parapsilosis MDR1 genes was detailed. Candida genomes show an abundant number of MDR1 and FLU1 homologues but the chromosome environment where MDR1 homologues reside was poorly conserved during evolution. Gene duplication and loss are major mechanisms underlying the evolution of the DHA1 genes in Candida species.

Keywords: MFS transporters; Mdr1 and Flu1; Multidrug resistance (MDR); Pathogenic Candida species; Phylogenetic and gene neighbourhood analyses.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics*
ATP-Binding Cassette Transporters / genetics*
Candida / classification
Candida / genetics*
Drug Resistance, Multiple / genetics*
Evolution, Molecular*
Fungal Proteins / genetics*
Phylogeny*
Synteny*

Substances

ATP Binding Cassette Transporter, Subfamily B, Member 1
ATP-Binding Cassette Transporters
FLU1 protein, Candida albicans
Fungal Proteins