Comparative analysis of sequences encoding ABC systems in the genome of the microsporidian Encephalitozoon cuniculi

Abstract

Microsporidia are amitochondriate eukaryotic microbes with fungal affinities and a common status of obligate intracellular parasites. A set of 13 potential genes encoding ATP-binding cassette (ABC) systems was identified in the fully sequenced genome of Encephalitozoon cuniculi. Our analyses of multiple alignments, phylogenetic trees and conserved motifs support a distribution of E. cuniculi ABC systems within only four subfamilies. Six half transporters are homologous to the yeast ATM1 mitochondrial protein, a finding which is in agreement with the hypothesis of a cryptic mitochondrion-derived compartment playing a role in the synthesis and transport of Fe^S clusters. Five half transporters are similar to the human ABCG1 and ABCG2 proteins, involved in regulation of lipid trafficking and anthracyclin resistance respectively. Two proteins with duplicated ABC domains are clearly candidate to non-transport ABC systems: the first is homologous to mammalian RNase L inhibitor and the second to the yeast translation initiation regulator GCN20. An unusual feature of ABC systems in E. cuniculi is the lack of homologs of P-glycoprotein and other ABC transporters which are involved in multiple drug resistance in a large number of eukaryotic microorganisms. ß

The parasitophorous vacuole of Encephalitozoon cuniculi: Biogenesis and characteristics of the host cell–pathogen interface

“…E. cuniculi possesses various transmembrane transporters, among them 13 putative ABC transporters of unknown substrate specificity (Katinka et al, 2001;Cornillot et al, 2002;Williams, 2009). Most intracellular eukaryotic pathogens are deficient in de novo purine synthesis, but retained de novo pyrimidine synthesis.…”

Opportunistic Infections: Toxoplasma, Sarcocystis, and Microsporidia

“…Twelve different ABC proteins encoded by 13 genes (two identical copies on chromosome I) are indeed representative of only four subfamilies and none of these is organized as a "full-size" ABC transporter, i.e. comprising two membrane spanning domains (IM) and two cytoplasmic ATPase domains (ABC) (Cornillot et al, 2002). Five "half-size" ABC transporters sharing an ABC-IM topology were assigned to the WHI subfamily, suggesting a participation to sterol and phospholipid transport and/or to drug resistance if referring to the functions allocated to some human homologs (review: Dean et al, 2001).…”

“…Two distinct sequences for ABC transporters (EiABC1 and EiABC2) have been reported in E. intestinalis (Bonafonte et al, 2001). EiABC1 appears as the ortholog of one E. cuniculi HMT protein (ECU03_0240) (Cornillot et al, 2002). By contrast, EiABC2 that was assumed to represent a multi-drug resistance pump (Bonafonte et al, 2001) has no clear counterpart in E. cuniculi (Cornillot et al, 2002).…”

“…EiABC1 appears as the ortholog of one E. cuniculi HMT protein (ECU03_0240) (Cornillot et al, 2002). By contrast, EiABC2 that was assumed to represent a multi-drug resistance pump (Bonafonte et al, 2001) has no clear counterpart in E. cuniculi (Cornillot et al, 2002). Its domain organization is of IM-ABC type, however.…”

“…This case of high intrageneric divergence as well as the lack of potential mitochondrial targeting signal in both EiABC2 and two E. cuniculi HMT proteins strongly argue against a mitosomal location and, therefore, offer a large choice of putative transport functions to be explored. The two remaining ABC systems of E. cuniculi lack transmembrane domain (ABC-ABC type) and correspond to two wellconserved proteins that are respectively homologous to human RNase L inhibitor (RLI) and yeast translational regulator GCN20 (Cornillot et al, 2002). The function of non-mammalian RLI proteins is unknown.…”