Biomedical subjects

Elie Dassa

Publications and source records attributed to Elie Dassa.

8 recordsLinked to original sources

PubMed2006

The identification and evaluation of ATP binding cassette systems in the intracellular bacterium Francisella tularensis.

Francisella tularensis is a facultative intracellular bacterium responsible for the disease tularemia. Analysis of the fully sequenced genome of the virulent F. tularensis strain SCHU S4 has led to the identification of twenty ATP binding cassette (ABC) systems, of which five appear to be non-functional. The fifteen complete systems comprise three importers, five exporters, four systems involved in non-transport processes, and three systems of unknown or ill-defined function. The number and classification of the ABC systems in F. tularensis is similar to that observed in other intracellular bacteria, indicating that some of these systems may be important for the intracellular lifestyle of these organisms. Among the ABC systems identified in the genome are systems that may be involved in the virulence of F. tularensis SCHU S4. Six ABC system proteins were evaluated as candidate vaccine antigens against tularemia, although none provided significant protection against F. tularensis. However, a greater understanding of these systems may lead to the development of countermeasures against F. tularensis.

ATP-Binding Cassette Transporters↗

PubMed2006

ATP hydrolysis is essential for the function of the Uup ATP-binding cassette ATPase in precise excision of transposons.

In Escherichia coli K-12, the RecA- and transposase-independent precise excision of transposons is thought to be mediated by the slippage of the DNA polymerase between the two short direct repeats that flank the transposon. Inactivation of the uup gene, encoding an ATP-binding cassette (ABC) ATPase, led to an important increase in the frequency of precise excision of transposons Tn10 and Tn5 and a defective growth of bacteriophage Mu. To provide insight into the mechanism of Uup in transposon excision, we purified this protein, and we demonstrated that it is a cytosolic ABC protein. Purified recombinant Uup binds and hydrolyzes ATP and undergoes a large conformational change in the presence of this nucleotide. This change affects a carboxyl-terminal domain of the protein that displays predicted structural homology with the socalled little finger domain of Y family DNA polymerases. In these enzymes, this domain is involved in DNA binding and in the processivity of replication. We show that Uup binds to DNA and that this binding is in part dependent on its carboxyl-terminal domain. Analysis of Walker motif B mutants suggests that ATP hydrolysis at the two ABC domains is strictly coordinated and is essential for the function of Uup in vivo.

ATP-Binding Cassette Transporters↗

PubMed2005

Molecular analysis of resistance to streptogramin A compounds conferred by the Vga proteins of staphylococci.

The Vga and Msr resistance determinants, encoded by mobile genetic elements in various staphylococcal strains, belong to a family of ATP-binding cassette (ABC) proteins whose functions and structures are ill defined. Their amino acid sequences are similar to those of proteins involved in the immunity of streptomycetes to the macrolide-lincosamide-streptogramin antibiotics that they produce. Sequence analysis of the genomes of the gram-positive bacteria with low G+C contents revealed that Lmo0919 from Listeria monocytogenes is more closely related to Vga variants than to Msr variants. In the present study we compared the antibiotic resistance profiles conferred by the Vga-like proteins in two staphylococcal hosts. It was shown that Vga(A), the Vga(A) variant [Vga(A)v], and Lmo0919 can confer resistance to lincosamides and streptogramin A compounds, while only Vga(B) is able to increase the level of resistance to pristinamycin, a mixture of streptogramin A and streptogramin B compounds. By using polyclonal antibodies, we found that the Vga(A) protein colocalized with the beta subunit of the F(1)-F(0) ATPase in the membrane fractions of staphylococcal cells. In order to identify functional units in these atypical ABC proteins, such as regions that might be involved in substrate specificity and/or membrane targeting, we analyzed the resistance phenotypes conferred by various plasmids carrying parts or modified versions of the vga(A) gene and we determined the subcellular localization of the gene products. Only polypeptides composed of two ABC domains were detected in the cell membranes. No region of drug specificity was identified. Resistance properties were dependent on the integrities of both Walker B motifs.

ATP-Binding Cassette Transporters↗

PubMed2004

Inventory and comparative analysis of rice and Arabidopsis ATP-binding cassette (ABC) systems.

ATP-binding cassette (ABC) proteins constitute a large superfamily found in all kingdoms of living organisms. The recent completion of two draft sequences of the rice (Oryza sativa) genome allowed us to analyze and classify its ABC proteins and to compare to those in Arabidopsis thaliana. We identified a similar number of ABC proteins in rice and Arabidopsis (121 versus 120), despite the rice genome being more than three times the size of Arabidopsis. Both Arabidopsis and rice have representative members in all seven major subfamilies of ABC ATPases (A to G) commonly found in eukaryotes. This comparative analysis allowed the detection of 29 potential orthologous sequences in Arabidopsis and rice. However, plant share with prokaryotes a specific set of ABC systems that is not detected in animals. These ABC systems might be inherited from the cyanobacterial ancestor of chloroplasts. The present work provides the first complete inventory of rice ABC proteins and an updated inventory of those proteins in Arabidopsis.

ATP-Binding Cassette Transporters↗

PubMed2004

The metNPQ operon of Bacillus subtilis encodes an ABC permease transporting methionine sulfoxide, D- and L-methionine.

The Bacillus subtilis yusCBA operon, which encodes an ABC-type transporter, contains an S-box motif in its promoter region. We showed that the expression of these genes is repressed via the S-box system when methionine is available. The YusCB proteins are involved in the transport of both d- and l-methionine but also methionine sulfoxide. A yusCB mutant is unable to grow in the presence of 5 microM l-methionine or 100 microM methionine sulfoxide, while it grows similarly to the wild type with 100 microM l-methionine and 1 mM methionine sulfoxide. Other uptake systems are therefore present for these two compounds. In contrast, the Yus ABC transporter corresponds to the sole d-methionine uptake system. We propose to rename yusC, yusB and yusA as metN, metP and metQ, respectively.

ATP-Binding Cassette Transporters↗

PubMed2003

The genome sequence of the entomopathogenic bacterium Photorhabdus luminescens.

Photorhabdus luminescens is a symbiont of nematodes and a broad-spectrum insect pathogen. The complete genome sequence of strain TT01 is 5,688,987 base pairs (bp) long and contains 4,839 predicted protein-coding genes. Strikingly, it encodes a large number of adhesins, toxins, hemolysins, proteases and lipases, and contains a wide array of antibiotic synthesizing genes. These proteins are likely to play a role in the elimination of competitors, host colonization, invasion and bioconversion of the insect cadaver, making P. luminescens a promising model for the study of symbiosis and host-pathogen interactions. Comparison with the genomes of related bacteria reveals the acquisition of virulence factors by extensive horizontal transfer and provides clues about the evolution of an insect pathogen. Moreover, newly identified insecticidal proteins may be effective alternatives for the control of insect pests.

Amino Acid Sequence↗

PubMed2002

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

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.

ATP-Binding Cassette Transporters↗

PubMed2002

Phylogenetic and functional classification of ATP-binding cassette (ABC) systems.

ATP binding cassette (ABC) systems constitute one of the most abundant superfamilies of proteins. They are involved in the transport of a wide variety of substances, but also in many cellular processes and in their regulation. In this paper, we made a comparative analysis of the properties of ABC systems and we provide a phylogenetic and functional classification. This analysis will be helpful to accurately annotate ABC systems discovered during the sequencing of the genome of living organisms and to identify the partners of the ABC ATPases.

ATP-Binding Cassette Transporters↗