scholarly journals ABC Transporters and Azole Susceptibility in Laboratory Strains of the Wheat Pathogen Mycosphaerella graminicola

2002 ◽  
Vol 46 (12) ◽  
pp. 3900-3906 ◽  
Author(s):  
Lute-Harm Zwiers ◽  
Ioannis Stergiopoulos ◽  
Johannes G. M. Van Nistelrooy ◽  
Maarten A. De Waard
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Abc Transporter ◽  
Abc Transporters ◽  
Rhodamine 6G ◽  
Laboratory Strain ◽  
Mycosphaerella Graminicola ◽  
Cross Resistance ◽  
Wild Type ◽  
Wild Type Level ◽  
Abc Transporter Genes

ABSTRACT Laboratory strains of Mycosphaerella graminicola with decreased susceptibilities to the azole antifungal agent cyproconazole showed a multidrug resistance phenotype by exhibiting cross-resistance to an unrelated chemical, cycloheximide or rhodamine 6G, or both. Decreased azole susceptibility was found to be associated with either decreased or increased levels of accumulation of cyproconazole. No specific relationship could be observed between azole susceptibility and the expression of ATP-binding cassette (ABC) transporter genes MgAtr1 to MgAtr5 and the sterol P450 14α-demethylase gene, CYP51. ABC transporter MgAtr1 was identified as a determinant in azole susceptibility since heterologous expression of the protein reduced the azole susceptibility of Saccharomyces cerevisiae and disruption of MgAtr1 in one specific M. graminicola laboratory strain with constitutive MgAtr1 overexpression restored the level of susceptibility to cyproconazole to wild-type levels. However, the level of accumulation in the mutant with an MgAtr1 disruption did not revert to the wild-type level. We propose that variations in azole susceptibility in laboratory strains of M. graminicola are mediated by multiple mechanisms.

scholarly journals Insecticide Exposure Triggers a Modulated Expression of ABC Transporter Genes in Larvae of Anopheles gambiae s.s.

Insects ◽  
2019 ◽  
Vol 10 (3) ◽  
pp. 66 ◽  
Author(s):  
Valentina Mastrantonio ◽  
Marco Ferrari ◽  
Agata Negri ◽  
Tommaso Sturmo ◽  
Guido Favia ◽  
...  
Keyword(s):  
Anopheles Gambiae ◽  
Abc Transporter ◽  
Abc Transporters ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Larval Mortality ◽  
Expression Patterns ◽  
Main Tool ◽  
Gene Expression Response ◽  
Abc Transporter Genes

Insecticides remain a main tool for the control of arthropod vectors. The urgency to prevent the insurgence of insecticide resistance and the perspective to find new target sites, for the development of novel molecules, are fuelling the study of the molecular mechanisms involved in insect defence against xenobiotic compounds. In this study, we have investigated if ATP-binding cassette (ABC) transporters, a major component of the defensome machinery, are involved in defence against the insecticide permethrin, in susceptible larvae of the malaria vector Anopheles gambiae sensu stricto. Bioassays were performed with permethrin alone, or in combination with an ABC transporter inhibitor. Then we have investigated the expression profiles of five ABC transporter genes at different time points following permethrin exposure, to assess their expression patterns across time. The inhibition of ABC transporters increased the larval mortality by about 15-fold. Likewise, three genes were up-regulated after exposure to permethrin, showing different patterns of expression across the 48 h. Our results provide the first evidences of ABC transporters involvement in defence against a toxic in larvae of An. gambiae s.s. and show that the gene expression response is modulated across time, being continuous, but stronger at the earliest and latest times after exposure.

ABCChips as New Diagnostic Tool to Monitoring Multidrug Resistance in Human Tumor Cells to Chemotherapeutics Agents by Expression Profiling of ATP-Binding Cassette Transporter Genes.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4360-4360
Author(s):  
Jean-Pierre Gillet ◽  
Thomas Efferth ◽  
Damiel Steinbach ◽  
Françoise de Longueville ◽  
Vincent Bertholet ◽  
...  
Keyword(s):  
Cell Lines ◽  
Abc Transporter ◽  
Abc Transporters ◽  
Diagnostic Tool ◽  
Human Tumor ◽  
Multidrug Resistant ◽  
Parental Cell ◽  
Hybridization Experiment ◽  
Low Density ◽  
Abc Transporter Genes

Abstract A major problem in the treatment of tumors represents the development of resistance to chemotherapy. Many mechanisms are responsible for the failure of treatment, the main one being the activation of the ABC transporters. In the present investigation, we developed a low density DNA microarray which contains 38 ABC transporter genes. This tool has been validated with three different characterized multidrug-resistant sublines (CEM/ADR5000, HL60/AR, MCF7-CH1000) and their corresponding drug-sensitive parental cell lines (CCRF-CEM, HL60, MCF7). The multidrug-resistant cell lines used are known to overexpress either the MDR1, MRP1, or BCRP genes. Interestingly, we found not only the overexpression of these genes but also of other ABC transporter genes by using low density microarrays. These results were corroborated by quantitative real time RT-PCR. The microarray allowed the determination of the expression profile of ABC transporters in a single hybridization experiment and may, hence harbor the potential as diagnostic tool to detect drug resistance in the clinic.

scholarly journals ATP-Binding Cassette (ABC) Transporter Genes Involved in Pyrethroid Resistance in the Malaria Vector Anopheles sinensis: Genome-Wide Identification, Characteristics, Phylogenetics, and Expression Profile

2019 ◽  
Vol 20 (6) ◽  
pp. 1409 ◽  
Author(s):  
Qiyi He ◽  
Zhentian Yan ◽  
Fengling Si ◽  
Yong Zhou ◽  
Wenbo Fu ◽  
...  
Keyword(s):  
Abc Transporter ◽  
Abc Transporters ◽  
Pyrethroid Resistance ◽  
Expression Profiles ◽  
Anopheles Sinensis ◽  
Atp Binding ◽  
Rna Seq ◽  
Transporter Family ◽  
Abc Transporter Genes ◽  
Atp Binding Cassette

background: The ATP-binding cassette (ABC) transporters family is one of the largest families of membrane proteins existing in all living organisms. Pyrethroid resistance has become the largest unique obstacle for mosquito control worldwide. ABC transporters are thought to be associated with pyrethroid resistance in some agricultural pests, but little information is known for mosquitoes. Herein, we investigated the diversity, location, characteristics, phylogenetics, and evolution of ABC transporter family of genes in the Anopheles sinensis genome, and identified the ABC transporter genes associated with pyrethroid resistance through expression profiles using RNA-seq and qPCR. Results: 61 ABC transporter genes are identified and divided into eight subfamilies (ABCA-H), located on 22 different scaffolds. Phylogenetic and evolution analyses with ABC transporters of A. gambiae, Drosophila melanogaster, and Homo sapiens suggest that the ABCD, ABCG, and ABCH subfamilies are monophyly, and that the ABCC and ABCG subfamilies have experienced a gene duplication event. Both RNA-seq and qPCR analyses show that the AsABCG28 gene is uniquely significantly upregulated gene in all three field pyrethroid-resistant populations (Anhui, Chongqing, and Yunnan provinces) in comparison with a laboratory-susceptible strain from Jiangsu province. The AsABCG28 is significantly upregulated at 12-h and 24-h after deltamethrin exposure in three-day-old female adults. Conclusion: This study provides the information frame for ABC transporter subfamily of genes, and lays an important basis for the better understanding and further research of ABC transporter function in insecticide toxification. The AsABCG28 gene is associated with pyrethroid detoxification, and it functions at later period in the detoxification process for xenobiotics transportation.

scholarly journals Genome-Wide Identification and Characterization of ABC Transporters in Nine Rosaceae Species Identifying MdABCG28 as a Possible Cytokinin Transporter linked to Dwarfing

2019 ◽  
Vol 20 (22) ◽  
pp. 5783
Author(s):  
Yi Feng ◽  
Qiran Sun ◽  
Guifen Zhang ◽  
Ting Wu ◽  
Xinzhong Zhang ◽  
...  
Keyword(s):  
Abc Transporter ◽  
Abc Transporters ◽  
Prunus Persica ◽  
Prunus Avium ◽  
Structural Features ◽  
Apple Rootstocks ◽  
Specific Expression ◽  
Protein Motifs ◽  
Rosaceae Species ◽  
Abc Transporter Genes

ATP-binding cassette (ABC) transporters constitute a large, diverse, and ubiquitous superfamily that is involved in a broad range of processes. The completion of genome sequencing provides an opportunity to understand the phylogenetic history of the ABC transporter superfamily among Rosaceae species. This study identified a total of 1323 ABC transporter genes from nine Rosaceae genomes: 191 from Malus domestica, 174 from Pyrus communis, 138 from Prunus persica, 118 from Prunus avium, 141 from Prunus dulcis, 122 from Fragaria vesca, 98 from Rubus occidentalis, 162 from Prunus mume, and 179 from Rosa chinensis. Their chemical characterization, phylogenetic analysis, chromosomal localization, gene structure, gene duplication, and tissue-specific expression were studied. Their subcellular localization, transmembrane structures, and protein motifs were predicted. All the ABC transporter genes were grouped into eight subfamilies on the basis of their phylogenetic relationships and structural features. Furthermore, cis-element and expression analysis of 10 potential phytohormone transporters in MdABCG subfamily genes were also performed. Loss of the W-box in the promoter region of MdABCG28 was found to reduce the gene expression level and was linked to the dwarfing phenotype in apple rootstocks. MdABCG28 overexpression promoted shoot growth of atabcg14 mutants in Arabidopsis.

Selective Expression of a Number of ABC Transporter Genes in Normal CD34+CD38− Versus CD34+CD38− Cells, with a Reverse Pattern in a Subgroup of AML Patients.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4291-4291
Author(s):  
Dorina M. van der Kolk ◽  
Susan D.P.W.M. Peeters ◽  
Gerald de Haan ◽  
Leonid Bystrykh ◽  
Elisabeth G.E. de Vries ◽  
...  
Keyword(s):  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Mrna Expression ◽  
Abc Transporter ◽  
Abc Transporters ◽  
Cholesterol Synthesis ◽  
Leukemic Stem Cells ◽  
Hematopoietic Stem ◽  
Reverse Pattern ◽  
Abc Transporter Genes

Abstract Several ABC transporters involved in drug transport have been identified in hematopoietic stem cells, including ABCB1, ABCC1 and ABCG2. The ABC transporters play a role in chemotherapy resistant AML, although the relevant information is mostly obtained from the total AML cell population instead of the leukemic stem cells characterized by the CD34+CD38− phenotype. In this study we investigated which ABC transporters are selectively expressed in normal CD34+CD38− hematopoietic stem cells versus CD34+CD38+ cells, and to what extent lineage-restricted modulation is aberrantly regulated in AML stem cells. We first investigated murine microarray expression data of 29 ABC transporter genes in lin−sca-1+c-kit+ cells (available on www.webqtl.org). Based on these data 7 of the 29 ABC transporters were selected with a high expression profile (abcg1, abcb2, abca2, abcd1, abcc3, abcc5, and abcg2). Based on data published at www.sciencemag.org/cgi/content/full/1073823/DC1, concerning the lineage restricted expression of genes in lin−AA4.1+ + c-kit+sca-1+ murine stem cells, 6 additional stem cell-related ABC transporters (abcb1, abcb11, abcc1b, abcd4, abce1 and abcf2) were selected. The mRNA expression of the 13 ABC transporters was analyzed in the CD34+CD38− versus CD34+CD38+ fraction of human normal bone marrow cells (n=10) by quantitative RT-PCR. Five ABC transporter genes were not detectable in the human CD34+CD38− and CD34+CD38+cells (ABCA2, ABCB11, ABCC3, ABCD1 and ABCF2). Three ABC transporters were expressed equally in both fractions (ABCC5, ABCE1 and ABCG2). However, five ABC transporters were differentially expressed, with a higher expression in the CD34+CD38− cells, (ABCB1, ratio of CD34+CD38+/CD34+CD38− expression of 0.22, p<0.001; ABCG1, 0.27, p<0.001; ABCC1, 0.52, p<0.001; ABCD4, 0.60, p<0.001; and ABCB2, 0.71, p<0.02). Additionally these five ABC transporters were studied in sorted AML subpopulations (n=7). In the sorted AML cells (CD34+CD38− versus CD34+CD38+) a more heterogeneous expression pattern was observed as compared to normal CD34+CD38− cells. In general, the expression levels of ABCB1 and ABCC1 in the AML subpopulations were lower than in normal CD34+CD38− cells, ABCB2 expression was higher in the AML fractions and ABCG1 and ABCD4 were expressed similar in AML and normal CD34+CD38− cells. Downregulation of the ABC transporters in the leukemic CD34+CD38+ cells was observed in 50%–60% of the samples, the reverse pattern was observed for the remaining cases, independent of FAB classification. Since ABCG1 plays a prominent role in cholesterol transport and was strongly downregulated in normal CD34+CD38+ cells (ratio 0.27, p<0.001), the mRNA expression of a number of additional cholesterol synthesis genes was investigated. PPARβ, LXRα and HMCGCoA reductase appeared to be downregulated in the CD34+CD38+ cells (ratios of 0.59, p=0.002, 0.32, p<0.001 and 0.59, p= 0.002 respectively). In conclusion, these results indicate that cholesterol synthesis and transport might play an important role in hematopoietic stem cells. Furthermore, a number of ABC transporter genes appeared to be predominantly expressed in hematopoietic stem cells, and are downregulated upon maturation, whereas the reverse pattern is observed in about 40% of the AML patients suggesting that these more committed leukemic cells might have gained some properties of the leukemic stem cells.

scholarly journals A mutation allowing an mRNA secondary structure diminishes translation of Saccharomyces cerevisiae iso-1-cytochrome c.

1985 ◽  
Vol 5 (8) ◽  
pp. 1839-1846 ◽  
Author(s):  
S B Baim ◽  
D F Pietras ◽  
D C Eustice ◽  
F Sherman
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Amino Acid ◽  
Secondary Structure ◽  
Cytochrome C ◽  
Mrna Secondary Structure ◽  
Wild Type ◽  
Stable Secondary Structure ◽  
Yeast Saccharomyces Cerevisiae ◽  
Wild Type Level ◽  
Altered Protein

The CYC1-239-O mutation in the yeast Saccharomyces cerevisiae produces a -His-Leu- replacement of the normal -Ala-Gly- sequence at amino acid positions 5 and 6, which lie within a dispensable region of iso-1-cytochrome c; this mutation can accommodate the formation of a hairpin structure at the corresponding site in the mRNA. The amount of the altered protein was diminished to 20% of the wild-type level, whereas the amount of the mRNA remained normal. However, in contrast to the normal CYC1+ mRNA that is associated mainly with four to seven ribosomes, the bulk of the CYC1-239-O mRNA is associated with one to four ribosomes. These results suggest that the stable secondary structure within the translated region of the CYC1 mRNA diminishes translation by inhibiting elongation.

scholarly journals TAC1, Transcriptional Activator of CDR Genes, Is a New Transcription Factor Involved in the Regulation of Candida albicans ABC Transporters CDR1 and CDR2

2004 ◽  
Vol 3 (6) ◽  
pp. 1639-1652 ◽  
Author(s):  
Alix T. Coste ◽  
Mahir Karababa ◽  
Françoise Ischer ◽  
Jacques Bille ◽  
Dominique Sanglard
Keyword(s):  
Transcription Factor ◽  
Candida Albicans ◽  
Abc Transporters ◽  
Transcriptional Activator ◽  
Laboratory Strain ◽  
Azole Resistance ◽  
Transcriptional Activators ◽  
Genes Encoding ◽  
Responsive Element ◽  
Abc Transporter Genes

ABSTRACT The ABC transporter genes CDR1 and CDR2 can be upregulated in Candida albicans developing resistance to azoles or can be upregulated by exposing cells transiently to drugs such as fluphenazine. The cis-acting drug-responsive element (DRE) present in the promoters of both genes and necessary for their upregulation contains 5′-CGG-3′ triplets that are often recognized by transcriptional activators with Zn(2)-Cys(6) fingers. In order to isolate regulators of CDR1 and CDR2, the C. albicans genome was searched for genes encoding proteins with Zn(2)-Cys(6) fingers. Interestingly, three of these genes were tandemly arranged near the mating locus. Their involvement in CDR1 and CDR2 upregulation was addressed because a previous study demonstrated a link between mating locus homozygosity and azole resistance. The deletion of only one of these genes (orf19.3188) was sufficient to result in a loss of transient CDR1 and CDR2 upregulation by fluphenazine and was therefore named TAC1 (transcriptional activator of CDR genes). Tac1p has a nuclear localization, and a fusion of Tac1p with glutathione S-transferase could bind the cis-acting regulatory DRE in both the CDR1 and the CDR2 promoters. TAC1 is also relevant for azole resistance, since a TAC1 allele (TAC1-2) recovered from an azole-resistant strain could trigger constitutive upregulation of CDR1 and CDR2 in an azole-susceptible laboratory strain. Transcript profiling experiments performed with a TAC1 mutant and a revertant containing TAC1-2 revealed not only CDR1 and CDR2 as targets of TAC1 regulation but also other genes (RTA3, IFU5, and HSP12) that interestingly contained a DRE-like element in their promoters. In conclusion, TAC1 appears to be the first C. albicans transcription factor involved in the control of genes mediating antifungal resistance.

scholarly journals ABC-transporter upregulation mediates resistance to the CDK7 inhibitors THZ1 and ICEC0942

Oncogene ◽  
2019 ◽  
Vol 39 (3) ◽  
pp. 651-663 ◽  
Author(s):  
Georgina P. Sava ◽  
Hailing Fan ◽  
Rosemary A. Fisher ◽  
Sabrina Lusvarghi ◽  
Sunil Pancholi ◽  
...  
Keyword(s):  
Cell Lines ◽  
Abc Transporter ◽  
Abc Transporters ◽  
Cancer Therapeutics ◽  
Resistant Cell ◽  
Cross Resistance ◽  
Common Mechanism ◽  
Mechanism Of Resistance ◽  
Resistant Lines ◽  
Resistant Cells

Abstract The CDK7 inhibitors (CDK7i) ICEC0942 and THZ1, are promising new cancer therapeutics. Resistance to targeted drugs frequently compromises cancer treatment. We sought to identify mechanisms by which cancer cells may become resistant to CDK7i. Resistant lines were established through continuous drug selection. ABC-transporter copy number, expression and activity were examined using real-time PCR, immunoblotting and flow cytometry. Drug responses were measured using growth assays. ABCB1 was upregulated in ICEC0942-resistant cells and there was cross-resistance to THZ1. THZ1-resistant cells upregulated ABCG2 but remained sensitive to ICEC0942. Drug resistance in both cell lines was reversible upon inhibition of ABC-transporters. CDK7i response was altered in adriamycin- and mitoxantrone-resistant cell lines demonstrating ABC-transporter upregulation. ABCB1 expression correlated with ICEC0942 and THZ1 response, and ABCG2 expression with THZ2 response, in a panel of cancer cell lines. We have identified ABCB1 upregulation as a common mechanism of resistance to ICEC0942 and THZ1, and confirmed that ABCG2 upregulation is a mechanism of resistance to THZ1. The identification of potential mechanisms of CDK7i resistance and differences in susceptibility of ICEC0942 and THZ1 to ABC-transporters, may help guide their future clinical use.

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