scholarly journals The ATP-Binding Cassette (ABC) Transport Systems in Mycobacterium tuberculosis: Structure, Function, and Possible Targets for Therapeutics

Biology ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 443
Author(s):  
Marcelo Cassio Barreto de Oliveira ◽  
Andrea Balan
Keyword(s):  
Drug Resistance ◽  
Mycobacterium Tuberculosis ◽  
Abc Transporters ◽  
Nutrient Recycling ◽  
Structural Features ◽  
Transport Systems ◽  
Multiple Drug ◽  
Atp Binding ◽  
Substrate Uptake ◽  
Atp Binding Cassette

Mycobacterium tuberculosis is the etiological agent of tuberculosis (TB), a disease that affects millions of people in the world and that is associated with several human diseases. The bacillus is highly adapted to infect and survive inside the host, mainly because of its cellular envelope plasticity, which can be modulated to adapt to an unfriendly host environment; to manipulate the host immune response; and to resist therapeutic treatment, increasing in this way the drug resistance of TB. The superfamily of ATP-Binding Cassette (ABC) transporters are integral membrane proteins that include both importers and exporters. Both types share a similar structural organization, yet only importers have a periplasmic substrate-binding domain, which is essential for substrate uptake and transport. ABC transporter-type importers play an important role in the bacillus physiology through the transport of several substrates that will interfere with nutrition, pathogenesis, and virulence. Equally relevant, exporters have been involved in cell detoxification, nutrient recycling, and antibiotics and drug efflux, largely affecting the survival and development of multiple drug-resistant strains. Here, we review known ABC transporters from M. tuberculosis, with particular focus on the diversity of their structural features and relevance in infection and drug resistance.

scholarly journals ATP-binding Cassette Transporters Are Required for Efficient RNA Interference in Caenorhabditis elegans

2006 ◽  
Vol 17 (8) ◽  
pp. 3678-3688 ◽  
Author(s):  
Prema Sundaram ◽  
Benjamin Echalier ◽  
Wang Han ◽  
Dawn Hull ◽  
Lisa Timmons
Keyword(s):  
Rna Interference ◽  
Caenorhabditis Elegans ◽  
Abc Transporters ◽  
Transport Systems ◽  
Atp Binding ◽  
C Elegans ◽  
Steep Concentration Gradient ◽  
Conserved Gene ◽  
Membrane Transport Systems ◽  
Atp Binding Cassette

RNA interference (RNAi) is a conserved gene-silencing phenomenon that can be triggered by delivery of double-stranded RNA (dsRNA) to cells and is a widely exploited technology in analyses of gene function. Although a number of proteins that facilitate RNAi have been identified, current descriptions of RNAi and interrelated mechanisms are far from complete. Here, we report that the Caenorhabditis elegans gene haf-6 is required for efficient RNAi. HAF-6 is a member of the ATP-binding cassette (ABC) transporter gene superfamily. ABC transporters use ATP to translocate small molecule substrates across the membranes in which they reside, often against a steep concentration gradient. Collectively, ABC transporters are involved in a variety of activities, including protective or barrier mechanisms that export drugs or toxins from cells, organellar biogenesis, and mechanisms that protect against viral infection. HAF-6 is expressed predominantly in the intestine and germline and is localized to intracellular reticular organelles. We further demonstrate that eight additional ABC genes from diverse subfamilies are each required for efficient RNAi in C. elegans. Thus, the ability to mount a robust RNAi response to dsRNA depends upon the deployment of two ancient systems that respond to environmental assaults: RNAi mechanisms and membrane transport systems that use ABC proteins.

scholarly journals Contributions of Aspergillus fumigatus ATP-Binding Cassette Transporter Proteins to Drug Resistance and Virulence

2013 ◽  
Vol 12 (12) ◽  
pp. 1619-1628 ◽  
Author(s):  
Sanjoy Paul ◽  
Daniel Diekema ◽  
W. Scott Moye-Rowley
Keyword(s):  
Drug Resistance ◽  
Aspergillus Fumigatus ◽  
Abc Transporter ◽  
Abc Transporters ◽  
Sequence Similarity ◽  
Atp Binding ◽  
Content Type ◽  
Transporter Proteins ◽  
Encoding Genes ◽  
Atp Binding Cassette

ABSTRACTIn yeast cells such as those ofSaccharomyces cerevisiae, expression of ATP-binding cassette (ABC) transporter proteins has been found to be increased and correlates with a concomitant elevation in azole drug resistance. In this study, we investigated the roles of twoAspergillus fumigatusproteins that share high sequence similarity withS. cerevisiaePdr5, an ABC transporter protein that is commonly overproduced in azole-resistant isolates in this yeast. The twoA. fumigatusgenes encoding the ABC transporters sharing the highest sequence similarity toS. cerevisiaePdr5 are calledabcAandabcBhere. We constructed deletion alleles of these two different ABC transporter-encoding genes in three different strains ofA. fumigatus. Loss ofabcBinvariably elicited increased azole susceptibility, whileabcAdisruption alleles had variable phenotypes. Specific antibodies were raised to both AbcA and AbcB proteins. These antisera allowed detection of AbcB in wild-type cells, while AbcA could be visualized only when overproduced from thehspApromoter inA. fumigatus. Overproduction of AbcA also yielded increased azole resistance. Green fluorescent protein fusions were used to provide evidence that both AbcA and AbcB are localized to the plasma membrane inA. fumigatus. Promoter fusions to firefly luciferase suggested that expression of both ABC transporter-encoding genes is inducible by azole challenge. Virulence assays implicated AbcB as a possible factor required for normal pathogenesis. This work provides important new insights into the physiological roles of ABC transporters in this major fungal pathogen.

scholarly journals Overexpression and functional characterization of an ABC (ATP-binding cassette) transporter encoded by the genes drrA and drrB of Mycobacterium tuberculosis

2002 ◽  
Vol 367 (1) ◽  
pp. 279-285 ◽  
Author(s):  
Baisakhee Saha CHOUDHURI ◽  
Sanjib BHAKTA ◽  
Rajib BARIK ◽  
Joyoti BASU ◽  
Manikuntala KUNDU ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Abc Transporters ◽  
Efflux Pump ◽  
Functional Characterization ◽  
Atp Binding ◽  
E Coli ◽  
Neutral Compound ◽  
Genes Encoding ◽  
Simultaneous Expression ◽  
Atp Binding Cassette

The genes encoding ATP-binding cassette (ABC) transporters occupy 2.5% of the genome of Mycobacterium tuberculosis. However, none of these putative ABC transporters has been characterized so far. We describe the development of expression systems for simultaneous expression of the ATP-binding protein DrrA and the membrane integral protein DrrB which together behave as a functional doxorubicin efflux pump. Doxorubicin uptake in Escherichia coli or Mycobacterium smegmatis expressing DrrAB was inhibited by reserpine, an inhibitor of ABC transporters. The localization of DrrA to the membrane depended on the simultaneous expression of DrrB. ATP binding was positively regulated by doxorubicin and daunorubicin. At the same time, DrrB appeared to be sensitive to proteolysis when expressed alone in the absence of DrrA. Simultaneous expression of the two polypeptides was essential to obtain a functional doxorubicin efflux pump. Expression of DrrAB in E. coli conferred 8-fold increased resistance to ethidium bromide, a cationic compound. 2′,7′-bis-(2-Carboxyethyl)-5(6)-carboxyfluorescein (BCECF), a neutral compound, also behaved as a substrate of the reconstituted efflux pump. When expressed in M. smegmatis, DrrAB conferred resistance to a number of clinically relevant, structurally unrelated antibiotics. The resistant phenotype could be reversed by verapamil and reserpine, two potent inhibitors of ABC transporters.

Mouse ATP-Binding Cassette (ABC) Transporters Conferring Multi-Drug Resistance

2015 ◽  
Vol 15 (4) ◽  
pp. 423-432 ◽  
Author(s):  
Shuaizhang Li ◽  
Wen Zhang ◽  
Xuejiao Yin ◽  
Shilai Xing ◽  
Heidi Xie ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Abc Transporters ◽  
Multi Drug Resistance ◽  
Atp Binding ◽  
Atp Binding Cassette

scholarly journals An energy-blocking nanoparticle decorated with anti-VEGF antibody to reverse chemotherapeutic drug resistance

RSC Advances ◽  
2019 ◽  
Vol 9 (21) ◽  
pp. 12110-12123 ◽  
Author(s):  
Liu-Qing Gu ◽  
Peng-Fei Cui ◽  
Lei Xing ◽  
Yu-Jing He ◽  
Xin Chang ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Cell Membrane ◽  
Therapeutic Effect ◽  
Abc Transporters ◽  
Multi Drug Resistance ◽  
Atp Binding ◽  
Chemotherapeutic Drugs ◽  
Chemotherapeutic Drug ◽  
Anti Vegf ◽  
Atp Binding Cassette

Multi-drug resistance (MDR) of tumor has greatly hindered the therapeutic effect of chemotherapeutic drugs, resulting in chemotherapy failure, and overexpression of ATP-binding cassette (ABC) transporters in cell membrane is the main cause of MDR.

The Role of ATP-binding Cassette (ABC) Transporters in Bacterial Phytopathogenesis

2020 ◽  
Author(s):  
Yuan Zeng ◽  
Amy O. Charkowski
Keyword(s):  
Abc Transporters ◽  
Plant Pathogens ◽  
Atp Hydrolysis ◽  
Transport Systems ◽  
Atp Binding ◽  
Cell Functions ◽  
Animal Pathogens ◽  
Selective Membrane ◽  
Microbe Interactions ◽  
Atp Binding Cassette

Bacteria use selective membrane transporting strategies to support cell survival in different environments. Of the membrane transport systems, ATP-binding cassette (ABC) transporters, which utilize the energy of ATP hydrolysis to deliver substrate across the cytoplasmic membrane, are the largest and most diverse superfamily. These transporters import nutrients, export substrates, and are required for diverse cell functions, including cell division and morphology, gene regulation, surface motility, chemotaxis, and interspecies competition. Phytobacterial pathogens may encode numerous ABC transporter homologs compared to related non-phytopathogens, with up to 160 transporters per genome, suggesting that plant pathogens must be able to import or respond to a greater number of molecules than saprophytes or animal pathogens. Despite their importance, ABC transporters have been little examined in plant pathogens. And yet, to understand bacterial phytopathogenesis and evolution, we need to understand the roles that ABC transporters play in plant-microbe interactions. In this review, we outline a multitude of roles that bacterial ABC transporters play, using both plant and animal pathogens as examples, to emphasize the importance of exploring these transporters in phytobacteriology.

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