The Bacillus subtilis yts, yxd and yvc gene clusters encode a putative ABC transporter and a functionally coupled two-component system. When tested for their sensitivity towards a series of antibiotics, null yts mutants were found to be sensitive to bacitracin. Real-time polymerase chain reaction (PCR) experiments demonstrated that the presence of bacitracin in the growth medium strongly stimul...

BACKGROUND Multidrug resistance, a major impediment to successful cancer chemotherapy, is the result of overexpression of ATP-binding cassette (ABC) transporters extruding internalized drugs. Silencing of ABC transporter gene expression with small interfering RNA (siRNA) could be an attractive approach to overcome multidrug resistance of cancer, although delivery of siRNA remains a major hurdle...

The bacterial uptake of steroids and their metabolites remains poorly understood. We investigated two transporters associated with cholate catabolism in Rhodococcus jostii RHA1. Reverse transcriptase quantitative-PCR indicated that an ATP-binding cassette (ABC) transporter and a major facilitator superfamily (MFS) transporter were upregulated 16.7- and 174-fold, respectively, during the exponen...

ATP-binding cassette (ABC) transporters make up a superfamily of transmembrane proteins that play a critical role in the development of drug resistance. This phenomenon is especially important in oncology, where superfamily member ABCG2 (also called BCRP - breast cancer resistance protein) is known to interact with dozens of anti-cancer agents that are ABCG2 substrates. In addition to the well-...

Parasitic flatworms of the genus Schistosoma cause schistosomiasis, a neglected tropical disease that affects hundreds of millions. Treatment of schistosomiasis depends almost entirely on the drug praziquantel (PZQ). Though essential to treating and controlling schistosomiasis, a major limitation of PZQ is that it is not active against immature mammalian-stage schistosomes. Furthermore, there a...

The concept that the cystic fibrosis (CF) transmembrane conductance regulator, the protein product of the CF gene, can conduct larger multivalent anions such as ATP as well as Cl- is controversial. In this review, I examine briefly past findings that resulted in controversy. It is not the goal of this review to revisit these disparate findings in detail. Rather, I focus intently on more recent ...

The maltose transport complex of E.coli is one of the most well-characterized members of the ATP-Binding Cassette (ABC) protein superfamily. ABC proteins represent the largest superfamily of transmembrane proteins in prokaryotes and eukaryotes, performing diverse functions from ion transport by the cystic fibrosis transmembrane regulator to multiple drug efflux by the P-glycoprotein transporter...

High gene transfer efficiencies have been difficult to achieve in hematopoietic progenitor cells (HPCs) but are important to therapeutic success of HPC gene therapy. Efficient gene transfer is especially challenging with use of column-purified vector for clinical application, as opposed to centrifuged vector commonly used for research. We investigated novel approaches to increase transduction b...

Nonsynonymous single nucleotide polymorphisms (nsSNPs) in coding regions that can lead to amino acid changes may cause alteration of protein function and account for susceptibility to disease and altered drug/xenobiotic response. Abundant nsSNPs have been found in genes coding for human ATP-binding cassette (ABC) transporters, but there is little known about the relationship between the genotyp...

Drug resistance (DR) is the major limiting factor in the successful treatment of systemic neoplasia with cytotoxic chemotherapy. DR can be either intrinsic or acquired, and although the development and clinical implications are different, the underlying mechanisms are likely to be similar. Most causes for DR are pharmacodynamic in nature, result from adaptations within the tumor cell and includ...