scholarly journals The Putative Response Regulator BaeR Stimulates Multidrug Resistance of Escherichia coli via a Novel Multidrug Exporter System, MdtABC

2002 ◽  
Vol 184 (15) ◽  
pp. 4161-4167 ◽  
Author(s):  
Satoshi Nagakubo ◽  
Kunihiko Nishino ◽  
Takahiro Hirata ◽  
Akihito Yamaguchi
Keyword(s):  
Bile Salts ◽  
Response Regulator ◽  
Multidrug Transporter ◽  
Drug Efflux ◽  
Efflux System ◽  
Membrane Fusion Protein ◽  
Blast Search ◽  
Gram Negative Organisms ◽  
Novobiocin Resistance ◽  
Resistance Spectrum

ABSTRACT Overproduction of the response regulator BaeR confers resistance to novobiocin and bile salts in a ΔacrAB mutant by stimulating drug exporter gene expression. The mdtABC (multidrug transporter ABC, formerly known as yegMNO) genes, which encode a resistance-nodulation-cell division (RND) drug efflux system, are responsible for resistance. The MdtABC system comprises the transmembrane MdtB/MdtC heteromultimer and MdtA membrane fusion protein. MdtAC also confers bile salt, but not novobiocin, resistance. This indicates that the evolution from an MdtC homomultimer to an MdtBC heteromultimer contributed to extend the drug resistance spectrum. A BLAST search suggested that such a heteromultimer-type RND exporter constitutes a unique family among gram-negative organisms.

scholarly journals Multidrug efflux in intrinsic resistance to trimethoprim and sulfamethoxazole in Pseudomonas aeruginosa.

1996 ◽  
Vol 40 (10) ◽  
pp. 2288-2290 ◽  
Author(s):  
T Köhler ◽  
M Kok ◽  
M Michea-Hamzehpour ◽  
P Plesiat ◽  
N Gotoh ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Outer Membrane Proteins ◽  
Multiple Drug ◽  
Drug Efflux ◽  
Wild Type ◽  
Multidrug Efflux ◽  
Efflux System ◽  
Intrinsic Resistance ◽  
Wild Type Parent ◽  
Multidrug Efflux System

Pseudomonas aeruginosa possesses at least two multiple drug efflux systems which are defined by the outer membrane proteins OprM and OprJ. We have found that mutants overexpressing OprM were two- and eightfold more resistant than their wild-type parent to sulfamethoxazole (SMX) and trimethoprim (TMP), respectively. For OprJ-overproducing strains, MICs of TMP increased fourfold but those of SMX were unchanged. Strains overexpressing OprM, but not those overexpressing OprJ, became hypersusceptible to TMP and SMX when oprM was inactivated. The wild-type antibiotic profile could be restored in an oprM mutant by transcomplementation with the cloned oprM gene. These results demonstrate that the mexABoprM multidrug efflux system is mainly responsible for the intrinsic resistance of P. aeruginosa to TMP and SMX.

scholarly journals Fluconazole Resistance Associated with Drug Efflux and Increased Transcription of a Drug Transporter Gene, PDH1, inCandida glabrata

1998 ◽  
Vol 42 (7) ◽  
pp. 1695-1701 ◽  
Author(s):  
Haruko Miyazaki ◽  
Yoshitsugu Miyazaki ◽  
Antonia Geber ◽  
Tanya Parkinson ◽  
Christopher Hitchcock ◽  
...  
Keyword(s):  
Multidrug Transporter ◽  
Drug Efflux ◽  
Drug Transporter ◽  
Transporter Gene ◽  
Fluconazole Resistance ◽  
Binding Domains ◽  
Immunodeficiency Virus ◽  
Susceptible Isolate ◽  
High Doses

ABSTRACT Sequential Candida glabrata isolates were obtained from the mouth of a patient infected with human immunodeficiency virus type 1 who was receiving high doses of fluconazole for oropharyngeal thrush. Fluconazole-susceptible colonies were replaced by resistant colonies that exhibited both increased fluconazole efflux and increased transcripts of a gene which codes for a protein with 72.5% identity to Pdr5p, an ABC multidrug transporter in Saccharomyces cerevisiae. The deduced protein had a molecular mass of 175 kDa and was composed of two homologous halves, each with six putative transmembrane domains and highly conserved sequences of ATP-binding domains. When the earliest and most azole-susceptible isolate of C. glabrata from this patient was exposed to fluconazole, increased transcripts of thePDR5 homolog appeared, linking azole exposure to regulation of this gene.

scholarly journals CSIG-32. DUAL PI3K/Akt INHIBITION TO OVERCOME THE P-gp/BCRP DRUG EFFLUX SYSTEM FOR IMPROVED DRUG DELIVERY IN GLIOBLASTOMA THERAPY

2018 ◽  
Vol 20 (suppl_6) ◽  
pp. vi50-vi50
Author(s):  
Anika Hartz ◽  
Julia Schulz ◽  
Brent Sokola ◽  
Bjoern Bauer
Keyword(s):  
Drug Delivery ◽  
Drug Efflux ◽  
Efflux System

Ciprofloxacin resistance by altered gyrase and drug efflux system inPseudomonas aeruginosa

1995 ◽  
Vol 18 (3) ◽  
pp. 173-178 ◽  
Author(s):  
Myungsun Cho ◽  
Doyeob Kim ◽  
Jae Yang Kong ◽  
Sung-II Yang
Keyword(s):  
Drug Efflux ◽  
Efflux System ◽  
Ciprofloxacin Resistance

scholarly journals Crystal Structure of the Membrane Fusion Protein, MexA, of the Multidrug Transporter inPseudomonas aeruginosa

2004 ◽  
Vol 279 (25) ◽  
pp. 25939-25942 ◽  
Author(s):  
Hiroyuki Akama ◽  
Takanori Matsuura ◽  
Sachiko Kashiwagi ◽  
Hiroshi Yoneyama ◽  
Shin-ichiro Narita ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Fusion Protein ◽  
Membrane Fusion ◽  
Multidrug Transporter ◽  
Membrane Fusion Protein

scholarly journals A subset of virus-specific CD161+ T cells selectively express the multidrug transporter MDR1 and are resistant to chemotherapy in AML

Blood ◽  
2017 ◽  
Vol 129 (6) ◽  
pp. 740-758 ◽  
Author(s):  
Abdullah Alsuliman ◽  
Muharrem Muftuoglu ◽  
Ahmad Khoder ◽  
Yong-Oon Ahn ◽  
Rafet Basar ◽  
...  
Keyword(s):  
T Cells ◽  
Multidrug Transporter ◽  
Drug Efflux ◽  
Key Points

Key Points Human CD4+CD161+ T cells display unique properties including MDR1-mediated drug efflux capacity and quiescence. CD4+CD161+ T cells are enriched within the long-lived viral-specific Th1 memory repertoire in humans.

scholarly journals Abcc4 Together with Abcb1 and Abcg2 Form a Robust Cooperative Drug Efflux System That Restricts the Brain Entry of Camptothecin Analogues

2013 ◽  
Vol 19 (8) ◽  
pp. 2084-2095 ◽  
Author(s):  
Fan Lin ◽  
Serena Marchetti ◽  
Dick Pluim ◽  
Dilek Iusuf ◽  
Roberto Mazzanti ◽  
...  
Keyword(s):  
Drug Efflux ◽  
Efflux System ◽  
The Brain ◽  
Camptothecin Analogues

scholarly journals The MexJK Efflux Pump of Pseudomonas aeruginosa Requires OprM for Antibiotic Efflux but Not for Efflux of Triclosan

2002 ◽  
Vol 184 (18) ◽  
pp. 5036-5044 ◽  
Author(s):  
Rungtip Chuanchuen ◽  
Craig T. Narasaki ◽  
Herbert P. Schweizer
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Membrane Protein ◽  
Outer Membrane ◽  
Outer Membrane Protein ◽  
Efflux Pump ◽  
Resistant Mutant ◽  
Efflux System ◽  
Membrane Fusion Protein ◽  
Single Nucleotide Change ◽  
Antibiotic Efflux

ABSTRACT Using the biocide triclosan as a selective agent, several triclosan-resistant mutants of a susceptible Pseudomonas aeruginosa strain were isolated. Cloning and characterization of a DNA fragment conferring triclosan resistance from one of these mutants revealed a hitherto uncharacterized efflux system of the resistance nodulation cell division (RND) family, which was named MexJK and which is encoded by the mexJK operon. Expression of this operon is negatively regulated by the product of mexL, a gene located upstream of and transcribed divergently from mexJK. The triclosan-resistant mutant contained a single nucleotide change in mexL, which caused an amino acid change in the putative helix-turn-helix domain of MexL. The MexL protein belongs to the TetR family of repressor proteins. The MexJK system effluxed tetracycline and erythromycin but only in the presence of the outer membrane protein channel OprM; OprJ and OprN did not function with MexJK. Triclosan efflux required neither of the outer membrane protein channels tested but necessitated the MexJ membrane fusion protein and the MexK inner membrane RND transporter. The results presented in this study suggest that MexJK may function as a two-component RND pump for triclosan efflux but must associate with OprM to form a tripartite antibiotic efflux system. Furthermore, the results confirm that triclosan is an excellent tool for the study of RND multidrug efflux systems and that this popular biocide therefore readily selects mutants which are cross-resistant with antibiotics.

scholarly journals Effect of protein kinase inhibitors on the drug-efflux system in multidrug-resistant tumor cells

1990 ◽  
Vol 52 ◽  
pp. 86
Author(s):  
Shinya Wakusawa ◽  
Shigeo Nakamura ◽  
Kotomi Aritsuka ◽  
Ken-ichi Miyamoto ◽  
Ryozo Koshiura ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Tumor Cells ◽  
Kinase Inhibitors ◽  
Multidrug Resistant ◽  
Protein Kinase Inhibitors ◽  
Drug Efflux ◽  
Efflux System

scholarly journals Inhibition of Patched Drug Efflux Increases Vemurafenib Effectiveness against Resistant BrafV600E Melanoma

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1500 ◽  
Author(s):  
Laurie Signetti ◽  
Nelli Elizarov ◽  
Méliné Simsir ◽  
Agnès Paquet ◽  
Dominique Douguet ◽  
...  
Keyword(s):  
Proton Motive Force ◽  
Multidrug Transporter ◽  
Drug Efflux ◽  
Brafv600e Mutation ◽  
Multidrug Transporters ◽  
Xenograft Models ◽  
Melanoma Patients ◽  
Almost All ◽  
Sar Study ◽  
Human Xenograft Models

Melanoma patients harboring the BRAFV600E mutation are treated with vemurafenib. Almost all of them ultimately acquire resistance, leading to disease progression. Here, we find that a small molecule from a marine sponge, panicein A hydroquinone (PAH), overcomes resistance of BRAFV600E melanoma cells to vemurafenib, leading to tumor elimination in corresponding human xenograft models in mice. We report the synthesis of PAH and demonstrate that this compound inhibits the drug efflux activity of the Hedgehog receptor, Patched. Our SAR study allowed identifying a key pharmacophore responsible for this activity. We showed that Patched is strongly expressed in metastatic samples from a cohort of melanoma patients and is correlated with decreased overall survival. Patched is a multidrug transporter that uses the proton motive force to efflux drugs. This makes its function specific to cancer cells, thereby avoiding toxicity issues that are commonly observed with inhibitors of ABC multidrug transporters. Our data provide strong evidence that PAH is a highly promising lead for the treatment of vemurafenib resistant BRAFV600E melanoma.

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