RamA Is an Alternate Activator of the Multidrug Resistance Cascade in Enterobacter aerogenes

ABSTRACT Multidrug resistance (MDR) in Enterobacter aerogenes can be mediated by induction of MarA, which is triggered by certain antibiotics and phenolic compounds. In this study, we identified the gene encoding RamA, a 113-amino-acid regulatory protein belonging to the AraC-XylS transcriptional activator family, in the Enterobacter aerogenes ATCC 13048 type strain and in a clinical multiresistant isolate. Overexpression of RamA induced an MDR phenotype in drug-susceptible Escherichia coli JM109 and E. aerogenes ATCC 13048, as demonstrated by 2- to 16-fold-increased resistance to β-lactams, tetracycline, chloramphenicol, and quinolones, a decrease in porin production, and increased production of AcrA, a component of the AcrAB-TolC drug efflux pump. We show that RamA enhances the transcription of the marRAB operon but is also able to induce an MDR phenotype in a mar-deleted strain. We demonstrate here that RamA is a transcriptional activator of the Mar regulon and is also a self-governing activator of the MDR cascade.

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SMAR1 repression by pluripotency factors and consequent chemoresistance in breast cancer stem-like cells is reversed by aspirin

Science Signaling ◽

10.1126/scisignal.aay6077 ◽

2020 ◽

Vol 13 (654) ◽

pp. eaay6077

Author(s):

Apoorva Bhattacharya ◽

Shravanti Mukherjee ◽

Poulami Khan ◽

Shruti Banerjee ◽

Apratim Dutta ◽

...

Keyword(s):

Efflux Pump ◽

Chemotherapy Resistance ◽

Cooperative Interaction ◽

Drug Efflux ◽

Cancer Stemness ◽

Gene Encoding ◽

Pluripotency Factors ◽

Tumor Bearing ◽

Drug Efflux Pumps ◽

Drug Efflux Pump

The high abundance of drug efflux pumps in cancer stem cells (CSCs) contributes to chemotherapy resistance. The transcriptional regulator SMAR1 suppresses CSC expansion in colorectal cancer, and increased abundance of SMAR1 is associated with better prognosis. Here, we found in breast tumors that the expression of SMAR1 was decreased in CSCs through the cooperative interaction of the pluripotency factors Oct4 and Sox2 with the histone deacetylase HDAC1. Overexpressing SMAR1 sensitized CSCs to chemotherapy through SMAR1-dependent recruitment of HDAC2 to the promoter of the gene encoding the drug efflux pump ABCG2. Treating cultured CSCs or 4T1 tumor-bearing mice with the nonsteroidal anti-inflammatory drug aspirin restored SMAR1 expression and ABCG2 repression and enhanced tumor sensitivity to doxorubicin. Our findings reveal transcriptional mechanisms regulating SMAR1 that also regulate cancer stemness and chemoresistance and suggest that, by restoring SMAR1 expression, aspirin might enhance chemotherapeutic efficacy in patients with stem-like tumors.

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Identification and Evolution of Drug Efflux Pump in Clinical Enterobacter aerogenes Strains Isolated in 1995 and 2003

PLoS ONE ◽

10.1371/journal.pone.0003203 ◽

2008 ◽

Vol 3 (9) ◽

pp. e3203 ◽

Cited By ~ 36

Author(s):

Jacqueline Chevalier ◽

Céline Mulfinger ◽

Eric Garnotel ◽

Pierre Nicolas ◽

Anne Davin-Régli ◽

...

Keyword(s):

Efflux Pump ◽

Enterobacter Aerogenes ◽

Drug Efflux ◽

Drug Efflux Pump

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The human multidrug resistance-associated protein MRP is a plasma membrane drug-efflux pump.

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.91.19.8822 ◽

1994 ◽

Vol 91 (19) ◽

pp. 8822-8826 ◽

Cited By ~ 403

Author(s):

G. J. Zaman ◽

M. J. Flens ◽

M. R. van Leusden ◽

M. de Haas ◽

H. S. Mulder ◽

...

Keyword(s):

Plasma Membrane ◽

Multidrug Resistance ◽

Efflux Pump ◽

Drug Efflux ◽

Drug Efflux Pump

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Resistance to Cationic Surfactants and Some Other Agents of Escherichia coli Recombinants with an Abundant Number of Genes Encoding Drug Efflux Pump.

Biocontrol Science ◽

10.4265/bio.7.115 ◽

2002 ◽

Vol 7 (2) ◽

pp. 115-120

Author(s):

SHU ISHIKAWA ◽

YOSHINOBU MATSUMURA ◽

TETSUAKI TSUCHIDO

Keyword(s):

Escherichia Coli ◽

Cationic Surfactants ◽

Efflux Pump ◽

Drug Efflux ◽

Number Of Genes ◽

Genes Encoding ◽

Drug Efflux Pump

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Human hepatocellular carcinoma cell lines exhibit multidrug resistance unrelated to MRD1 gene expression

Journal of Cell Science ◽

10.1242/jcs.98.3.317 ◽

1991 ◽

Vol 98 (3) ◽

pp. 317-322

Author(s):

D.W. Shen ◽

Y.G. Lu ◽

K.V. Chin ◽

I. Pastan ◽

M.M. Gottesman

Keyword(s):

Hepatocellular Carcinoma ◽

Multidrug Resistance ◽

Cancer Cells ◽

Cell Lines ◽

Actinomycin D ◽

Efflux Pump ◽

Mdr1 Gene ◽

Drug Efflux ◽

P Glycoprotein ◽

Drug Efflux Pump

Multidrug resistance of human cancer cells may result from expression of P-glycoprotein, the product of the MRD1 gene, acting as an energy-dependent drug efflux pump. However, direct evidence that expression of the MDR1 gene contributes to the multidrug resistance of human liver carcinomas has not been established. In this study, we tested five cell lines derived from human hepatocellular carcinomas for sensitivity to a variety of drugs used widely as anticancer agents; these included vinblastine, doxorubicin, actinomycin D, mitomycin C, 5-fluorouracil, 6-mercaptopurine, melphalan, methotrexate, cis-platinum and etoposide (VP-16). All five hepatoma cell lines were resistant at different levels to these chemicals compared to human KB cells. Although it has been demonstrated that resistance to vinblastine, colchicine, doxorubicin and actinomycin D in human multidrug-resistant cells is associated with overexpression of P-glycoprotein, very little expression of P-glycoprotein was found in these human hepatoma cells. Neither verapamil nor quinidine, inhibitors of the drug efflux pump, were able to overcome multidrug resistance in hepatoma cells. These results indicate that the multidrug resistance phenotype in human hepatocellular carcinoma cells cannot be attributed to expression of the MDR1 gene, but that novel mechanisms may account for the resistance of these cancer cells.

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Berberine reverses multidrug resistance in Candida albicans by hijacking the drug efflux pump Mdr1p

Science Bulletin ◽

10.1016/j.scib.2020.12.035 ◽

2020 ◽

Author(s):

Yaojun Tong ◽

Jingyu Zhang ◽

Nuo Sun ◽

Xiang-Ming Wang ◽

Qi Wei ◽

...

Keyword(s):

Candida Albicans ◽

Multidrug Resistance ◽

Efflux Pump ◽

Drug Efflux ◽

Drug Efflux Pump

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Membrane homoeostasis and multidrug resistance in yeast

Bioscience Reports ◽

10.1042/bsr20080071 ◽

2008 ◽

Vol 28 (4) ◽

pp. 217-228 ◽

Cited By ~ 17

Author(s):

Sneh Lata Panwar ◽

Ritu Pasrija ◽

Rajendra Prasad

Keyword(s):

Multidrug Resistance ◽

Efflux Pump ◽

Efflux Pumps ◽

Membrane Lipid ◽

Major Facilitator Superfamily ◽

Drug Efflux ◽

Proper Functioning ◽

Drug Efflux Pumps ◽

Drug Efflux Pump ◽

Major Facilitator

The development of MDR (multidrug resistance) in yeast is due to a number of mechanisms. The most documented mechanism is enhanced extrusion of drugs mediated by efflux pump proteins belonging to either the ABC (ATP-binding cassette) superfamily or MFS (major facilitator superfamily). These drug-efflux pump proteins are localized on the plasma membrane, and the milieu therein affects their proper functioning. Several recent studies demonstrate that fluctuations in membrane lipid composition affect the localization and proper functioning of the MDR efflux pump proteins. Interestingly, the efflux pumps of the ABC superfamily are particularly susceptible to imbalances in membrane-raft lipid constituents. This review focuses on the importance of the membrane environment in functioning of the drug-efflux pumps and explores a correlation between MDR and membrane lipid homoeostasis.

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Role of AbeS, a Novel Efflux Pump of the SMR Family of Transporters, in Resistance to Antimicrobial Agents in Acinetobacter baumannii

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00748-09 ◽

2009 ◽

Vol 53 (12) ◽

pp. 5312-5316 ◽

Cited By ~ 64

Author(s):

Vijaya Bharathi Srinivasan ◽

Govindan Rajamohan ◽

Wondwossen A. Gebreyes

Keyword(s):

Escherichia Coli ◽

Acinetobacter Baumannii ◽

Antimicrobial Agents ◽

Efflux Pump ◽

Multidrug Resistant ◽

Drug Efflux ◽

Drug Efflux Pump ◽

Resistance Expression ◽

Multidrug Resistant Strain

ABSTRACT In this study, a chromosomally encoded putative drug efflux pump of the SMR family, named AbeS, from a multidrug-resistant strain of Acinetobacter baumannii was characterized to elucidate its role in antimicrobial resistance. Expression of the cloned abeS gene in hypersensitive Escherichia coli host KAM32 resulted in decreased susceptibility to various classes of antimicrobial agents, detergents, and dyes. Deletion of the abeS gene in A. baumannii confirmed its role in conferring resistance to these compounds.

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Lectin detection of cell surface saccharides remodeling induced by development of P-glycoprotein mediated multidrug resistance phenotype in L1210 leukemia cells

Acta Chimica Slovaca ◽

10.2478/acs-2014-0010 ◽

2014 ◽

Vol 7 (1) ◽

pp. 52-56 ◽

Cited By ~ 2

Author(s):

Mário Šereš ◽

Lucia Pavlíková ◽

Zdena Sulová ◽

Albert Breier

Keyword(s):

Multidrug Resistance ◽

Cell Surface ◽

Efflux Pump ◽

L1210 Cell ◽

Leukemia Cells ◽

Drug Efflux ◽

L1210 Leukemia ◽

P Glycoprotein ◽

Drug Efflux Pump ◽

State Of Art

Abstract P-glycoprotein is an ATP dependent drug efflux pump the expression of which is responsible for strong depression of cell sensitivities to large group of structurally unrelated substances in neoplastic cells. We found that the expression of this protein in mice leukemia cells L1210 is associated with massive remodeling of cell surface saccharides. This remodeling is consistent with the alteration of cellular contents of UDP-sugars, glycogen and glycoproteins when P-gp positive and P-gp negative L1210 cell variants were compared. The current paper is focused on bringing the state of art information about this topic.

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