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RND efflux pump

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https://www.readbyqxmd.com/read/29335824/broad-spectrum-resistance-of-pseudomonas-aeruginosa-from-shellfish-infrequent-acquisition-of-novel-resistance-mechanisms
#1
Ana Maravić, Ivica Šamanić, Matilda Šprung, Željana Fredotović, Nada Ilić, Josipa Dragičević, Jasna Puizina
Pseudomonas aeruginosa is one the most common multidrug-resistant pathogens worldwide. It has been previously detected in marine shellfish, but its antibiotic resistance in such environment has not been explored. By combining PCR detection of acquired genes, and resistance-nodulation-cell division (RND) efflux studying, we investigated the multifactorial resistance traits of 108 P. aeruginosa isolates recovered from wild-growing Mediterranean mussels (Mytilus galloprovincialis) in Croatia. Eleven different resistance profiles were found, with the main mechanism being the overexpression of intrinsic efflux pump(s), particularly MexAB-OprM...
January 15, 2018: Environmental Monitoring and Assessment
https://www.readbyqxmd.com/read/29276505/contribution-of-raeb-a-putative-rnd-type-transporter-to-aminoglycoside-and-detergent-resistance-in-riemerella-anatipestifer
#2
Xin Zhang, Ming-Shu Wang, Ma-Feng Liu, De-Kang Zhu, Francis Biville, Ren-Yong Jia, Shun Chen, Kun-Feng Sun, Qiao Yang, Ying Wu, Xin-Xin Zhao, Xiao-Yue Chen, An-Chun Cheng
Riemerella anatipestifer is an important pathogenic bacterium that infects ducks. It exhibits resistance to multiple classes of antibiotics. Multidrug efflux pumps play a major role as a mechanism of antimicrobial resistance in Gram-negative pathogens and they are poorly understood in R. anatipestifer. In this study, a gene encoding the B739_0873 protein in R. anatipestifer CH-1, which belongs to the resistance-nodulation-cell division (RND) efflux pump family, was identified. With respect to the substrate specificity of B739_0873, the antibiotic susceptibility testing showed that the B739_0873 knockout strain was more sensitive to aminoglycosides and detergents than the wild-type strain...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29246087/in-silico-interaction-studies-suggest-rnd-efflux-pump-mediates-polymyxin-resistance-in-acinetobacter-baumannii
#3
Privita Verma, Pramila Maurya, Monalisa Tiwari, Vishvanath Tiwari
Bacterial efflux pumps have emerged as antibiotic resistance determinants and confers multi-drug resistance to a broad range of antimicrobials as well as non-antibiotic substances. A study about translocation of antibiotic molecules through the efflux transporter, will contribute in determining substrate specificity. In the present study, we have explored RND family efflux pump extensively found in Acinetobacter baumannii i.e. AdeABC. Besides, another well studied RND efflux pump, AcrAB-TolC together with a non-RND efflux pump, NorM were investigated for comparative analysis...
December 15, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/29235508/genetic-adaptation-of-microbial-populations-present-in-high-intensity-catfish-production-systems-with-therapeutic-oxytetracycline-treatment
#4
Qifan Zeng, Xiangli Tian, Luxin Wang
Microbial communities that are present in aquaculture production systems play significant roles in degrading organic matter, controlling diseases, and formation of antibiotic resistance. It is important to understand the diversity and abundance of microbial communities and their genetic adaptations associated with environmental physical and chemical changes. Here we collected water and sediment samples from a high-intensity catfish production system and its original water reservoir. The metagenomic analysis showed that Proteobacteria, Actinobacteria, Bacteroidetes, Cyanobacteria, and Firmicutes were the top five phyla identified from all samples...
December 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29217371/reconstitution-of-the-activity-of-rnd-efflux-pumps-a-bottoms-up-approach
#5
Dhenesh Puvanendran, Quentin Cece, Martin Picard
Efflux pumps are systems devoted to the extrusion of noxious compounds. In this review, we discuss the various strategies that have thus far been undertaken for the investigation of efflux pumps after reconstitution into liposomes. It is challenging to uncover mechanisms and dynamics of efflux pumps due to a number of characteristics: their function depends on the correct assembly of three components and they span two adjacent membranes whose lipid compositions are very different. In addition, efflux pumps are active transporters that need energy to work...
December 4, 2017: Research in Microbiology
https://www.readbyqxmd.com/read/29208490/fluorescence-enlightens-rnd-pump-activity-and-the-intrabacterial-concentration-of-antibiotics
#6
Muriel Masi, Estelle Dumont, Julia Vergalli, Jelena Pajovic, Matthieu Réfrégiers, Jean-Marie Pagès
To understand antibiotic resistance in Gram-negative bacteria, a key point is to investigate antibiotic accumulation, which is defined by influx and efflux. Several methods exist to evaluate membrane permeability and efflux pump activity, but they present disadvantages and limitations. An optimized spectrofluorimetric method using intrinsic tryptophan fluorescence as an internal standard, as well as a complementary microfluorimetric assay following time-course accumulation in intact individual cells, have been developed...
December 2, 2017: Research in Microbiology
https://www.readbyqxmd.com/read/29203487/role-of-smeu1vwu2x-operon-in-the-alleviation-of-oxidative-stresses-and-the-occurrence-of-sulfamethoxazole-trimethoprim-resistant-mutants-in-stenotrophomonas-maltophilia
#7
Chao-Jung Wu, Tsu-Ting Chiu, Yi-Tsung Lin, Yi-Wei Huang, Li-Hua Li, Tsuey-Ching Yang
Overexpression of resistance-nodulation-division (RND)-type efflux pumps is an important mechanism for bacteria to combat antimicrobials. RND efflux pumps are also critical for bacterial physiology such as oxidative stress tolerance. Stenotrophomonas maltophilia, a multi-drug resistant opportunistic pathogen, harbors eight RND-type efflux pump operons. Of them, smeU1VWU2X operon is unique for its possession of two additional genes, smeU1 and smeU2, which encode proteins of short-chain dehydrogenase/reductase (SDR) family...
December 4, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29177837/high-throughput-flow-cytometry-screening-of-multidrug-efflux-systems
#8
Mark K Haynes, Matthew Garcia, Ryan Peters, Anna Waller, Pietro Tedesco, Oleg Ursu, Cristian G Bologa, Radleigh G Santos, Clemencia Pinilla, Terry H Wu, Julie A Lovchik, Tudor I Oprea, Larry A Sklar, George P Tegos
The resistance nodulation cell division (RND) family of proteins are inner membrane transporters that associate with periplasmic adaptor proteins and outer membrane porins to affect substrate transport from the cytosol and periplasm in Gram-negative bacteria. Various structurally diverse compounds are substrates of RND transporters. Along with their notable role in antibiotic resistance, these transporters are essential for niche colonization, quorum sensing, and virulence as well as for the removal of fatty acids and bile salts...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29177832/molecular-modeling-of-multidrug-properties-of-resistance-nodulation-division-rnd-transporters
#9
Pierpaolo Cacciotto, Venkata K Ramaswamy, Giuliano Malloci, Paolo Ruggerone, Attilio V Vargiu
Efflux pumps of the resistance nodulation division (RND) superfamily are among the major contributors to intrinsic and acquired multidrug resistance in Gram-negative bacteria. Structural information on AcrAB-TolC and MexAB-OprM, major efflux pumps of Escherichia coli and Pseudomonas aeruginosa respectively, boosted intensive research aimed at understanding the molecular mechanisms ruling the active extrusion processes. In particular, several studies were devoted to the understanding of the determinants behind the extraordinary broad specificity of the RND transporters AcrB and MexB...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29177830/covalently-linked-trimers-of-rnd-resistance-nodulation-division-efflux-transporters-to-study-their-mechanism-of-action-escherichia-coli-acrb-multidrug-exporter-as-an-example
#10
Hiroshi Nikaido
Transporters undergo large conformational changes in their functional cycle. RND (Resistance-Nodulation-Division) family efflux transporters usually exist as homotrimers, and each protomer was proposed to undergo a cycle of conformational changes in succession so that at any given time the trimer would contain three protomers of different conformations, the functionally rotating mechanism of transport. This mechanism implies that the inactivation of one protomer among three will inactivate the entire trimeric ensemble by blocking the functional rotation...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29177829/biochemical-reconstitution-and-characterization-of-multicomponent-drug-efflux-transporters
#11
Martin Picard, Elena B Tikhonova, Isabelle Broutin, Shuo Lu, Alice Verchère, Helen I Zgurskaya
Efflux pumps are the major determinants in bacterial multidrug resistance. In Gram-negative bacteria, efflux transporters are organized as macromolecular tripartite machineries that span the two-membrane cell envelope of the bacterium. Biochemical data on purified proteins are essential to draw a mechanistic picture of this highly dynamical, multicomponent, efflux system. We describe protocols for the reconstitution and the in vitro study of transporters belonging to RND and ABC superfamilies: the AcrAB-TolC and MacAB-TolC efflux systems from Escherichia coli and the MexAB-OprM efflux pump from Pseudomonas aeruginosa...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29146106/the-hydrophobic-trap-the-achilles-heel-of-rnd-efflux-pumps
#12
Zachary Aron, Timothy J Opperman
Resistance-nodulation-division (RND) superfamily efflux pumps play a major role in multidrug resistance (MDR) of Gram-negative pathogens by extruding diverse classes of antibiotics from the cell. There has been considerable interest in developing efflux pump inhibitors (EPIs) of RND pumps as adjunctive therapies. The primary challenge in EPI discovery has been the highly hydrophobic, poly-specific substrate binding site of the target. Recent findings have identified the hydrophobic trap, a narrow phenylalanine-lined groove in the substrate-binding site, as the "Achilles heel" of the RND efflux pumps...
November 13, 2017: Research in Microbiology
https://www.readbyqxmd.com/read/29128373/regulation-of-the-acrab-tolc-efflux-pump-in-enterobacteriaceae
#13
Natasha Weston, Prateek Sharma, Vito Ricci, Laura J V Piddock
Bacterial multidrug efflux systems are a major mechanism of antimicrobial resistance and are fundamental to the physiology of Gram-negative bacteria. The resistance-nodulation-division (RND) family of efflux pumps is the most clinically significant, as it is associated with multidrug resistance. Expression of efflux systems is subject to multiple levels of regulation, involving local and global transcriptional regulation as well as post-transcriptional and post-translational regulation. The best-characterised RND system is AcrAB-TolC, which is present in Enterobacteriaceae...
November 8, 2017: Research in Microbiology
https://www.readbyqxmd.com/read/29118749/hoisting-loop-in-bacterial-multidrug-exporter-acrb-is-a-highly-flexible-hinge-that-enables-the-large-motion-of-the-subdomains
#14
Martijn Zwama, Katsuhiko Hayashi, Keisuke Sakurai, Ryosuke Nakashima, Kimie Kitagawa, Kunihiko Nishino, Akihito Yamaguchi
The overexpression of RND-type exporters is one of the main causes of multidrug resistance (MDR) in Gram-negative pathogens. In RND transporters, such as Escherichia coli's main efflux pump AcrB, drug efflux occurs in the porter domain, while protons flow through the transmembrane domain: remote conformational coupling. At the border of a transmembrane helix (TM8) and subdomain PC2, there is a loop which makes a hoisting movement by a random-coil-to-α-helix change, and opens and closes a drug channel entrance...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29050760/mmps5-mmpl5-as-an-efflux-pump-in-mycobacterium-species
#15
REVIEW
Julien Briffotaux, Wei Huang, Xinwei Wang, Brigitte Gicquel
Tuberculosis remains an important cause of morbidity and mortality throughout the world, amplified by the expansion of antibiotic resistance. Increasing active efflux of the antibiotic is one of the several strategies used by bacteria to resist to antibiotics. After showing the importance of the RND superfamily of efflux pumps in drug resistance, this review focuses on the protein MmpL5, a transmembrane transporter of Mycobacterium. These exporters should be involved in the variety of roles in bacterial cells, including expelling various drugs...
December 2017: Tuberculosis
https://www.readbyqxmd.com/read/29042652/computational-analysis-of-the-molecular-mechanism-of-ramr-mutations-contributing-to-antimicrobial-resistance-in-salmonella-enterica
#16
Yen-Yi Liu, Chih-Chieh Chen
Antimicrobial resistance (AMR) in pathogenic microorganisms with multidrug resistance (MDR) constitutes a severe threat to human health. A major causative mechanism of AMR is mediated through the multidrug efflux pump (MEP). The resistance-nodulation-division superfamily (RND family) of Gram-negative bacteria is usually the major cause of MDR in clinical studies. In Salmonella enterica, the RND pump is translated from the arcAB gene, which is regulated by the activator RamA. Many MEP-caused AMR strains have high ramA gene expression due to mutations in RamR, which has a homodimeric structure comprising the dimerization domain and DNA-binding domain (DBD)...
October 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28922614/mexxy-efflux-pump-overexpression-and-aminoglycoside-resistance-in-cystic-fibrosis-isolates-of-pseudomonas-aeruginosa-from-chronic-infections
#17
Manu Singh, Yvonne C W Yau, Shirley Wang, Valerie Waters, Ayush Kumar
In this study, we analyzed 15 multidrug-resistant cystic fibrosis isolates of Pseudomonas aeruginosa from chronic lung infections for expression of 4 different multidrug efflux systems (MexAB-OprM, MexCD-OprJ, MexEF-OprN, and MexXY), using quantitative reverse transcriptase PCR. Overexpression of MexXY pump was observed in all of the isolates tested. Analysis of regulatory genes that control the expression of these 4 efflux pumps revealed a number of previously uncharacterized mutations. Our work shows that MexXY pump overexpression is common in cystic fibrosis isolates and could be contributing to their reduced aminoglycoside susceptibility...
September 18, 2017: Canadian Journal of Microbiology
https://www.readbyqxmd.com/read/28916560/cmeabc-multidrug-efflux-pump-contributes-to-antibiotic-resistance-and-promotes-campylobacter-jejuni-survival-and-multiplication-in-acanthamoeba-polyphaga
#18
Ana Vieira, Amritha Ramesh, Alan M Seddon, Andrey V Karlyshev
Campylobacter jejuni is a foodborne pathogen recognized as the leading cause of human bacterial gastroenteritis. The wide use of antibiotics in medicine and in animal husbandry has led to an increased incidence of antibiotic resistance in Campylobacter In addition to a role in multidrug resistance, the Campylobacter CmeABC RND-type efflux pump, which is associated with multidrug resistance (MDR), may also be involved in virulence. As a vehicle of pathogenic microorganisms, the protozoan Acanthamoeba is a good model for the investigation of bacterial survival in the environment and molecular mechanisms of pathogenicity...
September 15, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28900249/effect-of-efflux-pump-inhibition-on-pseudomonas-aeruginosa-transcriptome-and-virulence
#19
Giordano Rampioni, Cejoice Ramachandran Pillai, Francesca Longo, Roslen Bondì, Valerio Baldelli, Marco Messina, Francesco Imperi, Paolo Visca, Livia Leoni
Efflux pumps of the resistance-nodulation-cell-division (RND) family increase antibiotic resistance in many bacterial pathogens, representing candidate targets for the development of antibiotic adjuvants. RND pumps have also been proposed to contribute to bacterial infection, implying that efflux pump inhibitors (EPIs) could also act as anti-virulence drugs. Nevertheless, EPIs are usually investigated only for their properties as antibiotic adjuvants, while their potential anti-virulence activity is seldom taken into account...
September 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28890187/kinetic-analysis-of-the-inhibition-of-the-drug-efflux-protein-acrb-using-surface-plasmon-resonance
#20
Rumana Mowla, Yinhu Wang, Shutao Ma, Henrietta Venter
Multidrug efflux protein complexes such as AcrAB-TolC from Escherichia coli are paramount in multidrug resistance in Gram-negative bacteria and are also implicated in other processes such as virulence and biofilm formation. Hence efflux pump inhibition, as a means to reverse antimicrobial resistance in clinically relevant pathogens, has gained increased momentum over the past two decades. Significant advances in the structural and functional analysis of AcrB have informed the selection of efflux pump inhibitors (EPIs)...
September 7, 2017: Biochimica et Biophysica Acta
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