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RND efflux pump

Stefanie Gerson, Jennifer Nowak, Esther Zander, Julia Ertel, Yurong Wen, Oleg Krut, Harald Seifert, Paul G Higgins
Objectives: To investigate the mechanisms of tigecycline resistance in isogenic Acinetobacter baumannii isolate pairs as well as 65 unique clinical A. baumannii isolates obtained during the MagicBullet clinical trial from Greece, Italy and Spain. Methods: A. baumannii isolates were subjected to WGS and the regulatory genes of resistance-nodulation-cell division (RND)-type efflux pumps were analysed. MICs were determined by agar dilution and the expression of RND-type efflux pumps was measured by semi-quantitative RT-PCR...
March 14, 2018: Journal of Antimicrobial Chemotherapy
Angharad E Green, Alejandro Amézquita, Yvan Le-Marc, Matthew J Bull, Thomas R Connor, Eshwar Mahenthiralingam
Pseudomonas aeruginosa (P. aeruginosa) is a common contaminant associated with product recalls in the home and personal care (HPC) industry. Preservation systems are used to prevent spoilage and protect consumers, but greater knowledge is needed of preservative resistance mechanisms used by P. aeruginosa contaminants. We aimed to identify genetic pathways associated with preservative exposure by using an industrial P. aeruginosa strain and implementing RNA-Seq to understand gene expression changes in response to industry relevant conditions...
March 14, 2018: FEMS Microbiology Letters
Yi-Hsiang Cheng, Tzu-Lung Lin, Yi-Tsung Lin, Jin-Town Wang
Background: Colistin is one of the last-resort antibiotics used to treat carbapenem-resistant Klebsiella pneumoniae infection. Our previous studies indicated that clinical strains encoding CrrB with amino acid substitutions exhibited higher colistin resistance (MICs ≥512 mg/L) than did colistin-resistant strains encoding mutant MgrB, PmrB or PhoQ. Objectives: CrrAB may regulate another unknown mechanism(s) contributing to colistin resistance, besides modifications of LPS with 4-amino-4-deoxy-l-arabinose and phosphoethanolamine...
February 28, 2018: Journal of Antimicrobial Chemotherapy
Fernando Andre Pereira Marques Duraes, Madalena Maria Magalhaes Pinto, Maria Emilia Silva Pereira de Sousa
Antibiotic resistance is one of the most pressing health issues of our days. It can arise due to a multiplicity of factors, such as target modification, decrease in the drug uptake, changes in the metabolic pathways and activation of efflux pumps. The overexpression of efflux pumps is responsible for the extrusion of drugs, making antibiotic therapy fail, as the quantity of intracellular antibiotic is not enough to provide the desired therapeutic effect. Efflux pumps can be included in five families according to their composition, nature of substrates, energy source, and number of transmembrane spanning regions...
February 9, 2018: Current Medicinal Chemistry
Attilio Vittorio Vargiu, Venkata Krishnan Ramaswamy, Giuliano Malloci, Ivana Malvacio, Alessio Atzori, Paolo Ruggerone
The putative mechanism by which bacterial RND-type multidrug efflux pumps recognize and transport their substrates is a complex and fascinating enigma of structural biology. How a single protein can recognize a huge number of unrelated compounds and transport them through one or just a few mechanisms is an amazing feature not yet completely unveiled. The appearance of cooperativity further complicates the understanding of structure-dynamics-activity relationships in these complex machineries. Experimental techniques may have limited access to the molecular determinants and to the energetics of key processes regulating the activity of these pumps...
January 30, 2018: Research in Microbiology
Derek S Sarovich, Jessica R Webb, Matthew C Pitman, Linda T Viberg, Mark Mayo, Robert W Baird, Jennifer M Robson, Bart J Currie, Erin P Price
Background: Burkholderia pseudomallei, the causative agent of the high-mortality disease melioidosis, is a Gram-negative bacterium that is naturally resistant to many antibiotics. There is no vaccine for melioidosis, and effective eradication is reliant on biphasic and prolonged antibiotic administration. The carbapenem drug, meropenem, is the current gold-standard option for treating severe melioidosis. Intrinsic B. pseudomallei resistance towards meropenem has not yet been documented; however, resistance could conceivably develop over the course of infection, leading to prolonged sepsis and treatment failure...
January 31, 2018: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
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
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
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 was investigated for comparative analysis...
December 29, 2017: Journal of Biomolecular Structure & Dynamics
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
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 5, 2017: Research in Microbiology
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 5, 2017: Research in Microbiology
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 multidrug-resistant opportunistic pathogen, harbors eight RND-type efflux pump operons. Of these, the smeU1VWU2X operon is unique for its possession of two additional genes, smeU1 and smeU2 , which encode proteins of the short-chain dehydrogenase/reductase (SDR) family...
February 2018: Antimicrobial Agents and Chemotherapy
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
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
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
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
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
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
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
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