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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
Arlene J George, Yarely C Hoffiz, Antoinette J Charles, Ying Zhu, Angela M Mabb
Protein ubiquitination is a posttranslational modification that plays an integral part in mediating diverse cellular functions. The process of protein ubiquitination requires an enzymatic cascade that consists of a ubiquitin activating enzyme (E1), ubiquitin conjugating enzyme (E2) and an E3 ubiquitin ligase (E3). There are an estimated 600-700 E3 ligase genes representing ~5% of the human genome. Not surprisingly, mutations in E3 ligase genes have been observed in multiple neurological conditions. We constructed a comprehensive atlas of disrupted E3 ligase genes in common (CND) and rare neurological diseases (RND)...
2018: Frontiers in Genetics
Ahmad Al Jaghsi, Reiner Biffar, Christiane Pink, Torsten Mundt
PURPOSE: To demonstrate how data collected using the computerized planimetric method (CPM) can be analyzed by providing an example in which the amount of plaque accumulation and the efficacy of the rotating needles device (RND) in cleaning specific parts of partial removable dental prostheses (PRDPs) were estimated. MATERIALS AND METHODS: Thirty-four participants wearing a total of 41 double-crown-retained PRDPs with veneered secondary crowns were included in this study...
February 15, 2018: International Journal of Prosthodontics
Fang Chen, Ling Wang, Min Wang, Yixin Xie, Xiaomeng Xia, Xianping Li, Yanhua Liu, Wei Cao, Tingting Zhang, Pengling Li, Min Yang
The present study aimed to develop a rational therapy based on the genetic epidemiology, molecular mechanism evaluation and in vitro antibiotic combinations activity in multidrug-resistant Acinetobacter baumannii (MDRAB). MDRAB was screened by the Kirby-Bauer method. The random amplified polymorphic DNA technique was used to establish genetic fingerprinting, and a series of resistance genes were detected by polymerase chain reaction. Antimicrobial agents including amikacin (AK), cefoperazone/sulbactam (SCF I/II), meropenem (MEM), minocycline (MINO) and ciprofloxacin (CIP) were used to determine the minimum inhibitory concentrations (MICs) and interactions between antibiotics by the broth microdilution method and chequerboard assays...
February 2018: Oncology Letters
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
Arata Furukawa, Shintaro Nakayama, Kunihito Yoshikaie, Yoshiki Tanaka, Tomoya Tsukazaki
The membrane protein SecDF, belonging to the RND superfamily, enhances protein translocation at the extracytoplasmic side using a proton gradient. Here, we report the crystal structure of SecDF in a form we named Super-membrane-facing (Super F) form, demonstrating a β-barrel architecture instead of the previously reported β-sheet structure. Through this structural insight and supporting results of an in vivo crosslinking experiment, we propose a remote coupling model in which a structural change of the transmembrane region drives a functional, extracytoplasmic conformational transition...
January 26, 2018: Structure
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
X Renee Bina, Mondraya F Howard, Dawn L Taylor-Mulneix, Vanessa M Ante, Dillon E Kunkle, James E Bina
Resistance-nodulation-division (RND) efflux systems are ubiquitous transporters in Gram-negative bacteria that are essential for antibiotic resistance. The RND efflux systems also contribute to diverse phenotypes independent of antimicrobial resistance, but the mechanism by which they affect most of these phenotypes is unclear. This is the case in Vibrio cholerae where the RND systems function in antimicrobial resistance and virulence factor production. Herein, we investigated the linkage between RND efflux and V...
January 5, 2018: PLoS Pathogens
Jih-Sheng Yang, Jih-Jen Wu
The TiO2-based heterojunction nanodendrite (ND) array composed of anatase NPs (ANP) on the surface of rutile ND (RND) array is selected as the model photoanode to demonstrate the strategies towards eco-friendly and efficient solar water splitting using neutral electrolyte and seawater. Compared to the performances in alkaline electrolyte, non-negligible potential drop across the electrolyte as well as impeded charge injection and charge separation are monitored in the ANP/RND array photoanode with neutral electrolyte, which are respectively ascribed to the series resistance of neutral electrolyte, the fundamentally pH-dependent water oxidation mechanism on TiO2 surface, as well as the less band bending at the interface of TiO2 and neutral electrolyte...
January 4, 2018: ACS Applied Materials & Interfaces
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 were investigated for comparative analysis...
December 15, 2017: Journal of Biomolecular Structure & Dynamics
Xuejun C Zhang, Min Liu, Lei Han
Prokaryotic AcrB-like proteins belong to a family of transporters of the RND superfamily, and as main contributing factor to multidrug resistance pose a tremendous threat to future human health. A unique feature of AcrB transporters is the presence of two separate domains responsible for carrying substrate and generating energy. Significant progress has been made in elucidating the three-dimensional structures of the homo-trimer complexes of AcrB-like transporters, and a three-step functional rotation was identified for this class of transporters...
2017: Biophysics Reports
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
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