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RND efflux pump

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https://www.readbyqxmd.com/read/29146106/the-hydrophobic-trap-the-achilles-heel-of-rnd-efflux-pumps
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
https://www.readbyqxmd.com/read/28867620/complete-genome-sequence-analysis-of-the-fish-pathogen-flavobacterium-columnare-provides-insights-into-antibiotic-resistance-and-pathogenicity-related-genes
#10
Yulei Zhang, Lijuan Zhao, Wenjie Chen, Yunmao Huang, Ling Yang, V Sarathbabu, Zaohe Wu, Jun Li, Pin Nie, Li Lin
We analyzed here the complete genome sequences of a highly virulent Flavobacterium columnare Pf1 strain isolated in our laboratory. The complete genome consists of a 3,171,081 bp circular DNA with 2784 predicted protein-coding genes. Among these, 286 genes were predicted as antibiotic resistance genes, including 32 RND-type efflux pump related genes which were associated with the export of aminoglycosides, indicating inducible aminoglycosides resistances in F. columnare. On the other hand, 328 genes were predicted as pathogenicity related genes which could be classified as virulence factors, gliding motility proteins, adhesins, and many putative secreted proteases...
October 2017: Microbial Pathogenesis
https://www.readbyqxmd.com/read/28806947/conessine-as-a-novel-inhibitor-of-multidrug-efflux-pump-systems-in-pseudomonas-aeruginosa
#11
Thanyaluck Siriyong, Potjanee Srimanote, Sasitorn Chusri, Boon-Ek Yingyongnarongkul, Channarong Suaisom, Varomyalin Tipmanee, Supayang Piyawan Voravuthikunchai
BACKGROUND: Holarrhena antidysenterica has been employed as an ethnobotanical plant for the treatment of dysentery, diarrhoea, fever, and bacterial infections. Biological activities of the principle compound, conessine including anti-diarrhoea and anti-plasmodial effects were documented. Our previous study reported potency of Holarrhena antidysenterica extract and conessine as resistance modifying agents against extensively drug-resistant Acinetobacter baumannii. This study aimed to investigate (i) whether conessine, a steroidal alkaloid compound, could act as a resistance modifying agent against multidrug-resistant Pseudomonas aeruginosa, and (ii) whether MexAB-OprM efflux pump involved in the mechanism...
August 14, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28720734/lack-of-acrb-efflux-function-confers-loss-of-virulence-on-salmonella-enterica-serovar-typhimurium
#12
Xuan Wang-Kan, Jessica M A Blair, Barbara Chirullo, Jonathan Betts, Roberto M La Ragione, Alasdair Ivens, Vito Ricci, Timothy J Opperman, Laura J V Piddock
AcrAB-TolC is the paradigm resistance-nodulation-division (RND) multidrug resistance efflux system in Gram-negative bacteria, with AcrB being the pump protein in this complex. We constructed a nonfunctional AcrB mutant by replacing D408, a highly conserved residue essential for proton translocation. Western blotting confirmed that the AcrB D408A mutant had the same native level of expression of AcrB as the parental strain. The mutant had no growth deficiencies in rich or minimal medium. However, compared with wild-type SL1344, the mutant had increased accumulation of Hoechst 33342 dye and decreased efflux of ethidium bromide and was multidrug hypersusceptible...
July 18, 2017: MBio
https://www.readbyqxmd.com/read/28631419/the-cpxr-cpxa-system-contributes-to-salmonella-gold-resistance-by-controlling-the-gols-dependent-gesabc-transcription
#13
Sebastián Cerminati, Germán F Giri, Julián I Mendoza, Fernando C Soncini, Susana K Checa
Several regulatory systems contribute to bacterial resistance to heavy metals controlling the expression of factors required to eliminate the intoxicant and/or to repair the damage caused by it. In Salmonella, the response to Au ions is mediated by the specific metalloregulator GolS that, among other genes, controls the expression of the RND-efflux pump GesABC. In this work, we demonstrate that CpxR/CpxA, a main cell-envelope stress-responding system, promotes gesABC transcription in the presence of Au ions at neutral pH...
June 19, 2017: Environmental Microbiology
https://www.readbyqxmd.com/read/28536672/response-to-bile-salts-in-clinical-strains-of-acinetobacter-baumannii-lacking-the-adeabc-efflux-pump-virulence-associated-with-quorum-sensing
#14
Maria López, Lucia Blasco, Eva Gato, Astrid Perez, Laura Fernández-Garcia, Luis Martínez-Martinez, Felipe Fernández-Cuenca, Jesús Rodríguez-Baño, Alvaro Pascual, German Bou, Maria Tomás
Introduction:Acinetobacter baumannii is an opportunistic nosocomial pathogen associated with multiple infections. This pathogen usually colonizes (first stage of microbial infection) host tissues that are in contact with the external environment. As one of the sites of entry in human hosts is the gastrointestinal tract, the pathogen must be capable of tolerating bile salts. However, studies analyzing the molecular characteristics involved in the response to bile salts in clinical strains of A. baumannii are scarce...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28462872/interaction-of-ethidium-and-tetraphenylphosphonium-cations-with-salmonella-enterica-cells
#15
Valeryia Mikalayeva, Sandra Sakalauskaitė, Rimantas Daugelavičius
BACKGROUND AND OBJECTIVE: One of the main causes of bacterial resistance to antimicrobials is multidrug resistance induced by the increased efficiency of the efflux pumps. In this study we analyzed how the conditions of assay affect the efflux of indicator substrates ethidium (Et(+)) and tetraphenylphosphonium (TPP(+)) in Salmonella enterica ser. Typhimurium cells. Impact of the outer membrane permeability barrier, composition and temperature of the medium on accumulation of the indicator compounds also was analyzed...
April 17, 2017: Medicina
https://www.readbyqxmd.com/read/28352264/indole-induced-activities-of-%C3%AE-lactamase-and-efflux-pump-confer-ampicillin-resistance-in-pseudomonas-putida-kt2440
#16
Jisun Kim, Bora Shin, Chulwoo Park, Woojun Park
Indole, which is widespread in microbial communities, has received attention because of its effects on bacterial physiology. Pseudomonas putida and Pseudomonas aeruginosa can acquire ampicillin (Amp) resistance during growth on indole-Amp agar. Transcriptome, mutant, and inhibitor studies have suggested that Amp resistance induced by indole can be attributed to increased gene expression of ttgAB encoding two genes of RND-type multidrug efflux operons and an ampC encoding β-lactamase. Expression, enzyme activities, and mutational analyses indicated that AmpC β-lactamase is important for acquiring Amp resistance of P...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28314727/transcriptomic-analyses-elucidate-adaptive-differences-of-closely-related-strains-of-pseudomonas-aeruginosa-in-fuel
#17
Thusitha S Gunasekera, Loryn L Bowen, Carol E Zhou, Susan C Howard-Byerly, William S Foley, Richard C Striebich, Larry C Dugan, Oscar N Ruiz
Pseudomonas aeruginosa can utilize hydrocarbons, but different strains have various degrees of adaptation despite their highly conserved genome. P. aeruginosa ATCC 33988 is highly adapted to hydrocarbons, while P. aeruginosa strain PAO1, a human pathogen, is less adapted and degrades jet fuel at a lower rate than does ATCC 33988. We investigated fuel-specific transcriptomic differences between these strains in order to ascertain the underlying mechanisms utilized by the adapted strain to proliferate in fuel...
May 15, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28275586/colistin-resistance-in-acinetobacter-baumannii-mdr-zj06-revealed-by-a-multiomics-approach
#18
Xiaoting Hua, Lilin Liu, Youhong Fang, Qiucheng Shi, Xi Li, Qiong Chen, Keren Shi, Yan Jiang, Hua Zhou, Yunsong Yu
Acinetobacter baumannii has emerged as an important opportunistic pathogen due to its ability to acquire resistance to most currently available antibiotics. Colistin is often considered as the last line of therapy for infections caused by multidrug-resistant A. baumannii (MDRAB). However, colistin-resistant A. baumannii strain has recently been reported. To explore how multiple drug-resistant A. baumannii responded to colistin resistance, we compared the genomic, transcriptional and proteomic profile of A. baumannii MDR-ZJ06 to the induced colistin-resistant strain ZJ06-200P5-1...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28230771/antibiotic-resistance-determinant-focused-acinetobacter-baumannii-vaccine-designed-using-reverse-vaccinology
#19
Zhaohui Ni, Yan Chen, Edison Ong, Yongqun He
As one of the most influential and troublesome human pathogens, Acinetobacter baumannii (A. baumannii) has emerged with many multidrug-resistant strains. After collecting 33 complete A. baumannii genomes and 84 representative antibiotic resistance determinants, we used the Vaxign reverse vaccinology approach to predict classical type vaccine candidates against A. baumannii infections and new type vaccine candidates against antibiotic resistance. Our genome analysis identified 35 outer membrane or extracellular adhesins that are conserved among all 33 genomes, have no human protein homology, and have less than 2 transmembrane helices...
February 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28210464/evaluation-of-efflux-pumps-gene-expression-in-resistant-pseudomonas-aeruginosa-isolates-in-an-iranian-referral-hospital
#20
Babak Pourakbari, Sahar Yaslianifard, Somaye Yaslianifard, Shima Mahmoudi, Sepideh Keshavarz-Valian, Setareh Mamishi
BACKGROUND AND OBJECTIVES: Pseudomonas aeruginosa (PA) is one of the most important causes of nosocomial infections and has an intrinsic resistance to many antibiotics. Among all the resistance-nodulation-division (RND) pumps of P. aeruginosa, MexAB-OprM is the first efflux pump found to target multiple classes of antibiotics. This study was aimed to evaluate the expression level of genes expressing MexAB-OprM in clinical isolates of P. aeruginosa. MATERIALS AND METHODS: In this study, 45 P...
August 2016: Iranian Journal of Microbiology
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