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Efflux pumps

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https://www.readbyqxmd.com/read/28935182/eudesmane-sesquiterpenes-from-chinese-liverwort-are-substrates-of-cdrs-and-display-antifungal-activity-by-targeting-erg6-and-erg11-of-candida-albicans
#1
Siwen Li, Hongzhuo Shi, Wenqiang Chang, Yi Li, Ming Zhang, Yanan Qiao, Hongxiang Lou
We isolated twelve sesquiterpenes from Chinese liverwort Tritomaria quinquedentata (Huds.) Buch., including four new compounds. Among them, five eudesmane sesquiterpenes were ineffective against Candida albicans wild strain SC5314 but active towards efflux pumps-deficient strain DSY654 using Alamar blue assay. Further test of the most active agent of ent-isoalantolactone (8, ent-iLL) showed that it also inhibited the yeast-to-hyphal switch of DSY654 cells. The intracellular content measurement using high performance liquid chromatography (HPLC) revealed that ent-iLL was intracellularly accumulated in C...
September 9, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28934482/mechanistic-insight-into-how-multidrug-resistant-acinetobacter-baumannii-response-regulator-ader-recognizes-an-intercistronic-region
#2
Yurong Wen, Zhenlin Ouyang, Yue Yu, Xiaorong Zhou, Yingmei Pei, Bart Devreese, Paul G Higgins, Fang Zheng
AdeR-AdeS is a two-component regulatory system, which controls expression of the adeABC efflux pump involved in Acinetobacter baumannii multidrug resistance. AdeR is a response regulator consisting of an N-terminal receiver domain and a C-terminal DNA-binding-domain. AdeR binds to a direct-repeat DNA in the intercistronic region between adeR and adeABC. We demonstrate a markedly high affinity binding between unphosphorylated AdeR and DNA with a dissociation constant of 20 nM. In addition, we provide a 2.75 Å crystal structure of AdeR DNA-binding-domain complexed with the intercistronic DNA...
September 19, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28934375/into-the-wild-parallel-transcriptomics-of-the-tsetse-wigglesworthia-mutualism-within-kenyan-populations
#3
Miguel Medina Munoz, Adam R Pollio, Hunter L White, Rita V M Rio
Tsetse flies (Diptera: Glossinidae) have medical significance as the obligate vectors of African trypanosomes. In addition, tsetse harbor a simple gut microbiota. A predominant gut microbiota member, the Gammaproteobacterium Wigglesworthia spp., has coevolved with tsetse for a significant portion of Glossina radiation proving critical to tsetse fitness. Although multiple roles have been described for Wigglesworthia within colony flies, little research has been dedicated towards functional characterization within wild tsetse...
September 1, 2017: Genome Biology and Evolution
https://www.readbyqxmd.com/read/28932278/assessment-of-antibiotic-susceptibility-in-lactobacillus-isolates-from-chickens
#4
Marta Dec, Renata Urban-Chmiel, Dagmara Stępień-Pyśniak, Andrzej Wernicki
BACKGROUND: The aim of this study was to determine the susceptibility of 88 Lactobacillus isolates derived from chickens to antibiotic substances and to detect drug-resistance genes. RESULTS: The minimal inhibitory concentration of 13 antimicrobial substances was determined by the broth microdilution method, and resistance genes were detected by PCR. We recorded a high prevalence of resistance to tiamulin (90% resistant isolates), tetracyclines (74%) and lincomycin (70%), and a moderately high frequency of resistance to enrofloxacin (48%), macrolides (42%), aminoglycosides (12...
2017: Gut Pathogens
https://www.readbyqxmd.com/read/28927840/chemical-composition-and-modulation-of-bacterial-drug-resistance-of-the-essential-oil-from-leaves-of-croton-grewioides
#5
Vivianne Marcelino de Medeiros, Yuri Mangueira do Nascimento, Augusto Lopes Souto, Sara Alves Lucena Madeiro, Vicente Carlos de Oliveira Costa, Suellen Maria P M Silva, Vivyanne Dos Santos Falcão Silva, Maria de Fátima Agra, José Pinto de Siqueira-Júnior, Josean Fechine Tavares
The essential oil from leaves of Croton grewioides Baill was obtained by hydrodistillation using Clevenger apparatus, and its chemical composition was analyzed by GC-MS, where 18 compounds were identified, mostly as monoterpenes (55.56%) and sesquiterpenes (44.44%), in which the major constituent was the α-pinene (47.43%). The essential oil of Croton grewioides (EOCg) and its major compound (α-pinene) were evaluated as modulators of antibiotic resistance in strain SA-1199B and IS-58 of Staphylococcus aureus that overexpresses efflux protein...
September 16, 2017: Microbial Pathogenesis
https://www.readbyqxmd.com/read/28927230/multi-azole-resistant-strains-of-cryptococcus-neoformans-var-grubii-isolated-from-a-flz-resistant-strain-by-culturing-in-medium-containing-voriconazole
#6
Rui Kano, Miki Okubo, Atsuhiko Hasegawa, Hiroshi Kamata
A Cryptococcus neoformans var. grubii strain, NUBS14020, was the first fluconazole (FLZ)-resistant strain isolated from a feline cryptococcosis. Subsequent work demonstrated that multi-azole-resistant strains are readily isolated from FLZ-resistant strains by culturing in medium containing voriconazole (VRZ). The resulting clones were assessed for mutation and expression of known target genes, including the loci encoding lanosterol 14-α demethylase (ERG11), an ATP-binding cassette (ABC) transporter (AFR1), or a multidrug efflux pump (MEP); mutation and/or overexpression of these genes is known to be associated with azole resistance...
September 11, 2017: Medical Mycology: Official Publication of the International Society for Human and Animal Mycology
https://www.readbyqxmd.com/read/28926285/the-role-of-acrab-tolc-efflux-pump-in-mediating-fluoroquinolone-resistance-in-naturally-occurring-salmonella-isolates-from-china
#7
Jinling Shen, Baowei Yang, Qiang Gu, Guodong Zhang, Jielin Yang, Feng Xue, Jingdong Shao, Xiaojuan Yi, Yuan Jiang
The involvement of AcrAB-TolC efflux pump in regulating fluoroquinolone resistance of naturally occurring Salmonella isolates is insufficiently investigated. In this study, the regulatory genes, acrR, ramR, marRAB, and soxRS of AcrAB-TolC efflux pump, of 27 naturally occurring fluoroquinolone-resistant Salmonella isolates collected in China were sequenced. The expression levels of acrB, ramA, marA, and soxS were also examined using quantitative real-time polymerase chain reaction. Gene alterations were mainly observed for acrR (three mutation types) and ramR (four mutation types), not for marRAB (no mutation) or soxRS (one mutaton type)...
September 19, 2017: Foodborne Pathogens and Disease
https://www.readbyqxmd.com/read/28922614/mexxy-efflux-pump-overexpression-and-aminoglycoside-resistance-in-cystic-fibrosis-isolates-of-i-pseudomonas-aeruginosa-i-from-chronic-infections
#8
Manu Singh, Yvonne 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 four 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 four 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/28919409/solasodine-3-o-%C3%AE-d-glucopyranoside-is-hydrolyzed-by-a-membrane-glucosidase-into-active-molecule-solasodine-against-candida-albicans
#9
Wenqiang Chang, Ying Li, Sha Zheng, Ming Zhang, Yanhui Gao, Hongxiang Lou
Antifungal activity of some natural molecules can be abated or blocked by efflux pumps in Candida albicans, which restricts the discovery of potential antifungal agents. Here we found that the steroidal alkaloid solasodine is active against C. albicans efflux pump-deficient strains but inert towards the wild type. However, the glucosylated solasodine-3-O-β-d-glucopyranoside exhibits antifungal activity towards the wild type strain. Further investigation revealed that the entry of solasodine into C. albicans cells is blocked by efflux pumps...
September 15, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28917834/hexameric-assembly-of-membrane-fusion-protein-yknx-of-the-sporulation-delaying-efflux-pump-from-bacillus-amyloliquefaciens
#10
Yongbin Xu, Inseong Jo, Lulu Wang, Jinli Chen, Shengdi Fan, Yuesheng Dong, Chun-Shan Quan, Nam-Chul Ha
Membrane fusion proteins (MFPs) play an essential role in the action of the drug efflux pumps and protein secretion systems in bacteria. The sporulation delaying protein (SDP) efflux pump YknWXYZ has been identified in diverse Bacillus species. The MFP YknX requires the ATP-binding cassette (ABC) transporter YknYZ and the Yip1 family protein YknW to form a functional complex. To date, the crystal structure, molecular function and mechanism of action of YknX remain unknown. In this study, to characterize the structural and biochemical roles of YknX in the functional assembly of YknWXYZ from B...
September 13, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28916560/cmeabc-multidrug-efflux-pump-contributes-to-antibiotic-resistance-and-promotes-campylobacter-jejuni-survival-and-multiplication-in-acanthamoeba-polyphaga
#11
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/28916321/analysis-of-resistance-genes-in-pan-resistant-myroides-odoratimimus-clinical-strain-pr63039-using-whole-genome-sequencing
#12
Desong Ming, Qing-Qing Chen, Xiao-Tin Chen
To clarify the antibiotic resistance mechanisms of Myroides odoratimimus, pan-resistant M. odoratimimus strain PR63039 was isolated and its genome sequenced and analyzed. Antimicrobial susceptibility testing was conducted using the Kirby-Bauer disk diffusion method, and the Phoenix-100 Automated Microbiology System with a NMIC/ID-4 panel including aminoglycosides, β-lactams, polypeptides, quinolones, sulfonamides, chloramphenicols, and tetracyclines. Single-molecule real-time whole genome sequencing was conducted using the PacBio RSII system, and genome annotation was performed using RAST and IMG ER...
September 12, 2017: Microbial Pathogenesis
https://www.readbyqxmd.com/read/28915956/dual-inhibition-of-p-glycoprotein-and-midkine-may-increase-therapeutic-effects-of-anticancer-drugs
#13
A Şükrü Aynacıoğlu, Ayhan Bilir, Kenji Kadomatsu
Multidrug resistance (MDR) to chemotherapy may significantly affect the outcome of cancer treatment. ATP-dependent drug efflux pumps, including P-glycoprotein (P-gp), contribute to the resistance of various chemotherapeutic agents. Overexpression of P-gp in tumor cells induces chemoresistance via pumping the anticancer drugs out of the cells. In addition to taking part in many biological processes such as development, reproduction and repair, midkine (MK) also plays important roles in the pathogenesis of malignant diseases as well as in the regulation of MDR...
September 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/28912036/dual-effects-of-the-pi3k-inhibitor-zstk474-on-multidrug-efflux-pumps-in-resistant-cancer-cells
#14
Divya Muthiah, Richard Callaghan
ZSTK474 is a potent phosphoinositide 3-kinase (PI3K) inhibitor that reduces cell proliferation via G1-arrest. However, there is little information on the susceptibility of this anticancer drug to resistance conferred by the multidrug pumps P-glycoprotein (ABCB1) and ABCG2. We have demonstrated that ZSTK474 generated cytotoxicity in cells over-expressing either pump with potency similar to that in drug sensitive cells. In addition, the co-administration of ZSTK474 with the cytotoxic anti-cancer drugs vinblastine and mitoxantrone caused a potentiated cytotoxic effect in both drug sensitive and efflux pump expressing cells...
September 11, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28904944/antibacterial-and-antibiotic-modifying-activity-of-methanol-extracts-from-six-cameroonian-food-plants-against-multidrug-resistant-enteric-bacteria
#15
Joachim K Dzotam, Victor Kuete
The present work was designed to investigate the antibacterial activities of methanol extracts from six Cameroonian edible plants and their synergistic effects with some commonly used antibiotics against multidrug-resistant (MDR) Gram-negative bacteria expressing active efflux pumps. The extracts were subjected to qualitative phytochemical screening and the microdilution broth method was used for antibacterial assays. The results of phytochemical tests indicate that all tested crude extracts contained polyphenols, flavonoids, triterpenes, and steroids...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28904414/identification-of-arsenic-resistance-genes-from-marine-sediment-metagenome
#16
Nar Singh Chauhan, Sonam Nain, Rakesh Sharma
A metagenomic library of sea sediment metagenome containing 245,000 recombinant clones representing ~ 2.45 Gb of sea sediment microbial DNA was constructed. Two unique arsenic resistance clones, A7 and A12, were identified by selection on sodium arsenite containing medium. Clone A7 showed a six-fold higher resistance to arsenate [As(V)], a three-fold higher resistance to arsenite [As(III)] and significantly increased resistance to antimony [Sb(III)], while clone A12 showed increased resistance only to sodium arsenite and not to the other two metalloids...
September 2017: Indian Journal of Microbiology
https://www.readbyqxmd.com/read/28903357/intratumoral-acidosis-fosters-cancer-induced-bone-pain-through-the-activation-of-the-mesenchymal-tumor-associated-stroma-in-bone-metastasis-from-breast-carcinoma
#17
Gemma Di Pompo, Silvia Lemma, Lorenzo Canti, Nadia Rucci, Marco Ponzetti, Costantino Errani, Davide Maria Donati, Shonagh Russell, Robert Gillies, Tokuhiro Chano, Nicola Baldini, Sofia Avnet
Cancer-induced bone pain (CIBP) is common in patients with bone metastases (BM), significantly impairing quality of life. The current treatments for CIBP are limited since they are often ineffective. Local acidosis derived from glycolytic carcinoma and tumor-induced osteolysis is only barely explored cause of pain. We found that breast carcinoma cells that prefer bone as a metastatic site have very high extracellular proton efflux and expression of pumps/ion transporters associated with acid-base balance (MCT4, CA9, and V-ATPase)...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28900249/effect-of-efflux-pump-inhibition-on-pseudomonas-aeruginosa-transcriptome-and-virulence
#18
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/28899514/citral-a-monoterpenoid-aldehyde-interacts-synergistically-with-norfloxacin-against-methicillin-resistant-staphylococcus-aureus
#19
Priyanka Gupta, Dinesh Kumar Patel, Vivek Kumar Gupta, Anirban Pal, Sudeep Tandon, M P Darokar
BACKGROUND: Staphylococcus aureus (SA), is a major human pathogen causing wide range of clinical infections, which has been further complicated by drug resistance like methicillin resistant S. aureus (MRSA), vancomycin intermediate S. aureus (VISA)/vancomycin resistant S. aureus (VRSA), etc. The present study was aimed at determining anti-staphylococcal potential of citral against drug resistant clinical isolates alone and in combination with antibiotics. PURPOSE: To assess the potential of citral in combination with norfloxacin in treating drug resistant infections of SA...
October 15, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/28898293/the-vibrio-cholerae-var-regulon-encodes-a-metallo-%C3%AE-lactamase-and-an-antibiotic-efflux-pump-which-are-regulated-by-varr-a-lysr-type-transcription-factor
#20
Hong-Ting Victor Lin, Teresa Massam-Wu, Chen-Ping Lin, Yen-Jen Anna Wang, Yu-Chi Shen, Wen-Jung Lu, Pang-Hung Hsu, Yu-Hou Chen, Maria Ines Borges-Walmsley, Adrian Robert Walmsley
The genome sequence of V. cholerae O1 Biovar Eltor strain N16961 has revealed a putative antibiotic resistance (var) regulon that is predicted to encode a transcriptional activator (VarR), which is divergently transcribed relative to the putative resistance genes for both a metallo-β-lactamase (VarG) and an antibiotic efflux-pump (VarABCDEF). We sought to test whether these genes could confer antibiotic resistance and are organised as a regulon under the control of VarR. VarG was overexpressed and purified and shown to have β-lactamase activity against penicillins, cephalosporins and carbapenems, having the highest activity against meropenem...
2017: PloS One
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