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https://www.readbyqxmd.com/read/28807921/candida-albicans-swi-snf-and-mediator-complexes-differentially-regulate-mrr1-induced-mdr1-expression-and-fluconazole-resistance
#1
Zhongle Liu, Lawrence C Myers
Long-term azole treatment of patients with chronic Candida albicans infections can lead to drug resistance. Gain-of-function (GOF) mutations in the transcription factor Mrr1 and the consequent transcriptional activation of MDR1, a drug efflux coding gene, is a common pathway by which this human fungal pathogen acquires fluconazole resistance. This work elucidates the previously unknown downstream transcription mechanisms utilized by hyperactive Mrr1. We've identified the Swi/Snf chromatin remodeling complex as a key co-activator for Mrr1, which is required to maintain basal and induced 'open' chromatin, and Mrr1 occupancy, at the MDR1 promoter...
August 14, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28807920/mediator-tail-module-is-required-for-tac1-activated-cdr1-expression-and-azole-resistance-in-candida-albicans
#2
Zhongle Liu, Lawrence C Myers
The human fungal pathogen Candida albicans develops drug resistance after long-term exposure to azole drugs in the treatment of chronic candidiasis. Gain-of-function (GOF) mutations in the transcription factor Tac1, and the consequent expression of its targets, drug efflux pumps Cdr1 and Cdr2, are a common mechanism by which C. albicans acquires fluconazole resistance. The mechanism by which GOF mutations hyperactivate Tac1 is currently unknown. Here, we define a transcriptional activation domain (TAD) at the C-terminus of Tac1...
August 14, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28806947/conessine-as-a-novel-inhibitor-of-multidrug-efflux-pump-systems-in-pseudomonas-aeruginosa
#3
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/28805978/obeticholic-acid-a-selective-farnesoid-x-receptor-agonist-regulates-bile-acid-homeostasis-in-sandwich-cultured-human-hepatocytes
#4
Yuanyuan Zhang, Jonathan P Jackson, Robert L St Claire, Kimberly Freeman, Kenneth R Brouwer, Jeffrey E Edwards
Farnesoid X receptor (FXR) is a master regulator of bile acid homeostasis through transcriptional regulation of genes involved in bile acid synthesis and cellular membrane transport. Impairment of bile acid efflux due to cholangiopathies results in chronic cholestasis leading to abnormal elevation of intrahepatic and systemic bile acid levels. Obeticholic acid (OCA) is a potent and selective FXR agonist that is 100-fold more potent than the endogenous ligand chenodeoxycholic acid (CDCA). The effects of OCA on genes involved in bile acid homeostasis were investigated using sandwich-cultured human hepatocytes...
August 2017: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/28805111/chemoresistance-in-cancer-cells-exosomes-as-potential-regulators-of-therapeutic-tumor-heterogeneity
#5
Aman Sharma
Drug resistance in cancer cells remains a fundamental challenge. Be it nontargeted or targeted drugs, the presence of intrinsic or acquired cancer cell resistance remains a great obstacle in chemotherapy. Conventionally, a spectrum of cellular mechanisms defines drug resistance including overexpression of antiapoptotic proteins and drug efflux pumps, mutations in target and synergistic activation of prosurvival pathways in tumor cells. In addition to these well-studied routes, exosome-induced chemoresistance is emerging as a novel mechanism...
August 14, 2017: Nanomedicine
https://www.readbyqxmd.com/read/28799332/attaching-the-nora-efflux-pump-inhibitor-inf55-to-methylene-blue-enhances-antimicrobial-photodynamic-inactivation-of-methicillin-resistant-staphylococcus-aureus-in-vitro-and-in-vivo
#6
Ardeshir Rineh, Naveen K Dolla, Anthony R Ball, Maria Magana, John B Bremner, Michael R Hamblin, George P Tegos, Michael J Kelso
Antimicrobial photodynamic inactivation (aPDI) uses photosensitizers (PSs) and harmless visible light to generate reactive oxygen species (ROS) and kill microbes. Multidrug efflux systems can moderate the phototoxic effects of PSs by expelling the compounds from cells. We hypothesized that increasing intracellular concentrations of PSs by inhibiting efflux with a covalently attached efflux pump inhibitor (EPI) would enhance bacterial cell phototoxicity and reduce exposure of neighbouring host cells to damaging ROS...
August 11, 2017: ACS Infectious Diseases
https://www.readbyqxmd.com/read/28797043/next-generation-sequencing-reveals-the-antibiotic-resistant-variants-in-the-genome-of-pseudomonas-aeruginosa
#7
Babu Ramanathan, Hassan Mahmood Jindal, Cheng Foh Le, Ranganath Gudimella, Arif Anwar, Rozaimi Razali, Johan Poole-Johnson, Rishya Manikam, Shamala Devi Sekaran
Rapid progress in next generation sequencing and allied computational tools have aided in identification of single nucleotide variants in genomes of several organisms. In the present study, we have investigated single nucleotide polymorphism (SNP) in ten multi-antibiotic resistant Pseudomonas aeruginosa clinical isolates. All the draft genomes were submitted to Rapid Annotations using Subsystems Technology (RAST) web server and the predicted protein sequences were used for comparison. Non-synonymous single nucleotide polymorphism (nsSNP) found in the clinical isolates compared to the reference genome (PAO1), and the comparison of nsSNPs between antibiotic resistant and susceptible clinical isolates revealed insights into the genome variation...
2017: PloS One
https://www.readbyqxmd.com/read/28790997/tetracycline-resistance-genes-identified-from-distinct-soil-environments-in-china-by-functional-metagenomics
#8
Shaochen Wang, Xia Gao, Yuejiao Gao, Yanqing Li, Mingming Cao, Zhenhua Xi, Lixing Zhao, Zhiyang Feng
Soil microbiota represents one of the ancient evolutionary origins of antibiotic resistance and has been increasingly recognized as a potentially vast unstudied reservoir of resistance genes with possibilities to exchange with pathogens. Tetracycline resistance is one of the most abundant antibiotic resistances that may transfer among clinical and commensal microorganisms. To investigate tetracycline resistance genes from soil bacteria in different habitats, we performed functional analysis of three metagenomic libraries derived from soil samples collected from Yunnan, Sichuan, and Tibet, respectively, in China...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28782709/mic-distribution-among-wild-type-strains-of-legionella-pneumophila-identifies-a-subpopulation-with-reduced-susceptibility-to-macrolides-owing-to-efflux-pump-genes
#9
Marine Vandewalle-Capo, Clémence Massip, Ghislaine Descours, Joséphine Charavit, Joelle Chastang, Pierre Alain Billy, Sandrine Boisset, Gerard Lina, Christophe Gilbert, Max Maurin, Sophie Jarraud, Christophe Ginevra
Legionnaires' disease is a severe pneumonia mainly caused by Legionella pneumophila, and which is treated by antibiotics. The purpose of this study was to describe the susceptibility of clinical strains of Legionella pneumophila to seven antibiotics used for legionellosis treatment. The minimum inhibitory concentrations (MICs) of 109 well-characterized clinical strains of L. pneumophila serogroup-1 were determined using a broth microdilution method without charcoal and compared to antibiotic-resistant strains selected in vitro...
August 4, 2017: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/28781959/structure-based-design-of-ferritin-nanoparticle-immunogens-displaying-antigenic-loops-of-neisseria-gonorrhoeae
#10
Liqin Wang, Daniel Xing, Adriana Le Van, Ann E Jerse, Shuishu Wang
Effective vaccines are urgently needed to combat gonorrhea, a common sexually transmitted bacterial infection, for which treatment options are diminishing due to rapid emergence of antibiotic resistance. We have used a rational approach to the development of gonorrhea vaccines, and genetically engineered nanoparticles to present antigenic peptides of Neisseria gonorrhoeae, the causative agent of gonorrhea. We hypothesized that the ferritin nanocage could be used as a platform to display an ordered array of N...
August 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/28781367/bacterial-physiology-efflux-pumps-fitness-and-virulence
#11
Andrea Du Toit
No abstract text is available yet for this article.
September 2017: Nature Reviews. Microbiology
https://www.readbyqxmd.com/read/28781060/antibacterial-activity-of-exogenous-glutathione-and-its-synergism-on-antibiotics-sensitize-carbapenem-associated-multidrug-resistant-clinical-isolates-of-acinetobacter-baumannii
#12
Roaa Alharbe, Ayidh Almansour, Dong H Kwon
A major clinical impact of A. baumannii is hospital-acquired infections including ventilator-associated pneumonia. The treatment of this pathogen is often difficult due to its innate and acquired resistance to almost all commercially available antibiotics. Infections with carbapenem-associated multidrug resistant A. baumannii is the most problematic. Glutathione is a tripeptide thiol-antioxidant and antibacterial activity of exogenous glutathione was reported in some bacteria. However, clinical relevance and molecular details of the antibacterial activity of glutathione are currently unclear...
July 29, 2017: International Journal of Medical Microbiology: IJMM
https://www.readbyqxmd.com/read/28779982/redox-sensitive-cationic-pullulan-for-efficient-gene-transfection-and-drug-retention-in-c6-glioma-cells
#13
Priya S S, Rekha M R
Thiolated cationic pullulan was synthesized by conjugating pullulan with polyethyleneimine (PEI) and mercaptosuccinic acid (MSA). The formed conjugate was oxidized to obtain disulfide linked cationic pullulan (PPMSS). PPMSS exhibited good buffering capacity and nanoplexes formulated were of size less than 150nm. Nanoplexes formed with PPMSS are redox sensitive and susceptible to reductive cleavage by dithiothreitol (DTT) ensuring the intracellular release of DNA. In vitro, cytotoxic evaluation studies of polymers in C6 cell lines established its non-toxic nature...
August 2, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28771141/risk-factors-and-molecular-mechanisms-associated-with-trimethoprim-sulfamethoxazole-resistance-in-stenotrophomonas-maltophilia-in-mexico
#14
Sandra Abril Herrera-Heredia, César Pezina-Cantú, Elvira Garza-González, Paola Bocanegra-Ibarias, Soraya Mendoza-Olazarán, Rayo Morfín-Otero, Adrián Camacho-Ortiz, Licet Villarreal-Treviño, Eduardo Rodríguez-Noriega, Laura Paláu-Davila, Héctor Jesús Maldonado-Garza, Samantha Flores-Treviño
PURPOSE: Stenotrophomonas maltophilia is a multidrug-resistant opportunistic pathogen causing an increasing number of nosocomial infections. Our aim was to evaluate the risk factors and mechanisms associated with trimethoprim-sulfamethoxazole (SXT) resistance in S. maltophilia infections in Mexico. METHODOLOGY: Clinical isolates and patients' demographic and clinical data were collected from February 2007 to August 2015 in two tertiary-care hospitals in Mexico. Antimicrobial susceptibility and analysis of sul and SmeABC and SmeDEF efflux pump overexpression were performed in all isolates...
August 4, 2017: Journal of Medical Microbiology
https://www.readbyqxmd.com/read/28770910/coarse-grained-simulations-of-conformational-changes-in-the-multidrug-efflux-transporter-acrb
#15
Yead Jewel, Jin Liu, Prashanta Dutta
The multidrug resistance (MDR) system actively pumps antibiotics out of cells causing serious health problems. During the pumping, AcrB (one of the key components of MDR) undergoes a series of large-scale and proton-motive conformational changes. Capturing the conformational changes through all-atom simulations is challenging. Here, we implement a hybrid coarse-grained force field to investigate the conformational changes of AcrB in the porter domain under different protonation states of Asp407/Asp408 in the trans-membrane domain...
August 3, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28770446/biofilm-formation-and-antibiotic-susceptibility-in-dispersed-cells-versus-planktonic-cells-from-clinical-industry-and-environmental-origins
#16
Mercedes Berlanga, Laura Gomez-Perez, Ricardo Guerrero
We examined the cell-surface physicochemical properties, the biofilm formation capability and the antibiotic susceptibility in dispersed cells (from an artificial biofilm of alginate beads) and compared with their planktonic (free-swimming) counterparts. The strains used were from different origins, such as clinical (Acinetobacter baumannii AB4), cosmetic industry (Klebsiella oxytoca EU213, Pseudomonas aeruginosa EU190), and environmental (Halomonas venusta MAT28). In general, dispersed cells adhered better to surfaces (measured as the "biofilm index") and had a greater hydrophobicity [measured as the microbial affinity to solvents (MATS)] than planktonic cells...
August 2, 2017: Antonie Van Leeuwenhoek
https://www.readbyqxmd.com/read/28761097/structures-and-transport-dynamics-of-a-campylobacter-jejuni-multidrug-efflux-pump
#17
Chih-Chia Su, Linxiang Yin, Nitin Kumar, Lei Dai, Abhijith Radhakrishnan, Jani Reddy Bolla, Hsiang-Ting Lei, Tsung-Han Chou, Jared A Delmar, Kanagalaghatta R Rajashankar, Qijing Zhang, Yeon-Kyun Shin, Edward W Yu
Resistance-nodulation-cell division efflux pumps are integral membrane proteins that catalyze the export of substrates across cell membranes. Within the hydrophobe-amphiphile efflux subfamily, these resistance-nodulation-cell division proteins largely form trimeric efflux pumps. The drug efflux process has been proposed to entail a synchronized motion between subunits of the trimer to advance the transport cycle, leading to the extrusion of drug molecules. Here we use X-ray crystallography and single-molecule fluorescence resonance energy transfer imaging to elucidate the structures and functional dynamics of the Campylobacter jejuni CmeB multidrug efflux pump...
August 1, 2017: Nature Communications
https://www.readbyqxmd.com/read/28758624/tolc2-is-required-for-the-resistance-colonization-and-virulence-of-actinobacillus-pleuropneumoniae
#18
Ying Li, Sanjie Cao, Luhua Zhang, Jianlin Yuan, Yusheng Yang, Zhuang Zhu, Yiping Wen, Rui Wu, Qin Zhao, Xiaobo Huang, Qigui Yan, Yong Huang, Xiaoping Ma, Xintian Wen
PURPOSE: To colonize and cause infection in the host, pathogens must be well equipped to respond to and survive in several hostile conditions. TolC, an outer membrane channel component used by multidrug efflux pumps and type I secretion systems, is considered to be largely involved in bacterial physiology and virulence. In this study, we attempted to investigate the possible roles of TolC2, a homologue of TolC, in the pathogenesis of Actinobacillus pleuropneumoniae. METHODOLOGY: The cell viability was investigated under stress conditions (oxidative, thermal, acid and osmotic)...
July 31, 2017: Journal of Medical Microbiology
https://www.readbyqxmd.com/read/28757036/the-phenotypic-and-molecular-resistance-induced-by-a-single-exposure-to-sub-mutant-prevention-concentration-of-marbofloxacin-in-salmonella-typhimurium-isolates-from-swine
#19
Seung-Jin Lee, Na-Hye Park, Abraham Fikru Mechesso, Kwang-Jick Lee, Seung-Chun Park
In the present study, the molecular mechanisms of antibiotic resistance in Salmonella Typhimurium clinical isolates from pigs were investigated using a single-step mutation model of exposure to sub-mutant prevention concentrations (MPCs) of marbofloxacin. The minimum inhibitory concentrations (MICs) of seven antibacterial drugs were evaluated against 30 S. Typhimurium clinical isolates from different pigs. MPCs of marbofloxacin were also determined. The mechanism of marbofloxacin-resistance was investigated by sequencing analysis of target gene mutations and quantifying the overexpression of efflux pumps and their regulators by quantitative RT-PCR...
August 2017: Veterinary Microbiology
https://www.readbyqxmd.com/read/28755374/reconstitution-of-membrane-proteins-in-liposomes
#20
Alice Verchère, Isabelle Broutin, Martin Picard
Membrane protein reconstitution in liposomes is an invaluable technique to study numerous properties of membrane proteins in vitro. Kinetics, substrate specificity, and protein-protein interaction of membrane proteins can be investigated once they are embedded in the liposome bilayer. Both protocols described here aim to investigate the efflux pump MexA-MexB-OprM from Pseudomonas aeruginosa, a proteins complex embedded in both membranes of this Gram-negative bacteria. This tri-partite system, which by-passes the periplams, is involved in antibiotic resistance...
2017: Methods in Molecular Biology
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