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https://www.readbyqxmd.com/read/28339594/in-vivo-development-of-fluconazole-resistance-in-serial-cryptococcus-gattii-isolates-from-a-cat
#1
Jane E Sykes, Greg Hodge, Anil Singapuri, Mai Lee Yang, Angie Gelli, George R Thompson
Elevated fluconazole minimum inhibitory concentrations (MICs) are more frequently observed in Cryptococcus gattii compared to C. neoformans isolates; however, the development of in vivo resistance and the molecular mechanisms responsible have not been reported for this species. We report a case of Cryptococcus gattii (molecular type VGIII) that developed reduced susceptibility to fluconazole during therapy and delineate the molecular mechanisms responsible. Multilocus sequence typing and quantitative DNA analysis of the pre- and post-treatment isolates was performed using well-characterized methods...
October 7, 2016: Medical Mycology: Official Publication of the International Society for Human and Animal Mycology
https://www.readbyqxmd.com/read/28332827/subcellular-chemical-imaging-of-antibiotics-in-single-bacteria-using-c60-secondary-ion-mass-spectrometry
#2
Hua Tian, David A Six, Thomas Krucker, Jennifer A Leeds, Nicholas Winograd
The inherent difficulty of discovering new and effective antibacterials and the rapid development of resistance particularly in Gram-negative bacteria, illustrates the urgent need for new methods that enable rational drug design. Here we report the development of 3D imaging cluster secondary ion mass spectrometry (SIMS) as a label-free approach to chemically map small molecules in aggregated and single Escherichia coli cells, with ~300 nm spatial resolution and high chemical sensitivity. The feasibility of quantitative analysis was explored, and a non-linear relationship between treatment dose and signal for tetracycline and ampicillin, two clinically-used antibacterials, was observed...
March 23, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28331838/bibliometric-analysis-of-literature-on-antifungal-triazole-resistance-1980-2015
#3
Waleed M Sweileh, Ansam F Sawalha, Samah Al-Jabi, Sa'ed H Zyoud
BACKGROUND: Triazole antifungal agents play an important role in the treatment of a wide range of fungal infections. Little is known about antifungal triazole drug resistance when compared to antibiotic resistance. Therefore, this study was carried out to give a bibliometric overview of literature on triazole antifungal drug resistance. METHODS: Keywords related to triazole drug class and resistance were used in a search query in the Scopus search engine. The time span was set from 1980 to 2015...
March 2017: Germs
https://www.readbyqxmd.com/read/28329127/listeria-monocytogenes-cadc-regulates-cadmium-efflux-and-fine-tunes-lipoprotein-localization-to-escape-the-host-immune-response-and-promote-infection
#4
Rita Pombinho, Ana Camejo, Ana Vieira, Olga Reis, Filipe Carvalho, Maria Teresa Almeida, Jorge Campos Pinheiro, Sandra Sousa, Didier Cabanes
Listeria monocytogenes (Lm) is a major intracellular human foodborne bacterial pathogen. We previously revealed Lm-cadC as highly expressed during mouse infection. Here we show that Lm-CadC is a sequence-specific, DNA-binding and cadmium-dependent regulator of CadA, an efflux pump conferring cadmium resistance. CadC, but not CadA, is required for Lm infection in vivo. Interestingly, CadC also directly represses lspB, a gene encoding a lipoprotein signal peptidase whose expression appears detrimental for infection...
March 9, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28319068/iron-addiction-a-novel-therapeutic-target-in-ovarian-cancer
#5
D Basuli, L Tesfay, Z Deng, B Paul, Y Yamamoto, G Ning, W Xian, F McKeon, M Lynch, C P Crum, P Hegde, M Brewer, X Wang, L D Miller, N Dyment, F M Torti, S V Torti
Ovarian cancer is a lethal malignancy that has not seen a major therapeutic advance in over 30 years. We demonstrate that ovarian cancer exhibits a targetable alteration in iron metabolism. Ferroportin (FPN), the iron efflux pump, is decreased, and transferrin receptor (TFR1), the iron importer, is increased in tumor tissue from patients with high grade but not low grade serous ovarian cancer. A similar profile of decreased FPN and increased TFR1 is observed in a genetic model of ovarian cancer tumor-initiating cells (TICs)...
March 20, 2017: Oncogene
https://www.readbyqxmd.com/read/28314727/transcriptomic-analyses-elucidate-adaptive-differences-of-closely-related-strains-of-p-aeruginosa-in-fuel
#6
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 varying degrees of adaptation despite their highly conserved genome. P. aeruginosa ATCC 33988 is highly adapted to hydrocarbons while strain PAO1, a human pathogen, is less-adapted and degrades jet fuel at a slower rate than does ATCC 33988. We investigated fuel specific transcriptomic differences between these strains in order to ascertain the underling mechanisms utilized by the adapted strain to proliferate in fuel. During growth in fuel, the genes related to alkane degradation, heat-shock response, membrane proteins, efflux pumps and several novel genes were upregulated in ATCC 33988...
March 17, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28314281/chemosensitizing-properties-of-%C3%AE-caryophyllene-and-%C3%AE-caryophyllene-oxide-in-combination-with-doxorubicin-in-human-cancer-cells
#7
Silvia DI Giacomo, Antonella DI Sotto, Gabriela Mazzanti, Michael Wink
BACKGROUND/AIM: The natural sesquiterpenes β-caryophyllene (CRY) and β-caryophyllene oxide (CRYO) were evaluated for their potential chemosensitizing properties. MATERIALS AND METHODS: CRY and CRYO cytotoxicity was tested against the Caco-2, CCRF/CEM and CEM/ADR5000 human cancer cell lines. Furthermore, combination experiments were carried out in order to study the ability of the sesquiterpenes to increase doxorubicin cytotoxicity. The possible interference of CRY and CRYO with functionality of ATP-binding cassette (ABC)-transporters was also investigated by Rhodamine123 efflux assay...
March 2017: Anticancer Research
https://www.readbyqxmd.com/read/28303820/characterisation-of-antimicrobial-resistance-in-salmonellae-during-2014-2015-from-four-centres-across-india-an-icmr-antimicrobial-resistance-surveillance-network-report
#8
Sushila Dahiya, Priyanka Sharma, Bhavana Kumari, Sangeeta Pandey, Rooma Malik, Neelam Manral, Balaji Veeraraghavan, Agila Kumari Pragasam, Pallab Ray, Vikas Gautam, Sujata Sistla, Subhash Chandra Parija, Kamini Walia, Vinod Ohri, Bimal Kumar Das, Seema Sood, Arti Kapil
PURPOSE: The main purpose of this study was to establish 'Antimicrobial Resistance Surveillance Network' in India and to monitor the antimicrobial susceptibility profile of clinical isolates to establish a national network across the country for monitoring antimicrobial resistance in Salmonella. MATERIALS AND METHODS: This study was conducted at All India Institute of Medical Sciences, nodal centre with clinical isolates of Salmonellae collected from four centres across India, which included Christian Medical College, Vellore; Postgraduate Institute of Medical Education and Research, Chandigarh and Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry...
January 2017: Indian Journal of Medical Microbiology
https://www.readbyqxmd.com/read/28302529/gene-expression-modulation-of-abc-transporter-genes-in-response-to-permethrin-in-adults-of-the-mosquito-malaria-vector-anopheles-stephensi
#9
Valentina Mastrantonio, Marco Ferrari, Sara Epis, Agata Negri, Giulia Scuccimarra, Matteo Montagna, Guido Favia, Daniele Porretta, Sandra Urbanelli, Claudio Bandi
Living organisms have evolved an array of genes coding for detoxifying enzymes and efflux protein pumps, to cope with endogenous and xenobiotic toxic compounds. The study of the genes activated during toxic exposure is relevant to the area of arthropod vector control, since these genes are one of the targets upon which natural selection acts for the evolution of insecticide resistance. ATP-binding cassette (ABC) transporters participate to insecticide detoxification acting as efflux pumps, that reduce the intracellular concentration of toxic compounds, or of their metabolic derivatives...
March 13, 2017: Acta Tropica
https://www.readbyqxmd.com/read/28302074/clonality-outer-membrane-proteins-profile-and-efflux-pump-in-kpc-producing-enterobacter-sp-in-brazil
#10
Juliana Ferraz Rosa, Camila Rizek, Ana Paula Marchi, Thais Guimaraes, Lourdes Miranda, Claudia Carrilho, Anna S Levin, Silvia F Costa
BACKGROUND: Carbapenems resistance in Enterobacter spp. has increased in the last decade, few studies, however, described the mechanisms of resistance in this bacterium. This study evaluated clonality and mechanisms of carbapenems resistance in clinical isolates of Enterobacter spp. identified in three hospitals in Brazil (Hospital A, B and C) over 7-year. METHODS: Antibiotics sensitivity, pulsed-field gel electrophoresis (PFGE), PCR for carbapenemase and efflux pump genes were performed for all carbapenems-resistant isolates...
March 17, 2017: BMC Microbiology
https://www.readbyqxmd.com/read/28301084/the-effect-of-verapamil-a-p-glycoprotein-inhibitor-on-the-pharmacokinetics-of-peficitinib-an-orally-administered-once-daily-jak-inhibitor
#11
Tong Zhu, Corrie Howieson, Tomasz Wojtkowski, Jay P Garg, David Han, Ogert Fisniku, James Keirns
Peficitinib is an orally administered, once-daily Janus kinase inhibitor currently in development for the treatment of rheumatoid arthritis. It has been shown to be a P-glycoprotein (P-gp) substrate in vitro. The effects of verapamil, an inhibitor of the efflux pump P-gp, on the pharmacokinetic profile of peficitinib were assessed in this open-label, single-center, single-sequence, crossover drug-interaction study. Twenty-four healthy volunteers received a single 150-mg dose of peficitinib on days 1 and 12 of a 14-day treatment period and received verapamil 80 mg 3 times daily on days 5-14...
March 16, 2017: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/28295690/azole-resistance-in-candida-albicans-from-animals-highlights-on-efflux-pump-activity-and-gene-overexpression
#12
Marcos Fábio Gadelha Rocha, Silviane Praciano Bandeira, Lucas Pereira de Alencar, Luciana Magalhães Melo, Jamille Alencar Sales, Manoel de Araújo Neto Paiva, Carlos Eduardo Cordeiro Teixeira, Débora de Souza Collares Maia Castelo-Branco, Waldemiro de Aquino Pereira-Neto, Rossana de Aguiar Cordeiro, José Júlio Costa Sidrim, Raimunda Sâmia Nogueira Brilhante
This study investigated potential mechanisms of azole resistance among Candida albicans from animals, including efflux pump activity, ergosterol content and gene expression. For this purpose, 30 azole-resistant C. albicans strains from animals were tested for their antifungal susceptibility, according to document M27-A3, efflux pump activity by rhodamine 6G test, ergosterol content and expression of the genes CDR1, CDR2, MDR1, ERG11 by RT-qPCR. These strains were resistant to at least one azole derivative...
March 10, 2017: Mycoses
https://www.readbyqxmd.com/read/28294992/new-roads-leading-to-old-destinations-efflux-pumps-as-targets-to-reverse-multidrug-resistance-in-bacteria
#13
REVIEW
Gabriella Spengler, Annamária Kincses, Márió Gajdács, Leonard Amaral
Multidrug resistance (MDR) has appeared in response to selective pressures resulting from the incorrect use of antibiotics and other antimicrobials. This inappropriate application and mismanagement of antibiotics have led to serious problems in the therapy of infectious diseases. Bacteria can develop resistance by various mechanisms and one of the most important factors resulting in MDR is efflux pump-mediated resistance. Because of the importance of the efflux-related multidrug resistance the development of new therapeutic approaches aiming to inhibit bacterial efflux pumps is a promising way to combat bacteria having over-expressed MDR efflux systems...
March 15, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28293855/growth-hormone-receptor-knockdown-sensitizes-human-melanoma-cells-to-chemotherapy-by-attenuating-expression-of-abc-drug-efflux-pumps
#14
Reetobrata Basu, Nicholas Baumgaertel, Shiyong Wu, John J Kopchick
Melanoma remains one of the most therapy-resistant forms of human cancer despite recent introductions of highly efficacious targeted therapies. The intrinsic therapy resistance of human melanoma is largely due to abundant expression of a repertoire of xenobiotic efflux pumps of the ATP-binding cassette (ABC) transporter family. Here, we report that GH action is a key mediator of chemotherapeutic resistance in human melanoma cells. We investigated multiple ABC efflux pumps (ABCB1, ABCB5, ABCB8, ABCC1, ABCC2, ABCG1, and ABCG2) reportedly associated with melanoma drug resistance in different human melanoma cells and tested the efficacy of five different anti-cancer compounds (cisplatin, doxorubicin, oridonin, paclitaxel, vemurafenib) with decreased GH action...
March 14, 2017: Hormones & Cancer
https://www.readbyqxmd.com/read/28291698/detection-and-analysis-of-different-interactions-between-resistance-mechanisms-and-carbapenems-in-clinical-isolates-of-klebsiella-pneumoniae
#15
Tanise Vendruscolo Dalmolin, Bianca Vendruscolo Bianchini, Grazielle Guidolin Rossi, Ana Carolina Ramos, Ana Cristina Gales, Priscila de Arruda Trindade, Marli Matiko Anraku de Campos
Carbapenems are considered last-line agents for the treatment of serious infections caused by Klebsiella pneumoniae, and this microorganism may exhibit resistance to β-lactam antibiotics due to different mechanisms of resistance. We evaluated 27 isolates of K. pneumoniae resistant to carbapenems recovered from inpatients at the University Hospital of Santa Maria-RS from July 2013 to August 2014. We carried out antimicrobial susceptibility, carbapenemase detection, testing for the presence of efflux pump by broth microdilution and loss of porin by sodium dodecyl sulfate polyacrylamide gel electrophoresis...
February 9, 2017: Brazilian Journal of Microbiology: [publication of the Brazilian Society for Microbiology]
https://www.readbyqxmd.com/read/28289081/light-modulates-metabolic-pathways-and-other-novel-physiological-traits-in-the-human-pathogen-acinetobacter-baumannii
#16
Gabriela L Müller, Marisel Tuttobene, Matías Altilio, Maitena Martinez Amezaga, Meaghan Nguyen, P Pamela Cribb, Larisa E Cybulski, María Soledad Ramírez, Silvia Altabe, María Alejandra Mussi
Light sensing in chemotrophic bacteria has been relatively recently ascertained. In the human pathogen Acinetobacter baumannii, light modulates motility, biofilm formation and virulence through the BLUF photoreceptor BlsA. In addition, light can induce reduction in susceptibility to certain antibiotics such as minocycline and tigecycline in a photoreceptor-independent manner. In this work we identified new traits whose expression are modulated by light in this pathogen, which comprise not only important determinants related to pathogenicity and antibiotic resistance, but also metabolic pathways, which represents a novel concept for chemotrophic bacteria...
March 13, 2017: Journal of Bacteriology
https://www.readbyqxmd.com/read/28284195/zinc-stress-induces-copper-depletion-in-acinetobacter-baumannii
#17
Karl A Hassan, Victoria G Pederick, Liam D H Elbourne, Ian T Paulsen, James C Paton, Christopher A McDevitt, Bart A Eijkelkamp
BACKGROUND: The first row transition metal ions zinc and copper are essential to the survival of many organisms, although in excess these ions are associated with significant toxicity. Here, we examined the impact of zinc and copper stress on Acinetobacter baumannii, a common opportunistic pathogen. RESULTS: We show that extracellular zinc stress induces a copper-specific depletion phenotype in A. baumannii ATCC 17978. Supplementation with copper not only fails to rescue this phenotype, but further exacerbates the copper depletion...
March 11, 2017: BMC Microbiology
https://www.readbyqxmd.com/read/28282619/the-use-of-mrp1-deficient-danio-rerio-zebrafish-embryos-to-investigate-the-role-of-mrp1-in-the-toxicity-of-cadmium-chloride-and-benzo-a-pyrene
#18
Jingjing Tian, Jia Hu, Mingli Chen, Huancai Yin, Peng Miao, Pengli Bai, Jian Yin
Previous studies in our lab have revealed that both P-glycoprotein (Pgp) and multi-resistance associated protein (Mrp) 1 played important roles in the detoxification of heavy metals and polycyclic aromatic hydrocarbon (PAH) in zebrafish embryos. This paper aims to extend this research by using mrp1-deficient model to illustrate the individual function of Mrp1. In this respect, CRISPR/Cas9 system was employed to generate a frameshift mutation in zebrafish mrp1 causing premature translational stops in Mrp1. Significant reduction on the efflux function of Mrps was found in mutant zebrafish embryos, which correlated well with the significantly enhanced accumulation and toxicity of cadmium chloride (CdCl2) and benzo[a]pyrene (BαP), indicating the protective role of the corresponding protein...
March 2, 2017: Aquatic Toxicology
https://www.readbyqxmd.com/read/28279567/optimizing-everolimus-exposure-when-combined-with-calcineurin-inhibitors-in-solid-organ-transplantation
#19
REVIEW
Teun van Gelder, Lutz Fischer, Fuad Shihab, Maria Shipkova
The mammalian target of rapamycin (mTOR) inhibitor everolimus is a narrow therapeutic index drug for which optimal exposure levels are essential. The consistent pharmacokinetic profile of everolimus allows trough concentration (C0) measurement to be an appropriate and reliable index for therapeutic drug monitoring (TDM). Exposure-response analyses of data from early fixed-dose trials demonstrated that rates of biopsy-proven acute rejection (BPAR) are significantly higher if everolimus C0 declines below 3 ng/mL, an observation confirmed in subsequent concentration-controlled trials...
February 27, 2017: Transplantation Reviews
https://www.readbyqxmd.com/read/28275692/endoplasmic-reticulum-stress-regulates-hepatic-bile-acid-metabolism-in-mice
#20
Anne S Henkel, Brian LeCuyer, Shantel Olivares, Richard M Green
BACKGROUND & AIMS: Cholestasis promotes endoplasmic reticulum (ER) stress in the liver, however, the effect of ER stress on hepatic bile acid metabolism is unknown. We aim to determine the effect of ER stress on hepatic bile acid synthesis and transport in mice. METHODS: ER stress was induced pharmacologically in C57BL/6J mice and human hepatoma (HepG2) cells. The hepatic expression of genes controlling bile acid synthesis and transport was determined. To measure the activity of the primary bile acid synthetic pathway, the concentration of 7α-hydroxy-4-cholesten-3-1 was measured in plasma...
March 2017: Cellular and Molecular Gastroenterology and Hepatology
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