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https://www.readbyqxmd.com/read/29786944/design-synthesis-and-evaluation-of-a-novel-series-of-inhibitors-reversing-p-glycoprotein-mediated-multidrug-resistance
#1
Hesham Ghaleb, Huilan Li, Mutta Kairuki, Qianqian Qiu, Xinzhou Bi, Chunxia Liu, Chen Liao, Jieming Li, Kamal Hezam, Wenlong Huang, Hai Qian
Multidrug resistance (MDR) is still the main barrier to attaining effective results with chemotherapy. Discovery of new chemo-reversal agents is needed to overcome MDR. Our study focused on a better way to obtain novel drugs with triazole rings that have an MDR-reversal ability through click chemistry. Among 20 developed compounds, compound 19 had a minimal cytotoxic effect compared to tariquidar and verapamil (VRP) and showed a higher reversal activity than VRP through increased accumulation in K562/A02 cells...
May 22, 2018: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/29785434/integration-of-phospholipid-hyaluronic-acid-methotrexate-nanocarrier-assembly-and-amphiphilic-drug-drug-conjugate-for-synergistic-targeted-delivery-and-combinational-tumor-therapy
#2
Yang Li, Huabing Zhang, Yilin Chen, Jinyuan Ma, Jinyan Lin, Yinying Zhang, Zhongxiong Fan, Guanghao Su, Liya Xie, Xuan Zhu, Zhenqing Hou
Combinational cancer therapy has been considered as a promising strategy to achieve synergetic therapeutic effects and suppression of multidrug resistance. Herein, we adopted a combination of methotrexate (MTX), an antimetabolite acting on cytoplasm, and 10-hydroxycamptothecin (HCPT), an alkaloid acting on nuclei, to treat cancer. Given the different solubilities, membrane permeabilities, and anticancer mechanisms of both drugs, we developed a dual-targeting delivery system based on 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-hyaluronic acid (a principal ligand of CD44 receptors)-MTX (a selective ligand of folate receptors) nanoparticles, which was exploited to carry HCPT-MTX conjugate for synergistically boosting dual-drug co-delivery...
May 22, 2018: Biomaterials Science
https://www.readbyqxmd.com/read/29785129/performance-of-the-abbott-realtime-mtb-rif-inh-resistance-assay-when-used-to-test-mycobacterium-tuberculosis-specimens-from-bangladesh
#3
Joshua Kostera, Gregor Leckie, Klara Abravaya, Hong Wang
Introduction: The Abbott RealTime MTB RIF/INH Resistance Assay (RT MTB RIF/INH) is an assay for the detection of rifampicin (RIF)- and/or isoniazid (INH)-resistant Mycobacterium tuberculosis (MTB). The assay can be used to test sputum, bronchial alveolar lavage, and N-Acetyl-L-Cysteine (NALC)/NaOH pellets prepared from these samples. The assay can be used in direct testing mode, or in reflex mode following a MTB positive result produced by its companion assay, Abbott RT MTB. Methods: In this study, the direct testing mode was used to test paired sputum and NALC/NaOH pellets prepared from sputum collected from Bangladesh TB patients...
2018: Infection and Drug Resistance
https://www.readbyqxmd.com/read/29784850/molecular-analysis-of-a-bla-imp-1-harboring-class-3-integron-in-multidrug-resistant-pseudomonas-fulva
#4
Masaki Yamamoto, Yasufumi Matsumura, Ryota Gomi, Tomonari Matsuda, Satoshi Nakano, Miki Nagao, Michio Tanaka, Satoshi Ichiyama
A multidrug-resistant (MDR) Pseudomonas fulva was isolated in 2006 from a urine sample. The isolate harbored the bla IMP-1 gene, which was located in a chromosomal Tn 402 -like class 3 integron as a gene cassette array of aacA31 - fosE - bla IMP-1 Two mutations in gyrA and one mutation in parC were detected in quinolone resistance-determining regions (QRDRs). We report a full-length, novel bla IMP-1 -carrying class 3 integron. This integron and together with mutations in QRDRs could have influenced the MDR phenotypes...
May 21, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29784845/interaction-of-bacterial-phenazines-with-colistimethate-in-bronchial-epithelial-cells
#5
Valeri V Mossine, Deborah L Chance, James K Waters, Thomas P Mawhinney
Multidrug-resistant bacterial infections are being increasingly treated in clinics with polymyxins, a class of antibiotics associated with adverse effects in the kidney, nervous system, or airways of a significant proportion of human and animal patients. Although many of the resistant pathogens display enhanced virulence, a hazard of cytotoxic interactions between polymyxin antibiotics and bacterial virulence factors (VFs) has not been assessed, to date. We report here on testing paired combinations of four Pseudomonas aeruginosa VF phenazine toxins, pyocyanin (PYO), 1-hydroxyphenazine (1-HP), phenazine-1-carboxylic acid (PCA), phenazine-1-carboxamide (PCN), and two commonly prescribed polymyxin drugs, colistimethate (CMS)/colistin and polymyxin B, in three human airway cell lines, BEAS-2B, HBE-1, and CFT-1...
May 21, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29784837/the-inoculum-effect-in-the-era-of-multidrug-resistance-minor-differences-in-inoculum-have-dramatic-effect-on-minimal-inhibitory-concentration-determination
#6
Kenneth P Smith, James E Kirby
The observed MIC may depend on the number of bacteria initially inoculated into the assay. This phenomenon is termed the inoculum effect (IE) and is often most pronounced for β-lactams in strains expressing β-lactamase enzymes. The Clinical and Laboratory Standards Institute (CLSI) recommended inoculum is 5 x 105 CFU mL-1 with an acceptable range of 2-8 x 105 CFU mL-1 IE testing is typically performed using an inoculum 100-fold greater than the CLSI recommended inoculum. Therefore, it remains unknown whether the IE influences MICs during testing performed according to CLSI guidelines...
May 21, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29784578/quantitative-study-about-the-role-of-environmental-conditions-in-the-survival-capability-of-multidrug-resistant-bacteria
#7
Adrienn Hanczvikkel, Ákos Tóth
BACKGROUND: Healthcare-associated infections (HAIs) caused by multidrug-resistant bacteria (MDRB) are of global concern and hospital textiles can contribute to their transmission. MDRB are able to survive on textiles for more than enough time to spread in the environment. Some studies summarized the effect of environmental factors on the duration of bacterial survival, but it remained an open question how these factors influence the quantity of surviving bacteria in a period of a few days, which is relevant from the perspective of HAIs...
May 18, 2018: Journal of Infection and Public Health
https://www.readbyqxmd.com/read/29784273/halogenated-trimethoprim-derivatives-as-multidrug-resistant-staphylococcus-aureus-therapeutics
#8
Napon Nilchan, Wanida Phetsang, Taechin Nowwarat, Soraya Chaturongakul, Chutima Jiarpinitnun
Incorporation of halogen atoms to drug molecule has been shown to improve its properties such as enhanced in membrane permeability and increased hydrophobic interactions to its target. To investigate the effect of halogen substitutions on the antibacterial activity of trimethoprim (TMP), we synthesized a series of halogen substituted TMP and tested for their antibacterial activities against global predominant methicillin resistant Staphylococcus aureus (MRSA) strains. Structure-activity relationship analysis suggested a trend in potency that correlated with the ability of the halogen atom to facilitate in hydrophobic interaction to saDHFR...
May 19, 2018: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/29784062/multidrug-resistant-proteus-mirabilis-and-escherichia-coli-causing-fulminant-necrotising-fasciitis-a-case-report
#9
Eugene Vernyuy Yeika, Joyce Bei Foryoung, Derrick Tembi Efie, Eugene Adze Nkwetateba, Paul Nkemtendong Tolefac, Marcelin Ngowe Ngowe
BACKGROUND: Necrotizing fasciitis is a rare soft tissue infection characterized by rapid progressive necrosis with relative sparing of underlying muscles. This case is reported to highlight the emergence of multidrug resistant microbes in recent days which limits the use of empiric antibiotic therapy and necessitates early cultures and sensitivity enabling targeted antibiotic therapy. Factors that lead to antimicrobial resistance especially in sub-Saharan Africa have also been discussed...
May 21, 2018: BMC Research Notes
https://www.readbyqxmd.com/read/29783685/novel-imidazole-aldoximes-with-broad-spectrum-antimicrobial-potency-against-multidrug-resistant-gram-negative-bacteria
#10
Mirjana Skočibušić, Renata Odžak, Alma Ramić, Tomislav Smolić, Tomica Hrenar, Ines Primožič
In the search for a new class of potential antimicrobial agents, five novel N -substituted imidazole 2-aldoximes and their six quaternary salts were evaluated. The antimicrobial activity was assessed against a panel of representative Gram-positive and Gram-negative bacteria, including multidrug resistant bacteria. All compounds demonstrated potent in vitro activity against the tested microorganisms, with MIC values ranging from 6.25 to 50.0 μg/mL. Among the tested compounds, two quaternary compounds ( N -but-3-enyl- and meta - ( 10 ) or para - N -chlorobenzyl ( 11 ) imidazolium 2-aldoximes) displayed the most potent and broad-spectrum activity against both Gram-positive and Gram-negative bacterial strains...
May 18, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29783081/recent-technological-advancements-in-tuberculosis-diagnostics-a-review
#11
REVIEW
Shagun Gupta, Vipan Kakkar
Early diagnosis and on-time effective treatment are indispensable for Tuberculosis (TB) control - a life threatening infectious communicable disease. The conventional techniques for diagnosing TB normally take two to three weeks. This delay in diagnosis and further increase in detection complexity due to the emerging risks of XDR-TB (Extensively drug Resistant-TB) and MDR-TB (Multidrug Resistant-TB) are evoking interest of researchers in the field of developing rapid TB detection techniques such as biosensing and other point-of-care (POC) techniques...
May 11, 2018: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/29782954/comparison-between-disk-diffusion-and-agar-dilution-methods-to-determine-in-vitro-susceptibility-of-corynebacterium-spp-clinical-isolates-and-update-of-their-susceptibility
#12
Claudia Barberis, Eugenia Sandoval, Carlos Hernán Rodriguez, María Soledad Ramírez, Angela Famiglietti, Marisa Almuzara, Carlos Vay
INTRODUCTION: Although Corynebacterium species are part of the skin and mucous membranes microbiota, human infections caused by Corynebacterium spp. have been reported and the multidrug resistance pattern of the recovered isolates was emphasized. Due to the usefulness of disk diffusion in daily practice, the purpose of this work was to compare disk diffusion against agar dilution to determine disk diffusion breakpoints and to review the antimicrobial susceptibility of the most frequent Corynebacterium spp...
May 18, 2018: Journal of Global Antimicrobial Resistance
https://www.readbyqxmd.com/read/29782539/comparison-of-two-commercial-carbapenemase-gene-confirmatory-assays-in-multiresistant-enterobacteriaceae-and-acinetobacter-baumannii-complex
#13
Stephan Rösner, Kevin Gehlweiler, Uta Küsters, Mathias Kolbert, Kirsten Hübner, Niels Pfennigwerth, Dietrich Mack
Multidrug-resistant Gram-negative bacilli (MDR-GNB) producing carbapenemases are increasing at an alarming speed. Rapid confirmation of carbapenemase type will be an important diagnostic step in clinical microbiology laboratories not only to reduce the risk of transmissions but also for optimising antibiotic therapy in the future. We compared diagnostic reliability of two commercially available molecular assays (Check-Direct CPE vs. AID line probe assay) for detection and typing of carbapenemase genes in 80 well-characterized isolates of MDR-GNB...
2018: PloS One
https://www.readbyqxmd.com/read/29782350/effect-of-pyruvate-kinase-m2-regulating-aerobic-glycolysis-on-chemotherapy-resistance-of-estrogen-receptor-positive-breast-cancer
#14
Yuejun Qian, Lina Bi, Yingxu Yang, Dong Wang
This study aims to explore the effect and mechanism of pyruvate kinase M2 (PKM2) on chemotherapy resistance of estrogen receptor-positive breast cancer (ER BC) by regulating aerobic glycolysis. The expression of PKM2 in ER BC MCF-7 cells, T47D cells and MCF-7/ADR cells (which are subject to adriamycin/ADR induction) were determined by quantitative real-time PCR and western blot. MCF-7/ADR (M/A) cells were grouped into blank group (M/A), negative group (M/A+NC), low expression of PKM2 group (M/A+si-PKM2 group), overexpression of PKM2 group (M/A+PKM2 group) and glycolysis inhibition group (M/A+PKM2+2-DG group)...
May 18, 2018: Anti-cancer Drugs
https://www.readbyqxmd.com/read/29780364/antibacterial-efficacy-of-polysaccharide-capped-silver-nanoparticles-is-not-compromised-by-acrab-tolc-efflux-pump
#15
Mitali Mishra, Satish Kumar, Rakesh K Majhi, Luna Goswami, Chandan Goswami, Harapriya Mohapatra
Antibacterial therapy is of paramount importance in treatment of several acute and chronic infectious diseases caused by pathogens. Over the years extensive use and misuse of antimicrobial agents has led to emergence of multidrug resistant (MDR) and extensive drug resistant (XDR) pathogens. This drastic escalation in resistant phenotype has limited the efficacy of available therapeutic options. Thus, the need of the hour is to look for alternative therapeutic approaches to mitigate healthcare concerns caused due to MDR bacterial infections...
2018: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29780362/characterization-and-genomic-study-of-phage-vb_ecos-b2-infecting-multidrug-resistant-escherichia-coli
#16
Yue Xu, Xinyan Yu, Yu Gu, Xu Huang, Genyan Liu, Xiaoqiu Liu
The potential of bacteriophage as an alternative antibacterial agent has been reconsidered for control of pathogenic bacteria due to the widespread occurrence of multi-drug resistance bacteria. More and more lytic phages have been isolated recently. In the present study, we isolated a lytic phage named vB_EcoS-B2 from waste water. VB_EcoS-B2 has an icosahedral symmetry head and a long tail without a contractile sheath, indicating that it belongs to the family Siphoviridae . The complete genome of vB_EcoS-B2 is composed of a circular double stranded DNA of 44,283 bp in length, with 54...
2018: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29780361/challenges-and-promises-for-planning-future-clinical-research-into-bacteriophage-therapy-against-pseudomonas-aeruginosa-in-cystic-fibrosis-an-argumentative-review
#17
REVIEW
Martina Rossitto, Ersilia V Fiscarelli, Paola Rosati
Although early aggressive and prolonged treatment with specific antibiotics can extend survival in patients with cystic fibrosis (CF) colonized by opportunistic Pseudomonas aeruginosa (PA), antibiotics fail to eradicate the infecting multidrug-resistant (MDR) PA strains in CF. Century-long research has suggested treating patients with bacteriophages (phages, prokaryotic viruses) naturally hosted by bacteria. Although the only phage types used in therapy, lytic phages, lyse PA aggregated in biofilm matrix by depolymerase degrading enzymes, how they can effectively, safely, and persistently do so in patients with CF is unclear...
2018: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29779778/identification-of-tb-e12-as-a-novel-ftsz-inhibitor-with-anti-tuberculosis-activity
#18
Yuan Lin, Hongjuan Zhang, Ningyu Zhu, Xia Wang, Yanxing Han, Minghua Chen, Jiandong Jiang, Shuyi Si
The global pandemic of multidrug-resistant (MDR) Mycobacterium tuberculosis (TB) drives for more effective anti-TB drugs with new drug target. Filamentous temperature sensitive protein Z (FtsZ), a GTP dependent prokaryotic cell division protein, forms a dynamic Z-ring in the center of the cell. Differences between bacterial FtsZ and eukaryotic tubulin make FtsZ a highly attractive drug target. In this study, we used phenotype screening of M. smegmatis and model screening targeting M. tuberculosis FtsZ (Mtb-FtsZ) to identify a hit compound TB-E12...
May 2018: Tuberculosis
https://www.readbyqxmd.com/read/29779772/dissecting-whole-genome-sequencing-based-online-tools-for-predicting-resistance-in-mycobacterium-tuberculosis-can-we-use-them-for-clinical-decision-guidance
#19
Rita Macedo, Alexandra Nunes, Isabel Portugal, Sílvia Duarte, Luís Vieira, João Paulo Gomes
Whole-genome sequencing (WGS)-based bioinformatics platforms for the rapid prediction of resistance will soon be implemented in the Tuberculosis (TB) laboratory, but their accuracy assessment still needs to be strengthened. Here, we fully-sequenced a total of 54 multidrug-resistant (MDR) and five susceptible TB strains and performed, for the first time, a simultaneous evaluation of the major four free online platforms (TB Profiler, PhyResSE, Mykrobe Predictor and TGS-TB). Overall, the sensitivity of resistance prediction ranged from 84...
May 2018: Tuberculosis
https://www.readbyqxmd.com/read/29779771/genetic-diversity-of-mycobacterium-tuberculosis-isoniazid-monoresistant-and-multidrug-resistant-in-rio-grande-do-sul-a-tuberculosis-high-burden-state-in-brazil
#20
Leonardo Souza Esteves, Elis Regina Dalla Costa, Sidra Ezidio Gonçalves Vasconcellos, Andrei Vargas, Sérgio Luis Montego Ferreira Junior, Maria Laura Halon, Marta Osorio Ribeiro, Rodrigo Rodenbusch, Harrison Magdinier Gomes, Philip N Suffys, Maria Lucia R Rossetti
Tuberculosis (TB) remains a major public health problem in the world and Brazil is among the countries with the highest incidence and prevalence rates, and Rio Grande do Sul, a Brazilian state, occupy a prominent position. Multidrug-resistant Mycobacterium tuberculosis (MDR-TB) further aggravates this scenario, making it more difficult to treat and control the disease. Isoniazid monoresistance (IMR) may increase the risk of progression to MDR-TB and treatment failure. However, most drug resistance molecular tests only focus on detecting rifampicin (RIF) resistance...
May 2018: Tuberculosis
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