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https://www.readbyqxmd.com/read/28340510/the-diverse-family-of-mmpl-transporters-in-mycobacteria-from-regulation-to-antimicrobial-developments
#1
REVIEW
Albertus Viljoen, Violaine Dubois, Fabienne Girard-Misguich, Mickael Blaise, Jean-Louis Herrmann, Laurent Kremer
Mycobacterial genomes contain large sets of loci encoding membrane proteins that belong to a family of multidrug resistance pumps designated Resistance-Nodulation-Cell Division (RND) permeases. Mycobacterial membrane protein Large (MmpL) transporters represent a subclass of RND transporters known to participate in the export of lipid components across the cell envelope. These surface-exposed lipids with unusual structures play key roles in the physiology of mycobacteria and/or can act as virulence factors and immunomodulators...
March 24, 2017: Molecular Microbiology
https://www.readbyqxmd.com/read/28340411/synthesis-and-biological-evaluation-of-novel-chalcone-derivatives-as-a-new-class-of-microtubule-destabilizing-agents
#2
Xiaochao Huang, Rizhen Huang, Lingxue Li, Shaohua Gou, Hengshan Wang
A series of novel chalcone derivatives were designed and synthesized as potential antitumor agents. Structures of target molecules were confirmed by (1)H NMR, (13)C NMR and HR-MS, and evaluated for their in vitro anti-proliferative activities using MTT assay. Among them, compound 12k displayed potent activity against the test tumor cell lines including multidrug resistant human cancer lines, with the IC50 values ranged from 3.75 to 8.42 μM. In addition, compound 12k was found to induce apoptosis in NCI-H460 cells via the mitochondrial pathway, including an increase of the ROS level, loss of mitochondrial membrane potential, release of cytochrome c, down-regulation of Bcl-2, up-regulation of Bax, activation of caspase-9 and caspase-3, respectively...
March 18, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28340408/ongoing-evolution-of-pseudomonas-aeruginosa-pao1-sublines-complicates-studies-of-dna-damage-repair-and-tolerance
#3
Julia Sidorenko, Tatjana Jatsenko, Maia Kivisaar
Sublines of the major P. aeruginosa reference strain PAO1 are derivatives of the original PAO1 isolate, which are maintained in laboratories worldwide. These sublines display substantial genomic and phenotypic variation due to ongoing microevolution. Here, we examined four sublines, MPAO1, PAO1-L, PAO1-DSM and PAO1-UT, originated from different laboratories, and six DNA polymerase-deficient mutants from the P. aeruginosa MPAO1 transposon library for their employment in elucidation of DNA damage repair and tolerance mechanisms in P...
March 16, 2017: Mutation Research
https://www.readbyqxmd.com/read/28339695/incidence-and-outcomes-of-infections-caused-by-multidrug-resistant-enterobacteriaceae-in-children-2007-2015
#4
Sharon B Meropol, Allison A Haupt, Sara M Debanne
Background.: The escalating incidence of invasive disease caused by multidrug-resistant Gram-negative enteric Enterobacteriaceae (MDR-GNE) is a global concern. Scant published studies in which the epidemiology of these infections in children is described exist; previous studies focused mainly on adults, described circumscribed populations, or lacked clinical detail. The objective of this study was to examine and describe the incidence, risk factors, and outcomes associated with MDR-GNE infection in children...
February 22, 2017: Journal of the Pediatric Infectious Diseases Society
https://www.readbyqxmd.com/read/28339465/comparative-accuracy-of-the-reba-mtb-mdr-and-hain-mtbdrplus-line-probe-assays-for-the-detection-of-multidrug-resistant-tuberculosis-a-multicenter-non-inferiority-study
#5
Joshua Havumaki, Doris Hillemann, Nazir Ismail, Shaheed Vally Omar, Sophia B Georghiou, Samuel G Schumacher, Catharina Boehme, Claudia M Denkinger
INTRODUCTION: Despite recent diagnostic advances, the majority of multidrug-resistant tuberculosis (MDR-TB) cases remain undiagnosed. Line probes assays (LiPAs) hold great promise to curb the spread of MDR-TB as they can rapidly detect MDR-TB even when laboratory infrastructure is limited, yet few of these assays are currently widely available or supported by World Health Organization (WHO) policy. METHODS: The aim of this prospective, blinded, non-inferiority study was to compare the performance of YD Diagnostics REBA MTB MDR LiPA (YD) to the WHO-endorsed Hain MTBDRplus V1 LiPA (Hain V1) for the detection of rifampicin and isoniazid resistance...
2017: PloS One
https://www.readbyqxmd.com/read/28338827/strategies-for-halting-the-rise-of-multidrug-resistant-tb-epidemics-assessing-the-effect-of-early-case-detection-and-isolation
#6
Aquino L Espindola, Marie Varughese, Marek Laskowski, Affan Shoukat, Jane M Heffernan, Seyed M Moghadas
Background: The increasing rates of multidrug resistant TB (MDR-TB) have posed the question of whether control programs under enhanced directly observed treatment, short-course (DOTS-Plus) are sufficient or implemented optimally. Despite enhanced efforts on early case detection and improved treatment regimens, direct transmission of MDR-TB remains a major hurdle for global TB control. Methods: We developed an agent-based simulation model of TB dynamics to evaluate the effect of transmission reduction measures on the incidence of MDR-TB...
March 7, 2017: International Health
https://www.readbyqxmd.com/read/28337780/mechanisms-of-resistance-of-salmonella-typhimurium-to-quinolones-in-infectious-diarrhea
#7
Jing Yuan, Wei Guo
This study investigated the mechanisms of resistance of 36 quinolone-resistant Salmonella Typhimurium strains isolated from outpatients with infectious diarrhea in Beijing Tian Tan Hospital between 2013 and 2015. We measured the resistance spectrum of the 36 strains using the broth dilution method. The analysis also investigated Class 1 integrons harboring the β-lactamase gene and mutations in quinolone resistance determining regions. All 36 quinolone-resistant Salmonella Typhimurium strains were shown to be multidrug-resistant and the majority of these strains harbored Class 1 integrons...
March 24, 2017: Microbiology and Immunology
https://www.readbyqxmd.com/read/28337665/effect-of-efflux-transporter-inhibition-on-the-distribution-of-fluconazole-in-the-rat-brain
#8
Wei Wang, Na Zheng, Jiatang Zhang, Xusheng Huang, Shengyuan Yu
Multidrug resistance-associated proteins (MRPs) and organic anion transporters (OATs) are expressed on the blood-brain barrier (BBB) and blood-cerebrospinal fluid barrier (BCSFB), preventing the entry of or the pumping out of numerous molecules. Fluconazole is widely used to treat fungal meningoencephalitis. The effect of these transporters on the distribution of fluconazole in the brain is unclear. We used microdialysis to compare the distribution of fluconazole in the rat brain with and without co-administration of probenecid, a MRP and OAT inhibitor...
March 24, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28337331/light-regulated-no-release-as-a-novel-strategy-to-overcome-doxorubicin-multidrug-resistance
#9
Konstantin Chegaev, Aurore Fraix, Elena Gazzano, Gamal Eldein F Abd-Ellatef, Marco Blangetti, Barbara Rolando, Sabrina Conoci, Chiara Riganti, Roberta Fruttero, Alberto Gasco, Salvatore Sortino
Nitric oxide (NO) release from a suitable NO photodonor (NOP) can be fine-tuned by visible light stimuli at doses that are not toxic to cells but that inhibit several efflux pumps; these are mainly responsible for the multidrug resistance of the anticancer agent doxorubicin (DOX). The strategy may thus increase DOX toxicity against resistant cancer cells. Moreover, a novel molecular hybrid covalently joining DOX and NOP showed similar increased toxicity toward resistant cancer cells and, in addition, lower cardiotoxicity than DOX...
March 9, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28337086/pediatric-antimicrobial-stewardship-programs
#10
Kristen Nichols, Sylvia Stoffella, Rachel Meyers, Jennifer Girotto
The frequent use of antimicrobials in pediatric patients has led to a significant increase in multidrug-resistant bacterial infections among children. Antimicrobial stewardship programs have been created in many hospitals in an effort to curtail and optimize the use of antibiotics. Pediatric-focused programs are necessary because of the differences in antimicrobial need and use among this patient population, unique considerations and dosing, vulnerability for resistance due to a lifetime of antibiotic exposure, and the increased risk of adverse events...
January 2017: Journal of Pediatric Pharmacology and Therapeutics: JPPT: the Official Journal of PPAG
https://www.readbyqxmd.com/read/28336597/draft-genome-sequence-of-providencia-stuartii-ps71-a-multidrug-resistant-strain-associated-with-nosocomial-infections-in-greece
#11
A Liakopoulos, O Oikonomou, D W Wareham
Providencia stuartii is frequently associated with nosocomial outbreaks and displays intrinsic resistance to many commonly used antimicrobials. We report here the draft genome sequence of a P. stuartii strain carrying acquired resistance genes conferring panresistance to cephalosporins (blaSHV-5 and blaVEB-1), carbapenems (blaVIM-1), and aminoglycosides (rmtB) involved in an outbreak in Greek hospitals.
March 23, 2017: Genome Announcements
https://www.readbyqxmd.com/read/28336326/oxidative-stress-and-genes-regulation-of-cerebral-malaria-upon-zizyphus-spina-christi-treatment-in-a-murine-model
#12
Murad A Mubaraki, Taghreed A Hafiz, Saleh Al-Quraishy, Mohamed A Dkhil
The development and spread of multidrug-resistant strains of malarial parasites have led to an overwhelming increase in the resistance to current antimalarial drugs. The urgent need for alternative antimalarial drugs has directed some of the current studies toward folkloric medicine approaches. Interestingly, the Zizyphus spina Cristi leaf extract (ZLE) has been found to exhibit antiplasmodial activity. This study evaluated the protective effect of ZLE against Plasmodium berghei-induced cerebral tissue injuries in mice...
March 21, 2017: Microbial Pathogenesis
https://www.readbyqxmd.com/read/28336312/old-antibiotics-for-emerging-multidrug-resistant-extensively-drug-resistant-tuberculosis-mdr-xdr-tb
#13
Philippe Brouqui, Fanny Quenard, Michel Drancourt
Recently, multidrug-resistant tuberculosis (MDR-TB) has become a therapeutic challenge. In addition to drug resistance, drug adverse events, intravenous delivery, cost and availability of some antibiotics in low-income countries have led to a look back to old drugs, especially those efficient against closely related organisms such as Mycobacterium leprae. Here we review the available drugs that respect the conditions above and could be upgraded to first-line therapy for treating MDR-TB and extensively drug-resistant tuberculosis (XDR-TB)...
March 21, 2017: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/28336136/antimicrobial-susceptibility-of-2906-pseudomonasaeruginosa-clinical-isolates-obtained-from-patients-in-canadian-hospitals-over-a-period-of-8-years-results-of-the-canadian-ward-surveillance-study-canward-2008-2015
#14
Andrew Walkty, Philippe Lagace-Wiens, Heather Adam, Melanie Baxter, James Karlowsky, Michael R Mulvey, Melissa McCracken, George G Zhanel
Pseudomonas aeruginosa is an important nosocomial pathogen. The purpose of this study was to evaluate the antimicrobial susceptibility profile of P. aeruginosa clinical isolates obtained from inpatients and outpatients at hospitals across Canada from January 2008 to December 2015 (CANWARD Study). Susceptibility testing was performed using broth microdilution, as described by the Clinical and Laboratory Standards Institute. In total, 2906 P. aeruginosa isolates were evaluated. The percentage of isolates susceptible to common antipseudomonal antimicrobials was: colistin 94...
January 2017: Diagnostic Microbiology and Infectious Disease
https://www.readbyqxmd.com/read/28335802/use-of-low-dose-computed-tomography-to-assess-pulmonary-tuberculosis-among-healthcare-workers-in-a-tuberculosis-hospital
#15
Wei He, Bu-Dong Chen, Yan Lv, Zhen Zhou, Jin-Ping Xu, Ping-Xin Lv, Xin-Hua Zhou, Feng-Gang Ning, Cheng-Hai Li, Dong-Po Wang, Jie Zheng
BACKGROUND: According to the World Health Organization, China is one of 22 countries with serious tuberculosis (TB) infections and one of the 27 countries with serious multidrug-resistant TB strains. Despite the decline of tuberculosis in the overall population, healthcare workers (HCWs) are still at a high risk of infection. Compared with high-income countries, the TB prevalence among HCWs is higher in low- and middle-income countries. Low-dose computed tomography (LDCT) is becoming more popular due to its superior sensitivity and lower radiation dose...
March 24, 2017: Infectious Diseases of Poverty
https://www.readbyqxmd.com/read/28335779/activity-of-amp2041-against-human-and-animal-multidrug-resistant-pseudomonas-aeruginosa-clinical-isolates
#16
Clotilde Silvia Cabassi, Andrea Sala, Davide Santospirito, Giovanni Loris Alborali, Edoardo Carretto, Giovanni Ghibaudo, Simone Taddei
BACKGROUND: Antimicrobial resistance is a growing threat to public health. Pseudomonas aeruginosa is a relevant pathogen causing human and animal infections, frequently displaying high levels of resistance to commonly used antimicrobials. The increasing difficulty to develop new effective antibiotics have discouraged investment in this area and only a few new antibiotics are currently under development. An approach to overcome antibiotic resistance could be based on antimicrobial peptides since they offer advantages over currently used microbicides...
March 23, 2017: Annals of Clinical Microbiology and Antimicrobials
https://www.readbyqxmd.com/read/28335655/the-therapeutic-potential-of-targeting-abc-transporters-to-combat-multi-drug-resistance
#17
Piyush Bugde, Riya Biswas, Fabrice Merien, Jun Lu, Dong-Xu Liu, Mingwei Chen, Shufeng Zhou, Yan Li
Most disseminated cancers remain fatal despite the availability of a variety of conventional and novel treatments including surgery, chemotherapy, radiotherapy, immunotherapy, and biologically targeted therapy. A major factor responsible for the failure of chemotherapy in the treatment of cancer is the development of multidrug resistance (MDR). The overexpression of various ABC transporters in cancer cells can efficiently remove the anticancer drug from the cell, thus causing the drug to lose its effect. Areas covered: In this review, we summarised the ongoing research related to the mechanism, function, and regulation of ABC transporters...
March 24, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/28334251/isolation-of-vibrionaceae-from-wild-blue-mussel-mytilus-edulis-adults-and-their-impact-on-blue-mussel-larviculture
#18
Mieke Eggermont, Peter Bossier, Gde Sasmita Julyantoro Pande, Vyshal Delahaut, Ali Md Rayhan, Nipa Gupta, Shikder Saiful Islam, Elsie Yumo, Nancy Nevejan, Patrick Sorgeloos, Bruno Gomez-Gil, Tom Defoirdt
The blue mussel (Mytilus edulis) is known as a robust mollusk species, although its larviculture appears to be highly susceptible to diseases. In this study, we isolated 17 strains from induced mortality events in healthy wild-caught blue mussel adults and demonstrated that they caused between 17 and 98% mortality in blue mussel larvae in a newly developed, highly controlled immersion challenge test model. Eight of the isolates belong to the Splendidus clade of vibrios, while the other isolates belong to the genus Photobacterium...
March 15, 2017: FEMS Microbiology Ecology
https://www.readbyqxmd.com/read/28334036/multidrug-resistant-tuberculosis-in-prisons-located-in-former-soviet-countries-a-systematic-review
#19
Maxwell Droznin, Allen Johnson, Asal Mohamadi Johnson
BACKGROUND: A systematic literature review was performed to investigate the occurrence of multidrug-resistant tuberculosis (MDR TB) in prisons located in countries formerly part of the Soviet Union. METHODS: A systematic search of published studies reporting MDR TB occurrence in prisons located in former Soviet countries was conducted by probing PubMed and Cumulative Index Nursing and Allied Health Literature for articles that met predetermined inclusion criteria...
2017: PloS One
https://www.readbyqxmd.com/read/28333459/6-oh-phenanthroquinolizidine-alkaloid-and-its-derivatives-exert-potent-anticancer-activity-by-delaying-s-phase-progression
#20
Yuxiu Liu, Lihua Qing, Chuisong Meng, Jiajie Shi, Yan Yang, Ziwen Wang, Guifang Han, Yi Wang, Jian Ding, Ling-Hua Meng, Qingmin Wang
To discover new phenanthroindolizidine and phenanthroquinolizidine alkaloids as potential anticancer drug candidates, non-natural 6-O-desmethylcryptopleurine (2) and its derivatives were prepared. Most of the new compounds exhibited potent antiproliferative activity against A549 and BEL-7402 cells, with the lowest IC50 being 3 nM. Optically pure 2-R was further evaluated against a panel of 30 cancer cell lines and found to inhibit the proliferation of all tested cell lines, including three multidrug-resistant cell lines, with an average IC50 value of 2...
March 23, 2017: Journal of Medicinal Chemistry
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