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Efflux pumps

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https://www.readbyqxmd.com/read/28650690/coordinated-expression-of-acrab-tolc-and-eight-other-functional-efflux-pumps-through-activating-rama-and-mara-in-salmonella-enterica-serovar-typhimurium
#1
Chuan-Zhen Zhang, Pin-Xian Chen, Lei Yang, Wan Li, Man-Xia Chang, Hong-Xia Jiang
The aim of this study was to determine the expression of eight other functional transporter genes upon acrAB inactivation and also the expression of acrAB when the function of eight other transporters are impaired in Salmonella enterica. We used single- or multigene deletion mutants (i.e., ΔacrA, ΔacrB, ΔtolC, ΔacrAB, ΔacrEF, ΔacrD, ΔmdsABC, ΔmdtABC, ΔemrAB, ΔmacAB, ΔmdfA, ΔmdtK, ΔacrABramA, ΔacrABmarA, and ΔacrABsoxS) and real time (RT)-PCR to quantify the expression of different pump and regulator genes; infection ability was characterized by adhesion and invasion assays...
June 26, 2017: Microbial Drug Resistance: MDR: Mechanisms, Epidemiology, and Disease
https://www.readbyqxmd.com/read/28650638/identification-and-structure-activity-relationships-of-novel-compounds-that-potentiate-the-activities-of-antibiotics-in-escherichia-coli
#2
Keith M Haynes, Narges Abdali, Varsha Jhawar, Helen I Zgurskaya, Jerry M Parks, Adam T Green, Jerome Yves Baudry, Valentin V Rybenkov, Jeremy C Smith, John K Walker
In Gram-negative bacteria, efflux pumps are able to prevent effective cellular concentrations from being achieved for a number of antibiotics. Small molecule adjuvants that act as efflux pump inhibitors (EPIs) have the potential to reinvigorate existing antibiotics that are currently ineffective due to efflux mechanisms. Through a combination of rigorous experimental screening and in silico virtual screening we recently identified novel classes of EPIs that interact with the membrane fusion protein AcrA, a critical component of the AcrAB-TolC efflux pump in E...
June 26, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28646205/comparative-nanouplc-ms-e-analysis-between-magainin-i-susceptible-and-resistant-escherichia-coli-strains
#3
Marlon H Cardoso, Keyla C de Almeida, Elizabete de S Cândido, André M Murad, Simoni C Dias, Octávio L Franco
In recent years the antimicrobial peptides (AMPs) have been prospected and designed as new alternatives to conventional antibiotics. Indeed, AMPs have presented great potential toward pathogenic bacterial strains by means of complex mechanisms of action. However, reports have increasingly emerged regarding the mechanisms by which bacteria resist AMP administration. In this context, we performed a comparative proteomic study by using the total bacterial lysate of magainin I-susceptible and -resistant E. coli strains...
June 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28644990/global-transcriptional-response-of-escherichia-coli-mg1655-cells-exposed-to-the-oxygenated-monoterpenes-citral-and-carvacrol
#4
Beatriz Chueca, Elisa Pérez-Sáez, Rafael Pagán, Diego García-Gonzalo
DNA microarrays were used to study the mechanism of bacterial inactivation by carvacrol and citral. After 10-min treatments of Escherichia coli MG1655 cells with 100 and 50ppm of carvacrol and citral, 76 and 156 genes demonstrated significant transcriptional differences (p≤0.05), respectively. Among the up-regulated genes after carvacrol treatment, we found gene coding for multidrug efflux pumps (acrA, mdtM), genes related to phage shock response (pspA, pspB, pspC, pspD, pspF and pspG), biosynthesis of arginine (argC, argG, artJ), and purine nucleotides (purC, purM)...
June 20, 2017: International Journal of Food Microbiology
https://www.readbyqxmd.com/read/28640746/a-chromosome-4-trisomy-contributes-to-increased-fluconazole-resistance-in-a-clinical-isolate-of-candida-albicans
#5
Matthew Z Anderson, Amrita Saha, Abid Haseeb, Richard J Bennett
Candida albicans is an important opportunistic fungal pathogen capable of causing both mucosal and disseminated disease. Infections are often treated with fluconazole, a front-line antifungal drug that targets the biosynthesis of ergosterol, a major component of the fungal cell membrane. Resistance to fluconazole can arise through a variety of mechanisms, including gain-of-function mutations, loss of heterozygosity events and aneuploidy. The clinical isolate P60002 was found to be highly resistant to azole-class drugs, yet lacked mutations or chromosomal rearrangements known to be associated with azole resistance...
June 22, 2017: Microbiology
https://www.readbyqxmd.com/read/28638412/molecular-identification-of-aminoglycoside-modifying-enzymes-and-plasmid-mediated-quinolone-resistance-genes-among-klebsiella-pneumoniae-clinical-isolates-recovered-from-egyptian-patients
#6
Mohamed F El-Badawy, Wael M Tawakol, Shaymaa W El-Far, Ibrahim A Maghrabi, Saleh A Al-Ghamdi, Moselhy S Mansy, Mohammed S Ashour, Mohamed M Shohayeb
Inappropriate use of antibiotics in clinical settings is thought to have led to the global emergence and spread of multidrug-resistant pathogens. The goal of this study was to investigate the prevalence of genes encoding aminoglycoside resistance and plasmid-mediated quinolone resistance among clinical isolates of Klebsiella pneumoniae. All K. pneumoniae isolates were phenotypically identified using API 20E and then confirmed genotypically through amplification of the specific K. pneumoniae phoE gene. All isolates were genotyped by the enterobacterial repetitive intergenic consensus polymerase chain reaction technique (ERIC-PCR)...
2017: International Journal of Microbiology
https://www.readbyqxmd.com/read/28637003/structural-recognition-of-tubulysin-b-derivatives-by-multidrug-resistance-efflux-transporters-in-human-cancer-cells
#7
Michal Stark, Yehuda G Assaraf
Multidrug resistance (MDR) is a major hindrance to curative chemotherapy of various human malignancies. Hence, novel chemotherapeutics must be evaluated for their recognition by MDR efflux transporters. Herein we explored the cytotoxic activity of synthetic tubulysin B (Tub-B, EC1009) derivatives (Tub-B-hydrazide/EC0347 and Tub-B bis-ether/EC1820), and their recognition by the MDR efflux transporters P-glycoprotein 1 (P-gp), multidrug resistance-associated protein 1 (MRP1) and breast cancer resistance protein (BCRP)...
June 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28636609/genomic-and-phenotypic-characterisation-of-fluoroquinolone-resistance-mechanisms-in-enterobacteriaceae-in-durban-south-africa
#8
John Osei Sekyere, Daniel Gyamfi Amoako
Resistance to fluoroquinolones (FQ) is being increasingly reported and found to be mediated by efflux pumps, plasmid-mediated quinolone resistance genes (PMQR) and mutations in gyrA, gyrB, parC and parE. However, studies reporting on FQ resistance mechanisms (FQRM), particularly in Africa, are focused mostly on Salmonella. This study used a whole-genome-based approach to describe FQRM in forty-eight clinical Enterobacteriaceae isolates comprising of Klebsiella pneumoniae (n = 21), Serratia marcescens (n = 12), Enterobacter spp...
2017: PloS One
https://www.readbyqxmd.com/read/28631419/the-cpxr-cpxa-system-contributes-to-salmonella-gold-resistance-by-controlling-the-gols-dependent-gesabc-transcription
#9
Sebastián Cerminati, Germán F Giri, Julián I Mendoza, Fernando C Soncini, Susana K Checa
Several regulatory systems contribute to bacterial resistance to heavy metals controlling the expression of factors required to eliminate the intoxicant and/or to repair the damage caused by it. In Salmonella, the response to Au ions is mediated by the specific metalloregulator GolS that, among other genes, controls the expression of the RND-efflux pump GesABC. In this work, we demonstrate that CpxR/CpxA, a main cell-envelope stress-responding system, promotes gesABC transcription in the presence of Au ions at neutral pH...
June 19, 2017: Environmental Microbiology
https://www.readbyqxmd.com/read/28625351/challenges-of-non-flocculating-saccharomyces-cerevisiae-haploid-strain-against-inhibitory-chemical-complex-for-ethanol-production
#10
Prihardi Kahar, Eny Ida Riyanti, Hiromi Otsuka, Hana Matsumoto, Chie Kihira, Chiaki Ogino, Akihiko Kondo
This study provides insight observation based on the gene expression and the metabolomic analysis of the natural robust yeast Saccharomyces cerevisiae NBRC849 during the fermentation in the medium containing inhibitory chemical complexes (ICC) at different concentrations. The tolerance mechanisms involved in the strain might have existed through the upregulation of genes involved in NAD(H)/NADP(H) cofactors generations (ALD6, ZWF1, GND1), membrane robustness for efflux pump (YOR1, PDR5, TPO3) and cation/polyamine transport (TPO3)...
June 15, 2017: Bioresource Technology
https://www.readbyqxmd.com/read/28623111/reversal-of-abcb1-mediated-efflux-by-imatinib-and-nilotinib-in-cells-expressing-various-transporter-levels
#11
Petr Mlejnek, Petr Kosztyu, Petr Dolezel, Susan E Bates, Eliska Ruzickova
Recently, it has been suggested that imatinib (IM) and nilotinib (NIL) could be studied beyond their original application, as inhibitors of the drug efflux pump ABCB1 (P-glycoprotein, MDR1). Since the reversal of ABCB1-mediated resistance has never been successfully demonstrated in the clinic, we addressed the question of whether IM and NIL may actually serve as efficient inhibitors of ABCB1. Here we define an efficient inhibitor as a compound that achieves full (90-100%) reversal of drug efflux at a concentration that does not exhibit significant off-target toxicity in vitro...
June 13, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28621579/optimization-of-antimicrobial-photodynamic-therapy-in-biofilms-by-inhibiting-efflux-pump
#12
Tatiana Maria Starck Fogaça de Aguiar Coletti, Laura Marise de Freitas, Ana Marisa Fusco Almeida, Carla Raquel Fontana
BACKGROUND: One of the main mechanisms of microbial resistance is given by efflux pumps, which reduce the effectiveness of antimicrobials by decreasing their intracellular concentration. OBJECTIVE AND METHODS: Considering that efflux pump inhibitors are promising adjuvant molecules for antibiotics in infections, in this study, using XTT test and colony forming unit (CFU) counting, we evaluated the association between the pump inhibitor verapamil (VP) and the antimicrobial photodynamic therapy (aPDT) mediated by methylene blue (MB) in biofilms of Escherichia coli and Staphylococcus aureus to optimize the bacterial reduction...
June 15, 2017: Photomedicine and Laser Surgery
https://www.readbyqxmd.com/read/28618136/amphiphilic-cargo-loaded-nanocarrier-enhances-antibiotic-uptake-and-perturbs-efflux-effective-synergy-for-mitigation-of-methicillin-resistant-staphylococcus-aureus
#13
Durairaj Thiyagarajan, Gopal Das, Ramesh Aiyagari
A pyridinium amphiphile-loaded Poly(lactic-co-glycolic acid) (PLGA) nanocarrier (C1-PNC) was developed as an adjuvant in order to break the resistance and restore susceptibility of methicillin-resistant Staphylococcus aureus (MRSA) cells to therapeutic antibiotics. Notably, against a clinical MRSA strain, C1-PNC could render 8 × and 6 × reduction of the minimum biofilm eradication concentration (MBEC90) of gentamicin and ciprofloxacin, respectively. Mechanistic studies on MRSA planktonic cells revealed that in case of gentamicin, C1-PNC promoted enhanced cellular uptake of the antibiotic, while the propensity of C1-PNC to inhibit efflux pump activity could be leveraged to enhance cellular accumulation of ciprofloxacin leading to effective killing of MRSA cells...
June 15, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28614259/global-regulator-soxr-is-a-negative-regulator-of-efflux-pump-gene-expression-and-affects-antibiotic-resistance-and-fitness-in-acinetobacter-baumannii
#14
Henan Li, Qi Wang, Ruobing Wang, Yawei Zhang, Xiaojuan Wang, Hui Wang
SoxR is a global regulator contributing to multidrug resistance in Enterobacteriaceae. However, the contribution of SoxR to antibiotic resistance and fitness in Acinetobacter baumannii has not yet been studied. Comparisons of molecular characteristics were performed between 32 multidrug-resistant A. baumannii isolates and 11 susceptible isolates. A soxR overexpression mutant was constructed, and its resistance phenotype was analyzed. The impact of SoxR on efflux pump gene expression was measured at the transcription level...
June 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28607072/adaptor-protein-mediates-dynamic-pump-assembly-for-bacterial-metal-efflux
#15
Ace George Santiago, Tai-Yen Chen, Lauren A Genova, Won Jung, Alayna M George Thompson, Megan M McEvoy, Peng Chen
Multicomponent efflux complexes constitute a primary mechanism for Gram-negative bacteria to expel toxic molecules for survival. As these complexes traverse the periplasm and link inner and outer membranes, it remains unclear how they operate efficiently without compromising periplasmic plasticity. Combining single-molecule superresolution imaging and genetic engineering, we study in living Escherichia coli cells the tripartite efflux complex CusCBA of the resistance-nodulation-division family that is essential for bacterial resistance to drugs and toxic metals...
June 12, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28606508/tumor-specific-delivery-of-doxorubicin-through-conjugation-of-ph-responsive-peptide-for-overcoming-drug-resistance-in-cancer
#16
Chunlai Feng, Mengjie Rui, Haijun Shen, Yuanrong Xin, Jie Zhang, Jun Li, Lixiang Yue, Wenlong Lai, Ximing Xu
The major obstacles opposed to doxorubicin (Dox) based chemotherapy are the induction of drug resistance, together with non-specific toxicities for healthy cells. In this study, we prepared a peptide-Dox conjugate aimed at offering Dox molecules a tumor-specific functionality and improving the therapeutic effects of Dox against resistant tumor cells. A slightly acidic pH-sensitive peptide (SAPSP) with high selectivity for cancer cells was attached to Dox to obtain SAPSP-Dox prodrug. The structures and properties of this prodrug were characterized, confirming several merits, including desirable pH-sensitive property, good serum stability and favorable release behavior...
June 9, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28604100/molecular-epidemiology-of-carbapenem-resistant-acinetobacter-baumannii-in-greece-an-extended-review-2000-2015
#17
Theodoros Karampatakis, Charalampos Antachopoulos, Athanassios Tsakris, Emmanuel Roilides
Carbapenem-resistant Acinetobacter baumannii (CRAB) is endemic in Greece. CRAB initially emerged in 2000 and since then, carbapenemases still have a crucial role in CRAB appearance, except for a few cases resulting from efflux pump or outer-membrane protein mechanisms. OXA-type carbapenemases present the highest prevalence worldwide and bla OXA-23-like and bla OXA-58-like are the most important genes found; VIM-yielding CRAB have also been detected, while a single CRAB isolate producing NDM has quite recently emerged in Greece...
June 12, 2017: Future Microbiology
https://www.readbyqxmd.com/read/28602804/in%C3%A2-vitro-emergence-of-fluoroquinolone-resistance-in-cutibacterium-formerly-propionibacterium-acnes-and-molecular-characterization-of-mutations-in-the-gyra-gene
#18
Eve-Marie Takoudju, Aurélie Guillouzouic, Stanimir Kambarev, Frédéric Pecorari, Stéphane Corvec
In vitro occurrence of levofloxacin (LVX) resistance in C. acnes and characterization of its molecular background were investigated. The mutation frequency was determined by inoculation of 10(8) cfu of C. acnes ATCC 11827 (LVX MIC = 0.25 mg/L) on LVX-containing agar plates. The progressive emergence of resistance was studied by a second exposure to increasing LVX concentrations. For mutants, the QRDR regions including the gyrA and parC genes were sequenced and compared to both C. acnes ATCC 11827 and C...
June 8, 2017: Anaerobe
https://www.readbyqxmd.com/read/28600147/chemoresistance-and-chemosensitization-in-cholangiocarcinoma
#19
REVIEW
Jose J G Marin, Elisa Lozano, Elisa Herraez, Maitane Asensio, Silvia Di Giacomo, Marta R Romero, Oscar Briz, Maria A Serrano, Thomas Efferth, Rocio I R Macias
One of the main difficulties in the management of patients with advanced cholangiocarcinoma (CCA) is their poor response to available chemotherapy. This is the result of powerful mechanisms of chemoresistance (MOC) of quite diverse nature that usually act synergistically. The problem is often worsened by altered MOC gene expression in response to pharmacological treatment. Since CCA includes a heterogeneous group of cancers their genetic signature coding for MOC genes is also diverse; however, several shared traits have been defined...
June 6, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28598572/searching-for-novel-inhibitors-of-the-s-aureus-nora-efflux-pump-synthesis-and-biological-evaluation-of-the-3-phenyl-1-4-benzothiazine-analogues
#20
Tommaso Felicetti, Rolando Cannalire, Maria Sole Burali, Serena Massari, Giuseppe Manfroni, Maria Letizia Barreca, Oriana Tabarrini, Bryan D Schindler, Stefano Sabatini, Glenn W Kaatz, Violetta Cecchetti
Bacterial resistance to antimicrobial agents has become an increasingly serious health problem in recent years. Among the strategies by which resistance can be achieved, overexpression of efflux pumps such as NorA of S. aureus leads to a sub-lethal concentration of the antibacterial at the active site that in turn may predispose the organism to the development of high-level target-based resistance. With the aim to improve both the chemical stability and the potency of our previously reported 3-phenyl-1,4-benzothiazine NorA inhibitors, we replaced the benzothiazine core with different nuclei...
June 9, 2017: ChemMedChem
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