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https://www.readbyqxmd.com/read/28529506/roles-of-regulatory-rnas-for-antibiotic-resistance-in-bacteria-and-their-potential-value-as-novel-drug-targets
#1
REVIEW
Petra Dersch, Muna A Khan, Sabrina Mühlen, Boris Görke
The emergence of antibiotic resistance mechanisms among bacterial pathogens increases the demand for novel treatment strategies. Lately, the contribution of non-coding RNAs to antibiotic resistance and their potential value as drug targets became evident. RNA attenuator elements in mRNA leader regions couple expression of resistance genes to the presence of the cognate antibiotic. Trans-encoded small RNAs (sRNAs) modulate antibiotic tolerance by base-pairing with mRNAs encoding functions important for resistance such as metabolic enzymes, drug efflux pumps, or transport proteins...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28528649/metal-resistance-and-its-association-with-antibiotic-resistance
#2
Chandan Pal, Karishma Asiani, Sankalp Arya, Christopher Rensing, Dov J Stekel, D G Joakim Larsson, Jon L Hobman
Antibiotic resistance is recognised as a major global threat to public health by the World Health Organization. Currently, several hundred thousand deaths yearly can be attributed to infections with antibiotic-resistant bacteria. The major driver for the development of antibiotic resistance is considered to be the use, misuse and overuse of antibiotics in humans and animals. Nonantibiotic compounds, such as antibacterial biocides and metals, may also contribute to the promotion of antibiotic resistance through co-selection...
2017: Advances in Microbial Physiology
https://www.readbyqxmd.com/read/28525328/establishment-of-5-fluorouracil-resistant-canine-mammary-tumor-cell-line
#3
B Zhou, D Zhang, S M Pei, H Zhang, H C Du, Y P Jin, D G Lin
Canine mammary tumors are the most common neoplasms in intact female dogs. The surgery cannot always solve the problem, chemotherapy are recommend to these patients. However, chemotherapy could always fail because of multidrug resistance (MDR). Through stepwise increasing 5-Fluorouracil (5-FU) concentration in the culture medium, a 5-FU-resistant canine mammary tumor cell line CMT7364/5-FU was established to disclose the molecular mechanism of the drug resistance. Cell morphology, cell sensitivity to drugs, growth curves, expression of proteins, and chemo-sensitivity in vivo were compared between the parental cell line and resistant cell line...
March 28, 2017: Polish Journal of Veterinary Sciences
https://www.readbyqxmd.com/read/28521675/chemotherapy-with-si-rna-and-anti-cancer-drugs
#4
Kamaljeet Kaur, Goutam Rath, Saket Chandra, Ranjit Singh, Amit K Goyal
To treat cancer, chemotherapy is a key therapeutic approach which is associated with several limitations. This chemotherapeutical agents exhibit multi drug resistance coupled with undesirable side effects. This multidrug resistance is exhibited by tumor cell due to actuation of drug out flow mechanism, programmed cell death and protection mechanisms etc. One of the therapeutic approaches to cure cancer is RNA interference (RNAi). Small interfering RNA (si-RNA) is considered as a major therapeutic tool used to control expression of a particular gene...
May 18, 2017: Current Drug Delivery
https://www.readbyqxmd.com/read/28520511/upregulation-of-acref-in-quinolone-resistance-development-in-escherichia-coli-when-acrab-tolc-function-is-impaired
#5
Chuan-Zhen Zhang, Man-Xia Chang, Lei Yang, Yan-Yan Liu, Pin-Xian Chen, Hong-Xia Jiang
We studied mechanisms of drug resistance development in Escherichia coli strains lacking efflux pump components. E. coli K12 deletion mutants were subjected to increasing concentrations of ciprofloxacin (CIP) to determine the frequency of target gene mutations. We generated a series of mutants that were selected based on their minimum inhibitory concentrations (MICs) to CIP, as well as their corresponding point mutations in target genes. The mutants displayed a number of target modifications and, in particular, gyrA mutations altering codons Ser83Leu, Asp87Gly, and Asp87His as well as a change in parC at 78 (substitution of Gly for Asp)...
May 18, 2017: Microbial Drug Resistance: MDR: Mechanisms, Epidemiology, and Disease
https://www.readbyqxmd.com/read/28516210/antibiotic-resistance-genes-in-surface-water-of-eutrophic-urban-lakes-are-related-to-heavy-metals-antibiotics-lake-morphology-and-anthropic-impact
#6
Yuyi Yang, Chen Xu, Xinhua Cao, Hui Lin, Jun Wang
Urban lakes are impacted by heavy human activities and represent potential reservoirs for antibiotic resistance genes. In this study, six urban lakes in Wuhan, central China were selected to analyze the distribution of sulfonamide resistance (sul) genes, tetracycline resistance (tet) genes and quinolone resistance (qnr) genes and their relationship with heavy metals, antibiotics, lake morphology and anthropic impact. sul1 and sul2 were detected in all six lakes and dominated the types of antibiotic resistance genes, which accounted for 86...
May 17, 2017: Ecotoxicology
https://www.readbyqxmd.com/read/28516003/mode-of-action-of-the-2-phenylquinoline-efflux-inhibitor-pqq4r-against-escherichia-coli
#7
Diana Machado, Laura Fernandes, Sofia S Costa, Rolando Cannalire, Giuseppe Manfroni, Oriana Tabarrini, Isabel Couto, Stefano Sabatini, Miguel Viveiros
Efflux pump inhibitors are of great interest since their use as adjuvants of bacterial chemotherapy can increase the intracellular concentrations of the antibiotics and assist in the battle against the rising of antibiotic-resistant bacteria. In this work, we have described the mode of action of the 2-phenylquinoline efflux inhibitor (4-(2-(piperazin-1-yl)ethoxy)-2-(4-propoxyphenyl) quinolone - PQQ4R), against Escherichia coli, by studding its efflux inhibitory ability, its synergistic activity in combination with antibiotics, and compared its effects with the inhibitors phenyl-arginine-β-naphthylamide (PAβN) and chlorpromazine (CPZ)...
2017: PeerJ
https://www.readbyqxmd.com/read/28511383/study-on-mics-of-tigecycline-in-clinical-isolates-of-carbapenem-resistant-enterobacteriaceae-cre-at-a-tertiary-care-centre-in-north-india
#8
Vineeta Khare, Prashant Gupta, Fareya Haider, Rehana Begum
INTRODUCTION: Members of family Enterobacteriaceae are the most common Gram-negative bacteria isolated from clinical samples. Those Enterobacteriaceae which have acquired resistance to all β-lactams antibiotics including the carbapenems are considered as Carbapenem Resistant Enterobacteriaceae (CRE). These CRE isolates are often resistant to most other classes of antimicrobials as well, making their treatment a great challenge. Tigecycline is one of the last resort antimicrobials against such multidrug resistant bacteria...
March 2017: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28510317/efflux-pumps-may-not-be-the-major-drivers-of-qac-resistance-in-methicillin-resistant-staphylococcus-aureus
#9
Megan C Jennings, Megan E Forman, Stephanie M Duggan, Kevin P C Minbiole, William M Wuest
Quaternary ammonium compounds (QACs) are commonly used antiseptics that are now known to be subject to bacterial resistance. The prevalence and mechanisms of such resistance, however, remain underexplored. We investigated a variety of QACs, including those with multicationic structures (multiQACs), and the resistance displayed by a variety of Staphylococcus aureus strains with and without genes encoding efflux pumps, the purported main driver of bacterial resistance in MRSA. Through MIC, kinetic, and efflux-based assays, we find that neither the qacR/qacA system present in S...
May 16, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28507116/toxic-electrophiles-induce-expression-of-the-multi-drug-efflux-pump-mexef-oprn-in-pseudomonas-aeruginosa-through-a-novel-transcriptional-regulator-cmra
#10
Paulo Juarez, Katy Jeannot, Patrick Plésiat, Catherine Llanes
The multidrug efflux system MexEF-OprN is produced at low levels in wild-type strains of Pseudomonas aeruginosa. However, mutational alteration of gene mexS results in constitutive overexpression of the pump along with an increased resistance of the bacterium to chloramphenicol, fluoroquinolones and trimethoprim. In this study, analysis of in vitro selected chloramphenicol-resistant clones of strain PA14 led to the identification of a new class of mutants (called nfxC2) exhibiting alterations in a so far uncharacterized gene, PA14_38040 (homolog of PA2047 in strain PAO1)...
May 15, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28507109/erg11-gene-mutations-and-mdr1-up-regulation-confer-pan-azole-resistance-in-candida-tropicalis-causing-disseminated-candidiasis-while-on-posaconazole-prophylaxis-in-an-acute-lymphoblastic-leukemia-patient
#11
Liangshun You, Wenbin Qian, Qing Yang, Liping Mao, Li Zhu, Xianbo Huang, Jie Jin, Haitao Meng
In this study, we presented a rare case of fatal breakthrough Candida tropicalis in a patient with acute lymphoblastic leukemia (ALL) while on posaconazole prophylaxis. And then we explored the mechanisms underlying azole resistance by focusing on enhanced efflux pumps and changes in the azole target enzyme Erg11p, which was encoded by the ERG11 gene. Our study demonstrates that Y132C substitution of Erg11p combined with MDR1 overexpression may be the pan-azole-resistance mechanisms in Candida tropicalis.
May 15, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28506804/chloroquine-enhances-the-antimycobacterial-activity-of-isoniazid-and-pyrazinamide-by-reversing-inflammation-induced-macrophage-efflux
#12
U Matt, P Selchow, M Dal Molin, S Strommer, O Sharif, K Schilcher, F Andreoni, A Stenzinger, A S Zinkernagel, M Zeitlinger, P Sander, J Nemeth
Mycobacterium tuberculosis (MTB) is notorious for persisting within host macrophages. Efflux pumps decrease intracellular drug levels, thus fostering persistence of MTB during therapy. Isoniazid (INH) and pyrazinamide (PZA) are substrates of the efflux pump breast cancer resistance protein-1 (BCRP-1), which is inhibited by chloroquine (CQ). In this study, BCRP-1 was found to be expressed on macrophages of human origin and on foamy giant cells at the site of MTB infection. In the current in vitro study, interferon-gamma (IFNγ) increased the expression of BCRP-1 in macrophages derived from the human monocytic leukaemia cell line THP-1...
May 12, 2017: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/28504927/mechanisms-of-quinolone-action-and-resistance-where-do-we-stand
#13
Susana Correia, Patrícia Poeta, Michel Hébraud, José Luis Capelo, Gilberto Igrejas
Quinolone antibiotics represent one of the most important classes of anti-infective agents and, although still clinically valuable, their use has been compromised by the increasing emergence of resistant strains, which has become a prevalent clinical problem. Quinolones act by inhibiting the activity of DNA gyrase and topoisomerase IV - two essential bacterial enzymes that modulate the chromosomal supercoiling required for critical nucleic acid processes. The acquisition of quinolone resistance is recognized to be multifactorial and complex...
May 2017: Journal of Medical Microbiology
https://www.readbyqxmd.com/read/28504659/structure-of-the-macab-tolc-abc-type-tripartite-multidrug-efflux-pump
#14
Anthony W P Fitzpatrick, Salomé Llabrés, Arthur Neuberger, James N Blaza, Xiao-Chen Bai, Ui Okada, Satoshi Murakami, Hendrik W van Veen, Ulrich Zachariae, Sjors H W Scheres, Ben F Luisi, Dijun Du
The MacA-MacB-TolC assembly of Escherichia coli is a transmembrane machine that spans the cell envelope and actively extrudes substrates, including macrolide antibiotics and polypeptide virulence factors. These transport processes are energized by the ATPase MacB, a member of the ATP-binding cassette (ABC) superfamily. We present an electron cryo-microscopy structure of the ABC-type tripartite assembly at near-atomic resolution. A hexamer of the periplasmic protein MacA bridges between a TolC trimer in the outer membrane and a MacB dimer in the inner membrane, generating a quaternary structure with a central channel for substrate translocation...
May 15, 2017: Nature Microbiology
https://www.readbyqxmd.com/read/28501703/xanthohumol-a-hop-derived-prenylated-flavonoid-promotes-macrophage-reverse-cholesterol-transport
#15
Hiroshi Hirata, Harumi Uto-Kondo, Masatsune Ogura, Makoto Ayaori, Kazusa Shiotani, Ami Ota, Youichi Tsuchiya, Katsunori Ikewaki
Xanthohumol, a prominent prenyl flavonoid from the hop plant (Humulus lupulus L.), is suggested to be antiatherogenic since it reportedly increases high-density lipoprotein (HDL) cholesterol levels. It is not clear whether xanthohumol promotes reverse cholesterol transport (RCT), the most important antiatherogenic property of HDL; therefore, we investigated the effects of xanthohumol on macrophage-to-feces RCT using a hamster model as a CETP-expressing species. In vivo RCT experiments showed that xanthohumol significantly increased fecal appearance of the tracer derived from intraperitoneally injected [(3)H]-cholesterol-labeled macrophages...
April 22, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28496441/discovery-of-novel-leptospirosis-vaccine-candidates-using-reverse-and-structural-vaccinology
#16
André Alex Grassmann, Frederico Schmitt Kremer, Júlia Cougo Dos Santos, Jéssica Dias Souza, Luciano da Silva Pinto, Alan John Alexander McBride
Leptospira spp. are diderm (two membranes) bacteria that infect mammals causing leptospirosis, a public health problem with global implications. Thousands of people die every year due to leptospirosis, especially in developing countries with tropical climates. Prophylaxis is difficult due to multiple factors, including the large number of asymptomatic hosts that transmit the bacteria, poor sanitation, increasing numbers of slum dwellers, and the lack of an effective vaccine. Several leptospiral recombinant antigens were evaluated as a replacement for the inactivated (bacterin) vaccine; however, success has been limited...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28496433/interplay-between-mutations-and-efflux-in-drug-resistant-clinical-isolates-of-mycobacterium-tuberculosis
#17
Diana Machado, Tatiane S Coelho, João Perdigão, Catarina Pereira, Isabel Couto, Isabel Portugal, Raquel De Abreu Maschmann, Daniela F Ramos, Andrea von Groll, Maria L R Rossetti, Pedro A Silva, Miguel Viveiros
Numerous studies show efflux as a universal bacterial mechanism contributing to antibiotic resistance and also that the activity of the antibiotics subject to efflux can be enhanced by the combined use of efflux inhibitors. Nevertheless, the contribution of efflux to the overall drug resistance levels of clinical isolates of Mycobacterium tuberculosis is poorly understood and still is ignored by many. Here, we evaluated the contribution of drug efflux plus target-gene mutations to the drug resistance levels in clinical isolates of M...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28494730/small-molecule-efflux-pump-inhibitors-in-mycobacterium-tuberculosis-a-rational-drug-design-perspective
#18
Erika Kapp, Sarel F Malan, Samantha L Sampson
Drug resistance in Mycobacterium tuberculosis (M. tuberculosis) complicates management of tuberculosis. Efflux pumps contribute to low level resistance and acquisition of additional high level resistance mutations through sub-therapeutic concentrations of intracellular antimycobacterials. Various efflux pump inhibitors (EPIs) have been described for M. tuberculosis but little is known regarding the mechanism of efflux inhibition. As knowledge relating to the mechanism of action and drug target is central to the rational drug design of safe and sufficiently selective EPIs, this review aims to examine recent developments in the study of EPIs in M...
May 9, 2017: Mini Reviews in Medicinal Chemistry
https://www.readbyqxmd.com/read/28493713/cetuximab-prevents-methotrexate-induced-cytotoxicity-in-vitro-through-epidermal-growth-factor-dependent-regulation-of-renal-drug-transporters
#19
Pedro Caetano-Pinto, Amer Jamalpoor, Janneke Ham, Anastasia Goumenou, Monique Mommersteeg, Dirk Pijnenburg, Rob Ruijtenbeek, Natalia Sánchez-Romero, Bertrand van Zelst, Sandra Heil, Jitske Jansen, Martijn J Wilmer, Carla M L van Herpen, Rosalinde Masereeuw
The combination of methotrexate with epidermal growth factor receptor (EGFR) recombinant antibody, cetuximab, is currently being investigated in treatment of head and neck carcinoma. As methotrexate is cleared by renal excretion, we studied the effect of cetuximab on renal methotrexate handling. We used human conditionally immortalized proximal tubule epithelial cells over-expressing either organic anion transporter 1 or 3 (ciPTEC-OAT1/ciPTEC-OAT3) to examine OAT1 and OAT3, and the efflux pumps breast cancer resistance protein (BCRP), multidrug resistance protein 4 (MRP4) and P-glycoprotein (P-gp) in methotrexate handling upon EGF and/or cetuximab treatment...
May 11, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28490701/-adeabc-efflux-pump-and-resistance-of-acinetobacter-baumannii-against-carbapenem
#20
Qingya Dou, Mingxiang Zou, Jun Li, Haichen Wang, Yongmei Hu, Wen'en Liu
To investigate relationship between AdeABC efflux pump and resistance of Acinetobacter baumannii against carbapenem.
 Methods: Carbapenem-resistant strains were acquired from multistep selection resistance test by meropenem in vitro. The quantitation test for sensitivities of strains before and after induction was determined by the E-test, and carbonylcyanide-m-chlorophenylhydrazone (CCCP) inhibition test was used to screen efflux pump. PCR, sequencing analysis, or real-time PCR was used to analyze the changes of regulatory genes adeR and adeS of the AdeABC efflux pump system, or expressions of adeA, adeB, adeR, and adeS in the strains before and after induction, respectively...
April 28, 2017: Zhong Nan da Xue Xue Bao. Yi Xue Ban, Journal of Central South University. Medical Sciences
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