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Antibiotic Efflux

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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
#1
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
#2
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/28512090/the-vibrio-cholerae-vexgh-rnd-efflux-system-maintains-cellular-homeostasis-by-effluxing-vibriobactin
#3
Dillon E Kunkle, X Renee Bina, James E Bina
Resistance-nodulation-division (RND) superfamily efflux systems have been widely studied for their role in antibiotic resistance, but their native biological functions remain poorly understood. We previously showed that loss of RND-mediated efflux in Vibrio cholerae resulted in activation of the Cpx two-component regulatory system, which mediates adaptation to stress resulting from misfolded membrane proteins. Here, we investigated the mechanism linking RND-mediated efflux to the Cpx response. We performed transposon mutagenesis screening of RND-deficient V...
May 16, 2017: MBio
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
#4
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/28504927/mechanisms-of-quinolone-action-and-resistance-where-do-we-stand
#5
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 12, 2017: Journal of Medical Microbiology
https://www.readbyqxmd.com/read/28504659/structure-of-the-macab-tolc-abc-type-tripartite-multidrug-efflux-pump
#6
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/28500348/penicillinase-resistant-antibiotics-induce-non-immune-mediated-cholestasis-through-hsp27-activation-associated-with-pkc-p38-and-pi3k-akt-signaling-pathways
#7
Audrey Burban, Ahmad Sharanek, Romain Hüe, Marion Gay, Sylvain Routier, André Guillouzo, Christiane Guguen-Guillouzo
The penicillinase-resistant antibiotics (PRAs), especially the highly prescribed flucloxacillin, caused frequent liver injury via mechanisms that remain largely non-elucidated. We first showed that flucloxacillin, independently of cytotoxicity, could exhibit cholestatic effects in human hepatocytes in the absence of an immune reaction, that were typified by dilatation of bile canaliculi associated with impairment of the Rho-kinase signaling pathway and reduced bile acid efflux. Then, we analyzed the sequential molecular events involved in flucloxacillin-induced cholestasis...
May 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28496433/interplay-between-mutations-and-efflux-in-drug-resistant-clinical-isolates-of-mycobacterium-tuberculosis
#8
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/28487172/prediction-of-vaccine-candidates-against-pseudomonas-aeruginosa-an-integrated-genomics-and-proteomics-approach
#9
Muhammad Ibrahim Rashid, Anam Naz, Amjad Ali, Saadia Andleeb
Pseudomonas aeruginosa is among top critical nosocomial infectious agents due to its persistent infections and tendency for acquiring drug resistance mechanisms. To date, there is no vaccine available for this pathogen. We attempted to exploit the genomic and proteomic information of P. aeruginosa though reverse-vaccinology approaches to unveil the prospective vaccine candidates. P. aeruginosa strain PAO1 genome was subjected to sequential prioritization approach following genomic, proteomics and structural analyses...
May 6, 2017: Genomics
https://www.readbyqxmd.com/read/28486078/characterization-of-clinically-isolated-antibiotic-resistant-salmonella-typhimurium-exposed-to-subinhibitory-concentrations-of-ceftriaxone-and-ciprofloxacin
#10
Jeongjin Kim, Juhee Ahn
This study was designed mainly to assess the phenotypic properties of clinically isolated Salmonella Typhimurium exposed to ceftriaxone and ciprofloxacin. The antibiotic susceptibility, β-lactamase activity, efflux activity, bacterial motility, biofilm-forming ability, and gene expression were determined in S. Typhimurium ATCC 19585 and S. Typhimurium CCARM 8009 when exposed to subinhibitory concentrations of ceftriaxone and ciprofloxacin. S. Typhimurium CCARM 8009 was highly resistant to ampicillin, kanamycin, penicillin G, and streptomycin, showing minimum inhibitory concentration values of more than 512 μg/ml, while S...
May 9, 2017: Microbial Drug Resistance: MDR: Mechanisms, Epidemiology, and Disease
https://www.readbyqxmd.com/read/28481346/plasticity-dynamics-and-inhibition-of-emerging-tetracycline-resistance-enzymes
#11
Jooyoung Park, Andrew J Gasparrini, Margaret R Reck, Chanez T Symister, Jennifer L Elliott, Joseph P Vogel, Timothy A Wencewicz, Gautam Dantas, Niraj H Tolia
Although tetracyclines are an important class of antibiotics for use in agriculture and the clinic, their efficacy is threatened by increasing resistance. Resistance to tetracyclines can occur through efflux, ribosomal protection, or enzymatic inactivation. Surprisingly, tetracycline enzymatic inactivation has remained largely unexplored, despite providing the distinct advantage of antibiotic clearance. The tetracycline destructases are a recently discovered family of tetracycline-inactivating flavoenzymes from pathogens and soil metagenomes that have a high potential for broad dissemination...
May 8, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28476775/defining-genetic-fitness-determinants-and-creating-genomic-resources-for-an-oral-pathogen
#12
Ajay M Narayanan, Matthew M Ramsey, Apollo Stacy, Marvin Whiteley
Periodontitis is a microbial infection that destroys the structures that support the teeth. Although typically a chronic condition, rapidly progressing, aggressive forms are associated with the oral pathogen Aggregatibacter actinomycetemcomitans One of this bacterium's key virulence traits is its ability to attach to surfaces and form robust biofilms that resist killing by the host and antibiotics. Though much has been learned about A. actinomycetemcomitans since its initial discovery, we lack insight into a fundamental aspect of its basic biology, as we do not know the full set of genes that it requires for viability (essential genome)...
May 5, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28435070/siderophores-in-clinical-isolates-of-klebsiella-pneumoniae-promote-ciprofloxacin-resistance-by-inhibiting-the-oxidative-stress
#13
Wenli Zhang, Ying Zhang, Xinxin Wang, Fengshu Ding, Yingmei Fu, Jizi Zhao, Wuqi Song, Ogutu James Opiyo, Fengmin Zhang, Xiaobei Chen
To explore the relevance of and understand the potential mechanisms behind the production of siderophores by clinical isolates of K. pneumoniae and ciprofloxacin (CIP) resistance, we divided the K. pneumoniae isolates into two groups based on bacterial siderophores productin: high siderophore-yielding group (39 strains) and low siderophore-yielding group (38 strains). The rate of CIP resistance in K. pneumoniae (27/39 = 69.23%) from the high siderophore-yielding group was significantly higher than that (16/38 = 42...
April 20, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28430673/antimicrobial-resistant-streptococcus-pneumoniae-prevalence-mechanisms-and-clinical-implications
#14
Regine Cherazard, Marcia Epstein, Thien-Ly Doan, Tanzila Salim, Sheena Bharti, Miriam A Smith
BACKGROUND: Streptococcus pneumoniae is a major cause of pneumonia, meningitis, sepsis, bacteremia, and otitis media. S. pneumoniae has developed increased resistance to multiple classes of antibiotics. STUDY DESIGN: Systematic literature review of prevalence, mechanisms, and clinical implications in S. pneumoniae resistance. AREAS OF UNCERTAINTY: Since S. pneumoniae resistance to penicillin was first reported with subsequent development of resistance to other classes of drugs, selection of appropriate antibiotic treatment is challenging...
May 2017: American Journal of Therapeutics
https://www.readbyqxmd.com/read/28428424/biased-partitioning-of-the-multidrug-efflux-pump-acrab-tolc-underlies-long-lived-phenotypic-heterogeneity
#15
Tobias Bergmiller, Anna M C Andersson, Kathrin Tomasek, Enrique Balleza, Daniel J Kiviet, Robert Hauschild, Gašper Tkačik, Călin C Guet
The molecular mechanisms underlying phenotypic variation in isogenic bacterial populations remain poorly understood. We report that AcrAB-TolC, the main multidrug efflux pump of Escherichia coli, exhibits a strong partitioning bias for old cell poles by a segregation mechanism that is mediated by ternary AcrAB-TolC complex formation. Mother cells inheriting old poles are phenotypically distinct and display increased drug efflux activity relative to daughters. Consequently, we find systematic and long-lived growth differences between mother and daughter cells in the presence of subinhibitory drug concentrations...
April 21, 2017: Science
https://www.readbyqxmd.com/read/28419231/antibiotic-resistance-in-staphylococcus-aureus-current-status-and-future-prospects
#16
Timothy J Foster
The major targets for antibiotics in staphylococci are (i) the cell envelope, (ii) the ribosome and (iii) nucleic acids. Several novel targets emerged from recent targeted drug discovery programmes including the ClpP protease and FtsZ from the cell division machinery. Resistance can either develop by horizontal transfer of resistance determinants encoded by mobile genetic elements viz plasmids, transposons and the staphylococcal cassette chromosome or by mutations in chromosomal genes. Horizontally acquired resistance can occur by one of the following mechanisms: (i) enzymatic drug modification and inactivation, (ii) enzymatic modification of the drug binding site, (iii) drug efflux, (iv) bypass mechanisms involving acquisition of a novel drug-resistant target, (v) displacement of the drug to protect the target...
May 1, 2017: FEMS Microbiology Reviews
https://www.readbyqxmd.com/read/28417918/high-prevalence-of-blandm-1-blavim-qace-and-qace%C3%AE-1-genes-and-their-association-with-decreased-susceptibility-to-antibiotics-and-common-hospital-biocides-in-clinical-isolates-of-acinetobacter-baumannii
#17
Fatma Alzahraa M Gomaa, Zeinab H Helal, Mazhar I Khan
The objective of this study was to evaluate the susceptibility of metallo-β-lactamase (MBL)-producing Acinetobacter baumannii (A. baumannii) clinical isolates to biocides. We also determined the prevalence and correlation of efflux pump genes, class 1 integron and MBL encoding genes. In addition, blaVIM, blaNDM-1, qacE and qacEΔ1 nucleotide sequence analysis was performed and compared to sequences retrieved from GenBank at the National Center for Biotechnology Information database. A. baumannii had a resistance rate to carbapenem of 71...
April 12, 2017: Microorganisms
https://www.readbyqxmd.com/read/28416660/redefining-the-essential-trafficking-pathway-for-outer-membrane-lipoproteins
#18
Marcin Grabowicz, Thomas J Silhavy
The outer membrane (OM) of Gram-negative bacteria is a permeability barrier and an intrinsic antibiotic resistance factor. Lipoproteins are OM components that function in cell wall synthesis, diverse secretion systems, and antibiotic efflux pumps. Moreover, each of the essential OM machines that assemble the barrier requires one or more lipoproteins. This dependence is thought to explain the essentiality of the periplasmic chaperone LolA and its OM receptor LolB that traffic lipoproteins to the OM. However, we show that in strains lacking substrates that are toxic when mislocalized, both LolA and LolB can be completely bypassed by activating an envelope stress response without compromising trafficking of essential lipoproteins...
May 2, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28409644/amphiphilic-tobramycin-lysine-conjugates-sensitize-multidrug-resistant-gram-negative-bacteria-to-rifampicin-and-minocycline
#19
Yinfeng Lyu, Xuan Yang, Sudeep Goswami, Bala Kishan Gorityala, Temilolu Idowu, Ronald Domalaon, George G Zhanel, Anshan Shan, Frank Schweizer
Chromosomally encoded low membrane permeability and highly efficient efflux systems are major mechanisms by which Pseudomonas aeruginosa evades antibiotic actions. Our previous reports have shown that amphiphilic tobramycin-fluoroquinolone hybrids can enhance efficacy of fluoroquinolone antibiotics against multidrug-resistant (MDR) P. aeruginosa isolates. Herein, we report on a novel class of tobramycin-lysine conjugates containing an optimized amphiphilic tobramycin-C12 tether that sensitize Gram-negative bacteria to legacy antibiotics...
May 11, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28401467/response-of-extreme-haloarchaeon-haloarcula-argentinensis-rr10-to-simulated-microgravity-in-clinorotation
#20
Rebecca Thombre, Vinaya Shinde, Jyotsana Dixit, Sagar Jagtap, Pandit B Vidyasagar
Gravity is the fundamental force that may have operated during the evolution of life on Earth. It is thus important to understand as to what the effects of gravity are on cellular life. The studies related to effect of microgravity on cells may provide greater insights in understanding of how the physical force of gravity shaped life on Earth. The present study focuses on a unique group of organisms called the Haloarchaea, which are known for their extreme resistance to survive in stress-induced environments...
May 2017: 3 Biotech
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