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Antibiotic Efflux

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https://www.readbyqxmd.com/read/28430673/antimicrobial-resistant-streptococcus-pneumoniae-prevalence-mechanisms-and-clinical-implications
#1
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...
April 19, 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
#2
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
#3
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...
April 13, 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
#4
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
#5
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...
April 17, 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
#6
Yinfeng Lyu, Xuan Yang, Sudeep Goswami, Bala Kishan Gorityala, Temilolu Idowu, Ronald Domalaon, George G Zhanel, Anshan Shan, Frank M 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 which sensitize Gram-negative bacteria to legacy antibiotics...
April 14, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28401467/response-of-extreme-haloarchaeon-haloarcula-argentinensis-rr10-to-simulated-microgravity-in-clinorotation
#7
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
https://www.readbyqxmd.com/read/28400529/control-of-gdhr-expression-in-neisseria-gonorrhoeae-via-autoregulation-and-a-master-repressor-mtrr-of-a-drug-efflux-pump-operon
#8
Corinne E Rouquette-Loughlin, Yaramah M Zalucki, Vijaya L Dhulipala, Jacqueline T Balthazar, Raúl G Doyle, Robert A Nicholas, Afrin A Begum, Erica L Raterman, Ann E Jerse, William M Shafer
The MtrCDE efflux pump of Neisseria gonorrhoeae contributes to gonococcal resistance to a number of antibiotics used previously or currently in treatment of gonorrhea, as well as to host-derived antimicrobials that participate in innate defense. Overexpression of the MtrCDE efflux pump increases gonococcal survival and fitness during experimental lower genital tract infection of female mice. Transcription of mtrCDE can be repressed by the DNA-binding protein MtrR, which also acts as a global regulator of genes involved in important metabolic, physiologic, or regulatory processes...
April 11, 2017: MBio
https://www.readbyqxmd.com/read/28399372/a-tobramycin-vector-enhances-synergy-and-efficacy-of-efflux-pump-inhibitors-against-multidrug-resistant-gram-negative-bacteria
#9
Xuan Yang, Sudeep Goswami, Bala Kishan Gorityala, Ronald Domalaon, Yinfeng Lyu, Ayush Kumar, George G Zhanel, Frank M Schweizer
Drug efflux mechanisms interact synergistically with the outer membrane permeability barrier of Gram-negative bacteria leading to intrinsic resistance that presents a major challenge for antibiotic drug development. Efflux pump inhibitors (EPIs) which block the efflux of antibiotics synergize antibiotics but the clinical development of EPI/antibiotic combination therapy to treat multidrug-resistant (MDR) Gram-negative infections has been challenging. This is in part caused by the inefficiency of current EPIs to penetrate the outer membrane and resist efflux...
April 11, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28396541/antibiotic-resistance-markers-in-strain-bp1651-of-burkholderia-pseudomallei-identified-by-genome-sequence-analysis
#10
Julia V Bugrysheva, David Sue, Jay E Gee, Mindy G Elrod, Alex R Hoffmaster, Linnell B Randall, Sunisa Chirakul, Apichai Tuanyok, Herbert P Schweizer, Linda M Weigel
Burkholderia pseudomallei Bp1651 is resistant to several classes of antibiotics that are usually effective for treatment of melioidosis including β-lactams such as penicillins (amoxicillin/clavulanic acid), cephalosporins (ceftazidime), carbapenems (imipenem and meropenem), as well as tetracyclines and sulfonamides. We sequenced, assembled, and annotated the Bp1651 genome, and analyzed the sequence using comparative genomic analyses with susceptible strains, keyword searches of the annotation, publicly available antimicrobial resistance prediction tools, and published reports...
April 10, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28394295/antimicrobial-resistance-and-the-alternative-resources-with-special-emphasis-on-plant-based-antimicrobials-a-review
#11
REVIEW
Harish Chandra, Parul Bishnoi, Archana Yadav, Babita Patni, Abhay Prakash Mishra, Anant Ram Nautiyal
Indiscriminate and irrational use of antibiotics has created an unprecedented challenge for human civilization due to microbe's development of antimicrobial resistance. It is difficult to treat bacterial infection due to bacteria's ability to develop resistance against antimicrobial agents. Antimicrobial agents are categorized according to their mechanism of action, i.e., interference with cell wall synthesis, DNA and RNA synthesis, lysis of the bacterial membrane, inhibition of protein synthesis, inhibition of metabolic pathways, etc...
April 10, 2017: Plants (Basel, Switzerland)
https://www.readbyqxmd.com/read/28392838/global-gene-expression-in-escherichia-coli-isolated-from-the-diseased-ocular-surface-of-the-human-eye-with-a-potential-to-form-biofilm
#12
Konduri Ranjith, Kotakonda Arunasri, Gundlapally Sathyanarayana Reddy, HariKrishna Adicherla, Savitri Sharma, Sisinthy Shivaji
BACKGROUND: Escherichia coli, the gastrointestinal commensal, is also known to cause ocular infections such as conjunctivitis, keratitis and endophthalmitis. These infections are normally resolved by topical application of an appropriate antibiotic. But, at times these E. coli are resistant to the antibiotic and this could be due to formation of a biofilm. In this study ocular E. coli from patients with conjunctivitis, keratitis or endophthalmitis were screened for their antibiotic susceptibility and biofilm formation potential...
2017: Gut Pathogens
https://www.readbyqxmd.com/read/28384185/evaluation-of-a-modified-meropenem-hydrolysis-assay-on-a-large-cohort-of-kpc-and-vim-carbapenemase-producing-enterobacteriaceae
#13
Adriana Calderaro, Mirko Buttrini, Maddalena Piergianni, Sara Montecchini, Monica Martinelli, Silvia Covan, Giovanna Piccolo, Maria Cristina Medici, Maria Cristina Arcangeletti, Carlo Chezzi, Flora De Conto
Carbapenem-resistant Enterobacteriaceae (CRE) have spread globally and represent a serious and growing threat to public health. The introduction of rapid and sensitive methods for the detection of carbapenemase-producing bacteria is of increasing importance. The carbapenemase production can be detected using non-molecular methods (such as the modified Hodge test, the synergy test, the Carba NP test and the antibiotic hydrolysis assays) and DNA-based methods. In this study, we propose a modified version of a previously described meropenem hydrolysis assay (MHA) by MALDI-TOF MS for the phenotypic detection in 2h of carbapenemase-producing Enterobacteriaceae...
2017: PloS One
https://www.readbyqxmd.com/read/28383665/a-pan-genomic-approach-to-understand-the-basis-of-host-adaptation-in-achromobacter
#14
J Jeukens, L Freschi, A T Vincent, J G Emond-Rheault, I Kukavica-Ibrulj, S J Charette, R C Levesque
Over the past decade, there has been a rising interest in Achromobacter sp., an emerging opportunistic pathogen responsible for nosocomial and cystic fibrosis (CF) lung infections. Species of this genus are ubiquitous in the environment, can outcompete resident microbiota, and are resistant to commonly used disinfectants as well as antibiotics. Nevertheless, the Achromobacter genus suffers from difficulties in diagnosis, unresolved taxonomy and limited understanding of how it adapts to the CF lung, not to mention other host environments...
April 5, 2017: Genome Biology and Evolution
https://www.readbyqxmd.com/read/28381709/structural-analysis-and-new-drug-development-against-multidrug-efflux-pumps
#15
Seiji Yamasaki, Ryosuke Nakashima, Keisuke Sakurai, Akihito Yamaguchi, Kunihiko Nishino
 Multidrug efflux pumps are important in the multidrug resistance of Gram-negative pathogens. However, despite efforts to develop efflux inhibitors, clinically useful inhibitors are not available at present. ABI-PP (a pryridopyrimidine derivative) is a MexB-specific inhibitor that does not inhibit MexY; MexB and MexY are principal pumps in Pseudomonas aeruginosa. We previously found that drugs were exported through tandem proximal and distal multisite drug-binding pockets. Here we describe the first inhibitor-bound structures of pumps...
2017: Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan
https://www.readbyqxmd.com/read/28373967/defining-the-roles-of-the-cation-diffusion-facilitators-in-fe-2-zn-2-homeostasis-and-establishment-of-their-participation-in-virulence-in-pseudomonas-aeruginosa
#16
Agostina Salusso, Daniel Raimunda
Transporters of the cation diffusion facilitator (CDF) family form dimers that export transition metals from the cytosol. The opportunistic pathogen Pseudomonas aeruginosa encodes three homologous CDF genes, czcD (PA0397), aitP (PA1297), and yiiP (PA3963). The three proteins are required for virulence in a plant host model. Disruption of the aitP gene leads to higher Fe(2+) and Co(2+) sensitivity together with an intracellular accumulation of these ions and to a decreased survival in presence of H2O2. Strains lacking czcD and yiiP showed low Zn(2+) sensitivity...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28373352/the-perr-regulated-p1b-4-type-atpase-pmta-acts-as-a-ferrous-iron-efflux-pump-in-streptococcus-pyogenes
#17
Andrew G Turner, Cheryl-Lynn Y Ong, Karrera Y Djoko, Nicholas P West, Mark R Davies, Alastair G McEwan, Mark J Walker
Streptococcus pyogenes (group A Streptococcus; GAS) is an obligate human pathogen responsible for a broad spectrum of human disease. GAS has a requirement for metal homeostasis within the human host and as such, tightly modulates metal uptake and efflux during infection. Metal acquisition systems are required to combat metal sequestration by the host, while metal efflux systems are essential to protect against metal overload poisoning. Here, we investigated the function of PmtA (PerR-regulated metal transporter A), a P1B-4 type ATPase efflux pump, in the invasive GAS M1T1 strain 5448...
April 3, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28373194/a-new-natural-product-analog-of-blasticidin-s-reveals-cellular-uptake-facilitated-by-the-nora-multidrug-transporter
#18
Jack R Davison, Katheryn M Lohith, Xiaoning Wang, Kostyantyn Bobyk, Sivakoteswara R Mandadapu, Su-Lin Lee, Regina Cencic, Justin Nelson, Scott Simpkins, Karen M Frank, Jerry Pelletier, Chad L Myers, Jeff Piotrowski, Harold E Smith, Carole A Bewley
The permeation of antibiotics through bacterial membranes to their target site is a crucial determinant of drug activity, but in many cases remains poorly understood. During screening efforts to discover new broad-spectrum antibiotic compounds from marine sponge samples, we identified a new analog of the peptidyl nucleoside antibiotic blasticidin S that exhibited up to 16-fold improved potency against a range of laboratory and clinical bacterial strains, which we named P10. Whole genome sequencing of laboratory-evolved strains of Staphylococcus aureus resistant to blasticidin S and P10, combined with genome-wide assessment of the fitness of barcoded Escherichia coli knockout strains in the presence of the antibiotics, revealed that the restriction of cellular access was a key feature in the development of resistance to this class of drug...
April 3, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28363336/active-efflux-in-dormant-bacterial-cells-new-insights-into-antibiotic-persistence
#19
Yingying Pu, Yuehua Ke, Fan Bai
Bacterial persisters are phenotypic variants of an isogenic cell population that can survive antibiotic treatment and resume growth after the antibiotics have been removed. Cell dormancy has long been considered the principle mechanism underlying persister formation. However, dormancy alone is insufficient to explain the full range of bacterial persistence. Our recent work revealed that in addition to 'passive defense' via dormancy, persister cells employ 'active defense' via enhanced efflux activity to expel drugs...
January 2017: Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
https://www.readbyqxmd.com/read/28359243/redox-biotransformation-and-delivery-of-anthracycline-anticancer-antibiotics-how-interpretable-structure-activity-relationships-of-lethality-using-electrophilicity-and-the-london-formula-for-dispersion-interaction-work
#20
Siu-Kwong Pang
Quantum chemical methods and molecular mechanics approaches face a lot of challenges in drug metabolism study because of their either insufficient accuracy or huge computational cost, or lack of clear molecular level pictures for building computational models. Low-cost QSAR methods can often be carried out even though molecular level pictures are not well defined; however, they show difficulty in identifying the mechanisms of drug metabolism and delineating the effects of chemical structures on drug toxicity because a certain amount of molecular descriptors are difficult to be interpreted...
March 30, 2017: Current Cancer Drug Targets
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