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https://www.readbyqxmd.com/read/28644573/characteristics-of-integrons-and-associated-gene-cassettes-in-antibiotic-resistant-escherichia-coli-isolated-from-free-ranging-food-animals-in-china
#1
Mujeeb Ur Rehman, Hui Zhang, Shucheng Huang, Muhammad Kashif Iqbal, Khalid Mehmood, Houqiang Luo, Jiakui Li
We investigated the occurrence of integrons in antibiotic-resistant Escherichia coli strains isolated from free-ranging food animals, including yaks, piglets, and chickens, in China, and characterized the gene cassettes harbored within the integrons. We examined 432 E. coli strains that exhibited resistance to at least one class of antibiotics. Integrase genes and associated gene cassettes were characterized by polymerase chain reaction (PCR) analysis, restriction fragment-length polymorphism, DNA sequencing, conjugation experiments, and plasmid analysis...
June 23, 2017: Journal of Food Science
https://www.readbyqxmd.com/read/28641707/analysis-of-transmitted-hiv-drug-resistance-from-2005-to-2015-in-victoria-australia-a-comparison-of-the-old-and-the-new
#2
Jodie D'Costa, Megan Gooey, Nicole Richards, Rizmina Sameer, Elaine Lee, Doris Chibo
Background: Baseline genotyping is part of standard-of-care treatment. It reveals that transmitted drug resistance (TDR) continues to be important for the management of HIV infection. Attention is typically focused on determining whether resistance to the protease inhibitors (PI) and reverse transcriptase inhibitors (RTI) occurs. However, the increasing use of integrase inhibitors (INIs) raises a concern that TDR to this class of antiretroviral drug may also occur. Methods: PI and RTI drug resistance genotyping was performed on blood samples collected between 2005 and 2015 from 772 treatment-naïve Victorian patients infected with HIV within the previous 12 months...
June 23, 2017: Sexual Health
https://www.readbyqxmd.com/read/28641512/molecular-docking-and-molecular-dynamics-simulation-based-approach-to-explore-the-dual-inhibitor-against-hiv-1-reverse-transcriptase-and-integrase
#3
Subhash Chander, Rajan Kumar Pandey, Ashok Penta, Bhanwar Singh Choudhary, Manish Sharma, Ruchi Malik, Vijay Kumar Prajapati, Sankaranarayanan Murugesan
HIV integrase (IN) and reverse transcriptase (RT) are key enzymes for the replication of HIV-1. DNA polymerase and ribonuclease H (RNase H) are the two catalytic domains of HIV-1 RT which are validated as drug targets because of their essence for replication. IN and RNase H domain of RT share the striking structural similarity; it contains conserved DDE triad (two aspartates and one glutamate) and a pair of divalent Mg2+/Mn2+ ions at their catalytic core domain. Therefore, the search of compounds with dual inhibition of IN and RNase H can be the viable and more efficacious approach for the drug development against both wild and drug resistance strains of HIV...
June 15, 2017: Combinatorial Chemistry & High Throughput Screening
https://www.readbyqxmd.com/read/28638312/in-silico-signature-prediction-modeling-in-cytolethal-distending-toxin-producing-escherichia-coli-strains
#4
Maryam Javadi, Mana Oloomi, Saeid Bouzari
In this study, cytolethal distending toxin (CDT) producer isolates genome were compared with genome of pathogenic and commensal Escherichia coli strains. Conserved genomic signatures among different types of CDT producer E. coli strains were assessed. It was shown that they could be used as biomarkers for research purposes and clinical diagnosis by polymerase chain reaction, or in vaccine development. cdt genes and several other genetic biomarkers were identified as signature sequences in CDT producer strains...
June 2017: Genomics & Informatics
https://www.readbyqxmd.com/read/28637235/monotherapy-with-either-dolutegravir-or-raltegravir-fails-to-durably-suppress-hiv-viraemia-in-humanized-mice
#5
Alonso Heredia, Said Hassounah, Sandra Medina-Moreno, Juan C Zapata, Nhut M Le, Yingshan Han, James S Foulke, Charles Davis, Joseph Bryant, Robert R Redfield, Mark A Wainberg
Objectives: To compare the effectiveness of HIV integrase inhibitor monotherapy between raltegravir and dolutegravir as an approach to simplify therapy. Methods: We evaluated and compared the efficacy of 20 week monotherapy with dolutegravir or raltegravir in humanized mice (HSC-NSG) infected with HIV BaL . Plasma HIV RNA was measured by quantitative RT-PCR (limit of detection of 150 copies/45 μL of plasma) and drug levels by LC-MS/MS. Escape viruses were genotyped and analysed for replication capacity and drug susceptibility in tissue culture...
June 13, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28634805/comparative-prevalence-of-escherichia-coli-carrying-virulence-genes-and-class-1-and-2-integrons-in-sub-tropical-and-cool-temperate-freshwater
#6
Jatinder P S Sidhu, Paul Jagals, Amy Smith, Simon Toze
Aquatic environments are now recognized secondary habitat of potentially pathogenic Escherichia coli. In this study, PCR-based analyses were used to determine the phylogenetic composition and frequency of occurrence of eight clinically significant virulence genes (VGs) in E. coli isolates from sub-tropical Brisbane and cool temperate Tasmania freshwater in Australia. In Brisbane, non-commensal E. coli isolates belonging to the B2 and D phylogenetic group were dominant (72%). A significantly higher number (P < 0...
June 21, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/28628615/flipping-chromosomes-in-deep-sea-archaea
#7
Matteo Cossu, Catherine Badel, Ryan Catchpole, Danièle Gadelle, Evelyne Marguet, Valérie Barbe, Patrick Forterre, Jacques Oberto
One of the major mechanisms driving the evolution of all organisms is genomic rearrangement. In hyperthermophilic Archaea of the order Thermococcales, large chromosomal inversions occur so frequently that even closely related genomes are difficult to align. Clearly not resulting from the native homologous recombination machinery, the causative agent of these inversions has remained elusive. We present a model in which genomic inversions are catalyzed by the integrase enzyme encoded by a family of mobile genetic elements...
June 19, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28628528/increased-persistence-of-initial-treatment-for-hiv-infection-with-modern-antiretroviral-therapy
#8
Thibaut Davy-Mendez, Joseph J Eron, Oksana Zakharova, David A Wohl, Sonia Napravnik
BACKGROUND: Initiating antiretroviral therapy (ART) early improves clinical outcomes and prevents transmission. Guidelines for first-line therapy have changed with the availability of newer ART agents. In this study, we compared persistence and virologic response to initial ART according to the class of anchor agent used. SETTING: An observational clinical cohort study in the Southeastern United States. METHODS: All HIV-infected patients participating in the UNC Center for AIDS Research Clinical Cohort (UCHCC) and initiating ART between 1996 and 2014 were included...
June 15, 2017: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/28627771/clinical-experience-with-the-integrase-inhibitors-dolutegravir-and-elvitegravir-in-hiv-infected-patients-efficacy-safety-and-tolerance
#9
Purificación Cid-Silva, Josep María Llibre, Noelia Fernández-Bargiela, Luis Margusino-Framiñán, Vanesa Balboa-Barreiro, Berta Pernas-Souto, Isabel Martín-Herranz, Ángeles Castro-Iglesias, Eva Poveda-López
Two integrase inhibitors (INSTIs), Dolutegravir (DTG) and Elvitegravir/Cobicistat (EVG/COBI) have joined recently the pharmacotherapy arsenal against HIV. This study evaluated the efficacy and tolerability of these INSTIs in the last two years. A retrospective observational study in patients who started DTG or EVG/COBI from January 2015 to January 2017 at a reference hospital in Northwestern Spain was done. Epidemiological, clinical and immunovirological data were recorded. A statistical analysis was performed using SPSS software...
June 19, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28624199/engineering-next-generation-bet-independent-mlv-vectors-for-safer-gene-therapy
#10
Sara El Ashkar, Dominique Van Looveren, Franziska Schenk, Lenard S Vranckx, Jonas Demeulemeester, Jan De Rijck, Zeger Debyser, Ute Modlich, Rik Gijsbers
Retroviral vectors have shown their curative potential in clinical trials correcting monogenetic disorders. However, therapeutic benefits were compromised due to vector-induced dysregulation of cellular genes and leukemia development in a subset of patients. Bromodomain and extraterminal domain (BET) proteins act as cellular cofactors that tether the murine leukemia virus (MLV) pre-integration complex to host chromatin via interaction with the MLV integrase (IN) and thereby define the typical gammaretroviral integration distribution...
June 16, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28615207/allosteric-hiv-1-integrase-inhibitors-lead-to-premature-degradation-of-the-viral-rna-genome-and-integrase-in-target-cells
#11
Michaela K Madison, Dana Q Lawson, Jennifer Elliott, Ayşe Naz Ozantürk, Pratibha C Koneru, Dana Townsend, Manel Errando, Mamuka Kvaratskhelia, Sebla B Kutluay
Recent evidence indicates that inhibition of HIV-1 integrase (IN) binding to the viral RNA genome by allosteric integrase inhibitors (ALLINIs) or through mutations within IN yields aberrant particles, in which the viral ribonucleoprotein complexes (vRNPs) are eccentrically localized outside the capsid lattice. These particles are non-infectious and blocked at an early reverse transcription stage in target cells. However, the basis of this reverse transcription defect is unknown. Here we show that the viral RNA genome and IN from ALLINI-treated virions are prematurely degraded in target cells, whereas reverse transcriptase remains active and stably associated with the capsid lattice...
June 14, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28611213/spacer-capture-and-integration-by-a-type-i-f-cas1-cas2-3-crispr-adaptation-complex
#12
Robert D Fagerlund, Max E Wilkinson, Oleg Klykov, Arjan Barendregt, F Grant Pearce, Sebastian N Kieper, Howard W R Maxwell, Angela Capolupo, Albert J R Heck, Kurt L Krause, Mihnea Bostina, Richard A Scheltema, Raymond H J Staals, Peter C Fineran
CRISPR-Cas adaptive immune systems capture DNA fragments from invading bacteriophages and plasmids and integrate them as spacers into bacterial CRISPR arrays. In type I-E and II-A CRISPR-Cas systems, this adaptation process is driven by Cas1-Cas2 complexes. Type I-F systems, however, contain a unique fusion of Cas2, with the type I effector helicase and nuclease for invader destruction, Cas3. By using biochemical, structural, and biophysical methods, we present a structural model of the 400-kDa Cas14-Cas2-32 complex from Pectobacterium atrosepticum with bound protospacer substrate DNA...
June 13, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28610923/l368f-v408f-double-mutant-of-ibd-of-ledgf-p75-retains-interaction-with-m178i-mutant-of-hiv-1-integrase
#13
Anu George, Nidhanapati K Raghavendra
Lens-epithelium-derived-growth factor (LEDGF/p75) is an essential host protein for integration of HIV-1 DNA into host genome. Earlier alanine scanning mutational analysis has revealed that residues I365, D366 and F406 in the integrase binding domain (IBD) of p75 are critical for interaction with HIV-1 integrase (IN), while K364, V408 have intermediate effect and residues N367, L368, R405, K407 show wild type binding with IN. To gain insight into contribution of side chains of L368 and V408 that are adjacent to critical residues I365 and F406, respectively, site directed mutation of these residues to Ile/Leu, Met and Phe has been performed and characterized in this study...
June 10, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28608126/complete-genome-sequence-of-halomonas-ventosae-virulent-halovirus-qhhsv-1
#14
Chaoqun Fu, Qin Zhao, Zhiying Li, Yongxia Wang, Shiying Zhang, Yonghong Lai, Wei Xiao, Xiaolong Cui
A virulent halovirus QHHSV-1 which lyses Halomonas ventosae QH52-2 originating from the Qiaohou salt mine in Yunnan, Southwest China was characterized. The complete genome of QHHSV-1 is composed of a circular double-stranded DNA of 37,270 base pairs in length, with 66.8% G+C content and 69 putative open reading frames (ORFs), which were classified into five functional groups, including morphogenesis, replication/regulation, packaging, lysis and lysogeny. A putative Cro repressor gene and an integrase gene were found in the genome, showing that QHHSV-1 may utilize a lambda-like repression system under unfavorable conditions...
June 12, 2017: Archives of Virology
https://www.readbyqxmd.com/read/28605418/should-we-be-testing-for-baseline-integrase-resistance-in-patients-newly-diagnosed-with-hiv
#15
Yiannis Koullias, Paul E Sax, Naomi F Fields, Rochelle P Walensky, Emily P Hyle
Background: Current guidelines recommend genotype resistance testing at diagnosis to guide initial selection of antiretroviral therapy (ART). Many standard resistance genotypes exclude testing for resistance to integrase inhibitors ("IR-testing"), although this class of drugs is a component of most recommended first-line regimens. Methods: We compared the 96-week clinical outcomes and cost-effectiveness of two strategies: no IR-testing vs. IR-testing performed at HIV diagnosis...
June 9, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/28602075/a-synthetic-recombinase-based-feedback-loop-results-in-robust-expression
#16
Thomas Folliard, Harrison Steel, Thomas P Prescott, George Wadhams, Lynn J Rothschild, Antonis Papachristodoulou
Accurate control of a biological process is essential for many critical functions in biology, from the cell cycle to proteome regulation. To achieve this, negative feedback is frequently employed to provide a highly robust and reliable output. Feedback is found throughout biology and technology, but due to challenges posed by its implementation, it is yet to be widely adopted in synthetic biology. In this paper we design a synthetic feedback network using a class of recombinase proteins called integrases, which can be re-engineered to flip the orientation of DNA segments in a digital manner...
June 21, 2017: ACS Synthetic Biology
https://www.readbyqxmd.com/read/28599144/making-serine-integrases-work-for-us
#17
REVIEW
W Marshall Stark
DNA site-specific recombinases are enzymes (often associated with mobile DNA elements) that catalyse breaking and rejoining of DNA strands at specific points, thereby bringing about precise genetic rearrangements. Serine integrases are a group of recombinases derived from bacteriophages. Their unusual properties, including directionality of recombination and simple site requirements, are leading to their development as efficient, versatile tools for applications in experimental biology, biotechnology, synthetic biology and gene therapy...
June 6, 2017: Current Opinion in Microbiology
https://www.readbyqxmd.com/read/28598790/croi-2017-advances-in-antiretroviral-therapy
#18
Joyce Jones, Barbara S Taylor, Hong-Van Tieu, Timothy J Wilkin
The 2017 Conference on Retroviruses and Opportunistic Infections (CROI) featured exciting preclinical data on investigational antiretroviral agents with good in vitro efficacy and long half-lives. Investigational medications, including bictegravir, demonstrated excellent efficacy and tolerability, as did dual-agent therapy with dolutegravir paired with rilpivirine or with lamivudine. Dolutegravir monotherapy proved inadvisable due to virologic failure and resistance. The gap between high- and low-income settings along the HIV care continuum is narrowing, with Zimbabwe, Malawi, and Zambia approaching the 90-90-90 targets established by the joint United Nations Programme on HIV/AIDS (UNAIDS), whereas communities in the Southern United States are falling behind...
May 2017: Topics in Antiviral Medicine
https://www.readbyqxmd.com/read/28583191/hiv-drug-resistance-against-strand-transfer-integrase-inhibitors
#19
REVIEW
Kaitlin Anstett, Bluma Brenner, Thibault Mesplede, Mark A Wainberg
Integrase strand transfer inhibitors (INSTIs) are the newest class of antiretroviral drugs to be approved for treatment and act by inhibiting the essential HIV protein integrase from inserting the viral DNA genome into the host cell's chromatin. Three drugs of this class are currently approved for use in HIV-positive individuals: raltegravir (RAL), elvitegravir (EVG), and dolutegravir (DTG), while cabotegravir (CAB) and bictegravir (BIC) are currently in clinical trials. RAL and EVG have been successful in clinical settings but have relatively low genetic barriers to resistance...
June 5, 2017: Retrovirology
https://www.readbyqxmd.com/read/28582696/structural-basis-for-the-potent-inhibition-of-the-hiv-integrase-ledgf-p75-protein-protein-interaction
#20
Sergio R Ribone, Mario A Quevedo
Integrase (IN) constitutes one of the key enzymes involved in the lifecycle of the Human Immunodeficiency Virus (HIV), the etiological agent of AIDS. The biological role of IN strongly depends on the recognition and binding of cellular cofactors belonging to the infected host cell. Thus, the inhibition of the protein-protein interaction (PPI) between IN and cellular cofactors has been envisioned as a promising therapeutic target. In the present work we explore a structure-activity relationship for a set of 14 compounds reported as inhibitors of the PPI between IN and the lens epithelium-derived growth factor (LEDGF/p75)...
May 26, 2017: Journal of Molecular Graphics & Modelling
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