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https://www.readbyqxmd.com/read/28730479/analysis-of-drug-resistance-using-kinome-wide-functional-screens
#1
Katherine R Singleton, Keith T Earley, Lynn E Heasley
The clinical success of tyrosine kinase inhibitors specific for BCR-ABL-, EGFR-, ALK-, and ROS1-driven cancers continues to spur the quest to match specific oncogene-defined tumor types with an appropriate molecularly targeted therapy. Unfortunately, responses to these agents are not durable with intrinsic or acquired resistance limiting benefit. Additionally, efforts to identify the appropriate targets of new drugs have focused on nonfunctional assays such as large-scale sequencing for somatic mutations or analysis of gene copy number...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28728166/whole-genome-sequencing-revealed-novel-prognostic-biomarkers-and-promising-targets-for-therapy-of-ovarian-clear-cell-carcinoma
#2
Hiroaki Itamochi, Tetsuro Oishi, Nao Oumi, Satoshi Takeuchi, Kosuke Yoshihara, Mikio Mikami, Nobuo Yaegashi, Yasuhisa Terao, Kazuhiro Takehara, Kimio Ushijima, Hidemichi Watari, Daisuke Aoki, Tadashi Kimura, Toshiaki Nakamura, Yoshihito Yokoyama, Junzo Kigawa, Toru Sugiyama
BACKGROUND: Ovarian clear cell carcinoma (OCCC) is mostly resistant to standard chemotherapy that results in poor patient survival. To understand the genetic background of these tumours, we performed whole-genome sequencing of OCCC tumours. METHODS: Tumour tissue samples and matched blood samples were obtained from 55 Japanese women diagnosed with OCCC. Whole-genome sequencing was performed using the Illumina HiSeq platform according to standard protocols. RESULTS: Alterations to the switch/sucrose non-fermentable (SWI/SNF) subunit, the phosphatidylinositol-3-kinase (PI3K)/Akt signalling pathway, and the receptor tyrosine kinase (RTK)/Ras signalling pathway were found in 51%, 42%, and 29% of OCCC tumours, respectively...
July 20, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28725045/genomic-epidemiology-of-global-klebsiella-pneumoniae-carbapenemase-kpc-producing-escherichia-coli
#3
N Stoesser, A E Sheppard, G Peirano, L W Anson, L Pankhurst, R Sebra, H T T Phan, A Kasarskis, A J Mathers, T E A Peto, P Bradford, M R Motyl, A S Walker, D W Crook, J D Pitout
The dissemination of carbapenem resistance in Escherichia coli has major implications for the management of common infections. bla KPC, encoding a transmissible carbapenemase (KPC), has historically largely been associated with Klebsiella pneumoniae, a predominant plasmid (pKpQIL), and a specific transposable element (Tn4401, ~10 kb). Here we characterize the genetic features of bla KPC emergence in global E. coli, 2008-2013, using both long- and short-read whole-genome sequencing. Amongst 43/45 successfully sequenced bla KPC-E...
July 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28724393/methicillin-resistant-staphylococcus-aureus-emerged-long-before-the-introduction-of-methicillin-into-clinical-practice
#4
Catriona P Harkins, Bruno Pichon, Michel Doumith, Julian Parkhill, Henrik Westh, Alexander Tomasz, Herminia de Lencastre, Stephen D Bentley, Angela M Kearns, Matthew T G Holden
BACKGROUND: The spread of drug-resistant bacterial pathogens poses a major threat to global health. It is widely recognised that the widespread use of antibiotics has generated selective pressures that have driven the emergence of resistant strains. Methicillin-resistant Staphylococcus aureus (MRSA) was first observed in 1960, less than one year after the introduction of this second generation beta-lactam antibiotic into clinical practice. Epidemiological evidence has always suggested that resistance arose around this period, when the mecA gene encoding methicillin resistance carried on an SCCmec element, was horizontally transferred to an intrinsically sensitive strain of S...
July 20, 2017: Genome Biology
https://www.readbyqxmd.com/read/28724084/comparison-of-models-and-whole-genome-profiling-approaches-for-genomic-enabled-prediction-of-septoria-tritici-blotch-stagonospora-nodorum-blotch-and-tan-spot-resistance-in-wheat
#5
Philomin Juliana, Ravi P Singh, Pawan K Singh, Jose Crossa, Jessica E Rutkoski, Jesse A Poland, Gary C Bergstrom, Mark E Sorrells
The leaf spotting diseases in wheat that include Septoria tritici blotch (STB) caused by , Stagonospora nodorum blotch (SNB) caused by , and tan spot (TS) caused by pose challenges to breeding programs in selecting for resistance. A promising approach that could enable selection prior to phenotyping is genomic selection that uses genome-wide markers to estimate breeding values (BVs) for quantitative traits. To evaluate this approach for seedling and/or adult plant resistance (APR) to STB, SNB, and TS, we compared the predictive ability of least-squares (LS) approach with genomic-enabled prediction models including genomic best linear unbiased predictor (GBLUP), Bayesian ridge regression (BRR), Bayes A (BA), Bayes B (BB), Bayes Cπ (BC), Bayesian least absolute shrinkage and selection operator (BL), and reproducing kernel Hilbert spaces markers (RKHS-M), a pedigree-based model (RKHS-P) and RKHS markers and pedigree (RKHS-MP)...
July 2017: Plant Genome
https://www.readbyqxmd.com/read/28724072/genome-wide-analysis-of-tar-spot-complex-resistance-in-maize-using-genotyping-by-sequencing-snps-and-whole-genome-prediction
#6
Shiliang Cao, Alexander Loladze, Yibing Yuan, Yongsheng Wu, Ao Zhang, Jiafa Chen, Gordon Huestis, Jingsheng Cao, Vijay Chaikam, Michael Olsen, Boddupalli M Prasanna, Felix San Vicente, Xuecai Zhang
Tar spot complex (TSC) is one of the most destructive foliar diseases of maize ( L.) in tropical and subtropical areas of Central and South America, causing significant grain yield losses when weather conditions are conducive. To dissect the genetic architecture of TSC resistance in maize, association mapping, in conjunction with linkage mapping, was conducted on an association-mapping panel and three biparental doubled-haploid (DH) populations using genotyping-by-sequencing (GBS) single-nucleotide polymorphisms (SNPs)...
July 2017: Plant Genome
https://www.readbyqxmd.com/read/28722566/molecular-epidemiology-of-staphylococcus-aureus-skin-and-soft-tissue-infections-in-the-lao-people-s-democratic-republic
#7
Alicia D Yeap, Kate Woods, David A B Dance, Bruno Pichon, Sayaphet Rattanavong, Viengmon Davong, Rattanaphone Phetsouvanh, Paul N Newton, Nandini Shetty, Angela M Kearns
This is the first report of the molecular epidemiology of Staphylococcus aureus from skin and soft tissue infections (SSTI) in Laos. We selected a random sample of 96 S. aureus SSTI isolates received by the Microbiology Laboratory, Mahosot Hospital, Vientiane, between July 2012 and June 2014, including representation from seven referral hospitals. Isolates underwent susceptibility testing by Clinical and Laboratory Standards Institute methods, spa typing and DNA microarray analysis, with whole genome sequencing for rare lineages...
May 30, 2017: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/28720731/an-in-vitro-chicken-gut-model-demonstrates-transfer-of-a-multidrug-resistance-plasmid-from-salmonella-to-commensal-escherichia-coli
#8
Roderick M Card, Shaun A Cawthraw, Javier Nunez-Garcia, Richard J Ellis, Gemma Kay, Mark J Pallen, Martin J Woodward, Muna F Anjum
The chicken gastrointestinal tract is richly populated by commensal bacteria that fulfill various beneficial roles for the host, including helping to resist colonization by pathogens. It can also facilitate the conjugative transfer of multidrug resistance (MDR) plasmids between commensal and pathogenic bacteria which is a significant public and animal health concern as it may affect our ability to treat bacterial infections. We used an in vitro chemostat system to approximate the chicken cecal microbiota, simulate colonization by an MDR Salmonella pathogen, and examine the dynamics of transfer of its MDR plasmid harboring several genes, including the extended-spectrum beta-lactamase blaCTX-M1 We also evaluated the impact of cefotaxime administration on plasmid transfer and microbial diversity...
July 18, 2017: MBio
https://www.readbyqxmd.com/read/28717172/evolution-of-the-pseudomonas-aeruginosa-mutational-resistome-in-an-international-cystic-fibrosis-clone
#9
Carla López-Causapé, Lea Mette Sommer, Gabriel Cabot, Rosa Rubio, Alain A Ocampo-Sosa, Helle Krogh Johansen, Joan Figuerola, Rafael Cantón, Timothy J Kidd, Soeren Molin, Antonio Oliver
Emergence of epidemic clones and antibiotic resistance development compromises the management of Pseudomonas aeruginosa cystic fibrosis (CF) chronic respiratory infections. Whole genome sequencing (WGS) was used to decipher the phylogeny, interpatient dissemination, WGS mutator genotypes (mutome) and resistome of a widespread clone (CC274), in isolates from two highly-distant countries, Australia and Spain, covering an 18-year period. The coexistence of two divergent CC274 clonal lineages was revealed, but without evident geographical barrier; phylogenetic reconstructions and mutational resistome demonstrated the interpatient transmission of mutators...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28716462/rapid-identification-of-a-mycobacterium-tuberculosis-full-genetic-drug-resistance-profile-through-whole-genome-sequencing-directly-from-sputum
#10
Camus Nimmo, Ronan Doyle, Carrie Burgess, Rachel Williams, Rebecca Gorton, Timothy D McHugh, Mike Brown, Stephen Morris-Jones, Helen Booth, Judith Breuer
INTRODUCTION: Resistance to second line tuberculosis drugs is common, but slow to diagnose with phenotypic drug sensitivity testing. Rapid molecular tests speed up diagnosis, but can only detect limited mutations. Whole genome sequencing (WGS) of culture isolates can generate a complete genetic drug resistance profile, but is delayed by the initial culture step. We previously successfully achieved WGS directly from sputum using targeted enrichment. CASE REPORT: A 29-year-old Nigerian lady was diagnosed with tuberculosis...
July 14, 2017: International Journal of Infectious Diseases: IJID
https://www.readbyqxmd.com/read/28716113/whole-metagenome-profiles-of-particulates-collected-from-the-international-space-station
#11
Nicholas A Be, Aram Avila-Herrera, Jonathan E Allen, Nitin Singh, Aleksandra Checinska Sielaff, Crystal Jaing, Kasthuri Venkateswaran
BACKGROUND: The built environment of the International Space Station (ISS) is a highly specialized space in terms of both physical characteristics and habitation requirements. It is unique with respect to conditions of microgravity, exposure to space radiation, and increased carbon dioxide concentrations. Additionally, astronauts inhabit a large proportion of this environment. The microbial composition of ISS particulates has been reported; however, its functional genomics, which are pertinent due to potential impact of its constituents on human health and operational mission success, are not yet characterized...
July 17, 2017: Microbiome
https://www.readbyqxmd.com/read/28713356/a-genotypic-analysis-of-five-p-aeruginosa-strains-after-biofilm-infection-by-phages-targeting-different-cell-surface-receptors
#12
Diana P Pires, Andreas Dötsch, Erin M Anderson, Youai Hao, Cezar M Khursigara, Joseph S Lam, Sanna Sillankorva, Joana Azeredo
Antibiotic resistance constitutes one of the most serious threats to the global public health and urgently requires new and effective solutions. Bacteriophages are bacterial viruses increasingly recognized as being good alternatives to traditional antibiotic therapies. In this study, the efficacy of phages, targeting different cell receptors, against Pseudomonas aeruginosa PAO1 biofilm and planktonic cell cultures was evaluated over the course of 48 h. Although significant reductions in the number of viable cells were achieved for both cases, the high level of adaptability of the bacteria in response to the selective pressure caused by phage treatment resulted in the emergence of phage-resistant variants...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28712319/primary-liver-cancer-genome-sequencing-translational-implications-and-challenges
#13
Demosthenes E Ziogas, Ioannis D Kyrochristos, Georgios K Glantzounis, Dimitrios Christodoulou, Evangelos Felekouras, Dimitrios H Roukos
The prognosis of primary liver cancer (PLC) remains poor and is explained by the slow progress in understanding the molecular pathways driving tumorigenesis, therapeutic resistance and relapse. For early PLCs, complete surgical resection is the only effective treatment, with sorafenib and, more recently, regorafenib prolonging overall survival by a few months. Areas covered: Application of next-generation sequencing (NGS), including targeted NGS (tNGS), whole-exome sequencing (WES), whole-genome sequencing (WGS) and RNA sequencing (RNAseq), on clinical samples from patients with hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) could aid in comprehending tumorigenesis, genetic and genomic heterogeneity, as well as developing molecular classifications for specialized targeted therapy...
July 17, 2017: Expert Review of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28711585/global-outbreak-of-severe-mycobacterium-chimaera-disease-after-cardiac-surgery-a-molecular-epidemiological-study
#14
Jakko van Ingen, Thomas A Kohl, Katharina Kranzer, Barbara Hasse, Peter M Keller, Anna Katarzyna Szafrańska, Doris Hillemann, Meera Chand, Peter Werner Schreiber, Rami Sommerstein, Christoph Berger, Michele Genoni, Christian Rüegg, Nicolas Troillet, Andreas F Widmer, Sören L Becker, Mathias Herrmann, Tim Eckmanns, Sebastian Haller, Christiane Höller, Sylvia B Debast, Maurice J Wolfhagen, Joost Hopman, Jan Kluytmans, Merel Langelaar, Daan W Notermans, Jaap Ten Oever, Peter van den Barselaar, Alexander B A Vonk, Margreet C Vos, Nada Ahmed, Timothy Brown, Derrick Crook, Theresa Lamagni, Nick Phin, E Grace Smith, Maria Zambon, Annerose Serr, Tim Götting, Winfried Ebner, Alexander Thürmer, Christian Utpatel, Cathrin Spröer, Boyke Bunk, Ulrich Nübel, Guido V Bloemberg, Erik C Böttger, Stefan Niemann, Dirk Wagner, Hugo Sax
BACKGROUND: Since 2013, over 100 cases of Mycobacterium chimaera prosthetic valve endocarditis and disseminated disease were notified in Europe and the USA, linked to contaminated heater-cooler units (HCUs) used during cardiac surgery. We did a molecular epidemiological investigation to establish the source of these patients' disease. METHODS: We included 24 M chimaera isolates from 21 cardiac surgery-related patients in Switzerland, Germany, the Netherlands, and the UK, 218 M chimaera isolates from various types of HCUs in hospitals, from LivaNova (formerly Sorin; London, UK) and Maquet (Rastatt, Germany) brand HCU production sites, and unrelated environmental sources and patients, as well as eight Mycobacterium intracellulare isolates...
July 12, 2017: Lancet Infectious Diseases
https://www.readbyqxmd.com/read/28711508/virulent-and-pathogenic-features-on-the-cronobacter-sakazakii-polymyxin-resistant-pmr-mutant-strain-s-3
#15
Xuerui Bao, Ling Yang, Lequn Chen, Bing Li, Lin Li, Yanyan Li, Zhenbo Xu
Cronobacter sakazakii is a well-known opportunistic pathogen responsible for necrotizing enterocolitis, meningitis and septicaemia in the premature, immunocompromised infants and neonates. This pathogen possesses various virulence factors and regulatory systems, and pmrA/pmrB regulatory system has been identified in a variety of bacterial species. The current study aims to investigate role of pmrA gene in the pathogenicity and virulence characteristics of Cronobacter sakazakii using whole genome sequencing and RNA-seq...
July 12, 2017: Microbial Pathogenesis
https://www.readbyqxmd.com/read/28711439/updates-on-k13-mutant-alleles-for-artemisinin-resistance-in-plasmodium-falciparum
#16
REVIEW
Myo Thura Zaw, Nor Amalina Emran, Zaw Lin
BACKGROUND: In the fight against malaria caused by Plasmodium falciparum, the successes achieved by artemisinin were endangered by resistance of the parasites to the drug. Whole genome sequencing approach on artemisinin resistant parasite line discovered k13 gene associated with drug resistance. In vitro and in vivo studies indicated mutations in the k13 gene were linked to the artemisinin resistance. METHODOLOGY: The literatures published after April, 2015 up to December, 2016 on k13 mutant alleles for artemisinin resistance in Plasmodium falciparum and relevant literatures were comprehensively reviewed...
June 29, 2017: Journal of Microbiology, Immunology, and Infection, Wei Mian Yu Gan Ran za Zhi
https://www.readbyqxmd.com/read/28711389/population-genetic-structure-antibiotic-resistance-capsule-switching-and-evolution-of-invasive-pneumococci-before-conjugate-vaccination-in-malawi
#17
Chrispin Chaguza, Jennifer E Cornick, Cheryl P Andam, Rebecca A Gladstone, Maaike Alaerts, Patrick Musicha, Chikondi Peno, Naor Bar-Zeev, Arox W Kamng'ona, Anmol M Kiran, Chisomo L Msefula, Lesley McGee, Robert F Breiman, Aras Kadioglu, Neil French, Robert S Heyderman, William P Hanage, Stephen D Bentley, Dean B Everett
INTRODUCTION: Pneumococcal infections cause a high death toll in Sub Saharan Africa (SSA) but the recently rolled out pneumococcal conjugate vaccines (PCV) will reduce the disease burden. To better understand the population impact of these vaccines, comprehensive analysis of large collections of pneumococcal isolates sampled prior to vaccination is required. Here we present a population genomic study of the invasive pneumococcal isolates sampled before the implementation of PCV13 in Malawi...
July 12, 2017: Vaccine
https://www.readbyqxmd.com/read/28711315/characterization-of-mobile-genetic-elements-carrying-vim-1-and-kpc-2-carbapenemases-in-citrobacter-freundii-isolates-in-madrid
#18
Jennifer Villa, David M Arana, Esther Viedma, Dafne Perez-Montarelo, Fernando Chaves
Carbapenemase producing Citrobacter freundii (CPCF) infections are still uncommon in European countries. Here we report a molecular study conducted in a tertiary care facility in southern Madrid, Spain, from 2009 to 2014 to investigate the epidemiology of CPCF. The blaIMP-1,blaIMP-2,blaKPC,blaNDM,blaOXA-48,blaVIM-1 and blaVIM-2 genes were screened by PCR. Molecular typing was carried out by Pulsed-field gel electrophoresis analysis (PFGE) and multilocus sequence typing (MLST). Whole genome sequencing (WGS) was performed to characterize the resistome and the mobile genetic elements associated with the carbapenems resistance of CPCF...
July 8, 2017: International Journal of Medical Microbiology: IJMM
https://www.readbyqxmd.com/read/28708586/whole-genome-and-transcriptome-analysis-reveal-maldi-tof-ms-and-sds-page-have-limited-performance-for-the-detection-of-the-key-outer-membrane-protein-in-carbapenem-resistant-klebsiella-pneumoniae-isolates
#19
Naina Adren Pinto, Roshan D'Souza, In Sik Hwang, Jongrak Choi, Yong Ha In, Hyung Soon Park, Choong-Min Ryu, Dongeun Yong, Kyungwon Lee
To detect the outer membrane protein (OMP), which plays a key role in carbapenem resistance, whole-genome and transcriptome analysis of the clinical carbapenem-resistant Klebsiella pneumoniae was carried out. The index strain lacked both OmpK35 and OmpK36, whereas the other strains lacked only OmpK35. After SDS-PAGE, the putative OMP bands were excised and identified as OmpA and OmpK36. MALDI-TOF MS showed peaks at ~36 and ~38 kDa that corresponded to OmpA and OmpK36, respectively. In all the strains except YMC2014/03/P345, the ~38 kDa peaks were present...
July 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28706242/draft-whole-genome-sequence-of-groundnut-stem-rot-fungus-athelia-rolfsii-revealing-genetic-architect-of-its-pathogenicity-and-virulence
#20
M A Iquebal, Rukam S Tomar, M V Parakhia, Deepak Singla, Sarika Jaiswal, V M Rathod, S M Padhiyar, Neeraj Kumar, Anil Rai, Dinesh Kumar
Groundnut (Arachis hypogaea L.) is an important oil seed crop having major biotic constraint in production due to stem rot disease caused by fungus, Athelia rolfsii causing 25-80% loss in productivity. As chemical and biological combating strategies of this fungus are not very effective, thus genome sequencing can reveal virulence and pathogenicity related genes for better understanding of the host-parasite interaction. We report draft assembly of Athelia rolfsii genome of ~73 Mb having 8919 contigs. Annotation analysis revealed 16830 genes which are involved in fungicide resistance, virulence and pathogenicity along with putative effector and lethal genes...
July 13, 2017: Scientific Reports
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