Reactive Infection Control Strategy for Control of New Delhi Metallo-β-Lactamase (NDM)-Producing Enterobacteriaceae Analyzed Using Whole-Genome Sequencing: Hits and Misses

2016 ◽  
Vol 37 (8) ◽  
pp. 987-990 ◽  
Author(s):  
Kalisvar Marimuthu ◽  
Oon Tek Ng ◽  
Wei Xin Khong ◽  
Eryu Xia ◽  
Yik-Ying Teo ◽  
...  
Keyword(s):  
Phylogenetic Analysis ◽  
Infection Control ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Control Strategy ◽  
Infect Control Hosp ◽  
The Other ◽  
New Delhi ◽  
Whole Genome ◽  
Direct Transmission

Genetically distinct isolates of New Delhi metallo-β-lactamase (NDM)–producing Enterobacteriaceae were identified from the clinical cultures of 6 patients. Screening of shared-ward contacts identified 2 additional NDM-positive patients. Phylogenetic analysis proved that 1 contact was a direct transmission while the other was unrelated to the index, suggesting hidden routes of transmission.Infect Control Hosp Epidemiol 2016;37:987–990

Whole Genome Sequencing and Phylogenetic Analysis of the Rabies Virus Strain Moscow 3253 Adapted to a Vero Cell Line

2020 ◽  
Vol 35 (4) ◽  
pp. 237-242
Author(s):  
Ya. M. Krasnov ◽  
Zh. V. Alkhova ◽  
S. V. Generalov ◽  
I. V. Tuchkov ◽  
E. A. Naryshkina ◽  
...  
Keyword(s):  
Phylogenetic Analysis ◽  
Vero Cell ◽  
Whole Genome Sequencing ◽  
Cell Line ◽  
Rabies Virus ◽  
Genome Sequencing ◽  
Virus Strain ◽  
Whole Genome ◽  
Vero Cell Line ◽  
Rabies Virus Strain

Identification of multiple species and subpopulations among Australian clinical Sporothrix isolates using whole genome sequencing

2018 ◽  
Vol 57 (7) ◽  
pp. 905-908 ◽  
Author(s):  
David New ◽  
Alicia G Beukers ◽  
Sarah E Kidd ◽  
Adam J Merritt ◽  
Kerry Weeks ◽  
...  
Keyword(s):  
Phylogenetic Analysis ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Sporothrix Schenckii ◽  
Sensu Stricto ◽  
Northern Territory ◽  
Whole Genome ◽  
Phylogenetic Resolution ◽  
Genetic Clustering ◽  
Multiple Species

AbstractWhole genome sequencing (WGS) was used to demonstrate the wide genetic variability within Sporothrix schenckii sensu lato and establish that there are two main species of Sporothrix within Australian clinical isolates—S. schenckii sensu stricto and Sporothrix globosa. We also demonstrated southwest Western Australia contained genetically similar S. schenckii ss strains that are distinct from strains isolated in the eastern and northern states of Australia. Some genetic clustering by region was also noted for northern NSW, Queensland, and Northern Territory. Phylogenetic analysis of WGS data provided greater phylogenetic resolution compared to analysis of the calmodulin gene alone.

scholarly journals Putative Integrative Mobile Elements That Exploit the Xer Recombination Machinery Carrying blaIMI-Type Carbapenemase Genes in Enterobacter cloacae Complex Isolates in Singapore

2017 ◽  
Vol 62 (1) ◽  
Author(s):  
Tse H. Koh ◽  
Nurdyana Binte Abdul Rahman ◽  
Jeanette W. P. Teo ◽  
My-Van La ◽  
Balamurugan Periaswamy ◽  
...  
Keyword(s):  
Phylogenetic Analysis ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Multilocus Sequence Typing ◽  
Enterobacter Cloacae ◽  
Mobile Elements ◽  
Whole Genome ◽  
Content Type ◽  
Flanking Regions ◽  
Enterobacter Cloacae Complex

ABSTRACT Whole-genome sequencing was performed on 16 isolates of the carbapenemase-producing Enterobacter cloacae complex to determine the flanking regions of bla IMI-type genes. Phylogenetic analysis of multilocus sequence typing (MLST) targets separated the isolates into 4 clusters. The bla IMI-type genes were all found on Xer-dependent integrative mobile elements (IMEX). The IMEX elements of 5 isolates were similar to those described in Canada, while the remainder were novel. Five isolates had IMEX elements lacking a resolvase and recombinase.

scholarly journals Candidate Predisposition Variants in Kaposi Sarcoma as Detected by Whole-Genome Sequencing

2019 ◽  
Vol 6 (10) ◽  
Author(s):  
Sanni J Rinne ◽  
Lauri J Sipilä ◽  
Päivi Sulo ◽  
Emmanuelle Jouanguy ◽  
Vivien Béziat ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Kaposi Sarcoma ◽  
The Other ◽  
Whole Genome ◽  
Genome Wide ◽  
Starting Point ◽  
Familial Clustering ◽  
Iranian Family ◽  
Classic Kaposi Sarcoma

Abstract Familial clustering of classic Kaposi sarcoma (CKS) is rare with, approximately 100 families reported to date. We studied 2 consanguineous families, 1 Iranian and 1 Israeli, with multiple cases of adult CKS and without overt underlying immunodeficiency. We performed genome-wide linkage analysis and whole-genome sequencing to discover the putative genetic cause for predisposition. A 9-kb homozygous intronic deletion in RP11-259O2.1 in the Iranian family and 2 homozygous variants, 1 in SCUBE2 and the other in CDHR5, in the Israeli family were identified as possible candidates. The presented variants provide a robust starting point for validation in independent samples.

scholarly journals 531. Practical and Evidence-Based Considerations for Implementation of Bacterial Whole-Genome Sequencing Within Longitudinal Infection Control Practice

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S255-S255
Author(s):  
Donald S Chen ◽  
Moira Quinn ◽  
Rita M Sussner ◽  
Guiqing Wang ◽  
John T Fallon ◽  
...  
Keyword(s):  
Infection Control ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Tertiary Care ◽  
False Negative ◽  
Lessons Learned ◽  
Evidence Based ◽  
Guidance Document ◽  
Whole Genome ◽  
Care Hospital

Abstract Background Whole-genome sequencing (WGS) of bacteria is becoming a routine tool within microbiology, yet its utility to help guide infection control (IC) practice longitudinally is underexplored. As with any technology adopted in the hospital, the integration of WGS into IC practice must be carefully managed and considered. We qualitatively report an evidence-based implementation workflow that considers WGS to help proactively guide IC professionals during investigation of infectious outbreaks. Methods We built upon lessons learned in an ongoing surveillance effort at a tertiary care hospital—utilizing retrospective WGS data within the Philips IntelliSpace Epidemiology system—to understand facilitators and barriers to the use of bacterial WGS longitudinally to inform IC workflow. Our team established a 9-month workgroup to study the practical aspects of implementing WGS in routine IC practice. From expert opinion collected via the workgroup, in addition to evidence from the literature, a workflow guidance document and checklist were codified. New ideas included incorporating education to promote the establishment of an IC triage process. Results Facilitators to implementation included ability to display genomic relatedness alongside relevant patient data to enable clinical actionability, ability to pivot time and resources rapidly when infections are a pseudo outbreak (false positive) or missed outbreak (false negative), opportunities for nuanced staff education, and willingness to be a first-of-kind adopter. Barriers were communication of genomic concepts to IC professionals and relevant institutional stakeholders, maintaining sharable notes of active investigations to promote data-sharing practices, and timing and review of relevant interventions into the facility workflow. Strategies to address these issues are considered. Conclusion This study provides a novel framework for adaptation of existing IC workflow strategies to leverage the utility of bacterial WGS, and it presents a schema to effectively engage relevant stakeholders, based on an analysis of the unique challenges inherent within IC practice. It also offers an innovative model for the development and implementation of IC workflows to account for, and adapt to, site-specific conditions. Disclosures All authors: No reported disclosures.

DNA Sequencing of a Murine Acute Promyelocytic Leukemia (APL) Genome Using Next Generation Technology.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3965-3965
Author(s):  
Lukas D. Wartman ◽  
Li Ding ◽  
David E. Larson ◽  
Michael D. McLellan ◽  
Heather Schmidt ◽  
...  
Keyword(s):  
Mouse Model ◽  
Dna Sequencing ◽  
Whole Genome Sequencing ◽  
Acute Promyelocytic Leukemia ◽  
Genome Sequencing ◽  
Somatic Mutations ◽  
Promyelocytic Leukemia ◽  
The Other ◽  
Whole Genome ◽  
Base Pairs

Abstract Abstract 3965 Poster Board III-901 We have recently established that whole genome sequencing is a valid, unbiased approach that can identify novel candidate mutations that may be important for AML pathogenesis (Ley et al Nature 2008, Mardis et al NEJM 2009). Acute promyelocytic leukemia (APL, FAB M3 AML) is a subtype of AML characterized by the t(15;17)(q22;q11.2) translocation that creates an oncogenic fusion gene, PML-RARA. Our laboratory has previously modeled APL in a mouse in an effort to understand the genetic events that lead to the disease. In our knockin mouse model, a human PML-RARA cDNA was targeted to the 5' untranslated region of the mouse cathepsin G gene on chromosome 14 (mCG-PR). The targeting vector was transfected into the RW-4 embryonic stem cell line, derived from a 129/SvJ mouse. The transfected RW-4 cells were injected into C57Bl/6 blastocysts, and chimeric offspring were bred to C57Bl/6 mice. F1 129/SvJ x C57Bl/6 mice were subsequently backcrossed onto the B6/Taconic background for 10 generations before establishing a tumor watch. About 60% of the mCG-PR mice in the Bl/6 background develop a disease that closely resembles APL only after a latent period of 7-18 months, suggesting that additional progression mutations are required for APL development. Array-based genomic techniques (expression array studies and high resolution CGH) have revealed some recurring genetic alterations that may be relevant for progression (i.e. an interstitial deletion of chromosome 2, trisomy 15, etc.), but gene-specific progression mutations have not yet been identified. To begin to identify these mutations in an unbiased fashion, we sequenced a cytogenetically normal, diploid mouse APL genome using massively parallel DNA sequencing via the Illumina platform. Since the tumor arose in a highly inbred mouse strain, we predicted that 15x coverage of the genome (approximately 40 billion base pairs of sequence) would be necessary to identify >90% of the heterozygous somatic mutations. We generated 2 Illumina paired-end libraries (insert sizes of 300-350 bp and 550-600 bp) and generated 59.64 billion base pairs of sequence with 3 full sequencing runs; the reads that successfully mapped generated 15.6x coverage. The sequence data predicted 87,778 heterozygous Single Nucleotide Variants (SNVs) compared to the mouse C57Bl6/J reference sequence, and 23,439 homozygous SNVs. Of the predicted heterozygous SNVs, 695 were non-synonymous (missense or nonsense, or altering a canonical splice site). Thus far, 80 of these putative non-synonymous SNVs have been further analyzed using Sanger sequencing of the original tumor DNA vs. pooled B6/Taconic spleen DNA and pooled129/SvJ spleen DNA as controls. 37/80 were shown to be false positive calls, and 37 were inherited SNPs from residual regions of the129/SvJ genome. 6/80 were present only in the tumor genome, and were candidate somatic mutations. These 6 were screened in 89 additional murine APL tumor samples derived from the same mouse model. Mutations in the Jarid2 (L915I) and Capns2 (N149S) genes occurred only in the proband, and are therefore of uncertain significance. 4/6 mutations were found in additional samples; 3 of these mutations were derived from a common ancestor of the proband and the other affected mice, and were therefore not relevant for pathogenesis. The other recurring mutation was in the pseudokinase domain of JAK1 (V657F), and was identified in one other mouse that was not closely related to the proband. This mutation is orthologous to the known activating mutation V617F in human JAK2, and is identical to a recently described JAK1 pseudokinase domain mutation (V658F) found in human APL and T-ALL samples (EG Jeong et al, Clin Can Res 14: 3716, 2008). We are currently testing the functional significance of this mutation by expressing it in bone marrow cells derived from young WT vs. mCG-PR mice. In summary, unbiased whole genome sequencing of a mouse APL genome has identified a recurring mutation of JAK1 found in both human and mouse APL samples. This approach may allow us to rapidly identify progression mutations that are common to human and murine AML, and provides an important proof-of-concept that this mouse model of AML is functionally related to its human counterpart. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Integration of Whole-Genome Sequencing into Infection Control Practices: the Potential and the Hurdles

2015 ◽  
Vol 53 (4) ◽  
pp. 1054-1055 ◽  
Author(s):  
Elizabeth Robilotti ◽  
Mini Kamboj
Keyword(s):  
Infection Control ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Clinical Epidemiology ◽  
Great Promise ◽  
Whole Genome ◽  
Related Article ◽  
Link Type ◽  
Article Type ◽  
Transmission Pathways

Microbial whole-genome sequencing (WGS) is poised to transform many of the currently used approaches in medical microbiology. Recent reports on the application of WGS to understand genetic evolution and reconstruct transmission pathways have provided valuable information that will influence infection control practices. While this technology holds great promise, obstacles to full implementation remain. Two articles in this issue of the Journal of Clinical Microbiology (S. Octavia, Q. Wang, M. M. Tanaka, S. Kaur, V. Sintchenko, and R. Lan, J Clin Microbiol 53:1063–1071, 2015, doi:10.1128/JCM.03235-14, andS. J. Salipante, D. J. SenGupta, L. A. Cummings, T. A. Land, D. R. Hoogestraat, and B. T. Cookson, J Clin Microbiol 53:1072–1079, 2015, doi:10.1128/JCM.03385-14) describe the breadth of application of WGS to the field of clinical epidemiology.

Sign in / Sign up

Export Citation Format

Share Document