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  • 1
    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 6, No. Supplement_2 ( 2019-10-23), p. S263-S264
    Abstract: The MRSA Chilean-Cordobes (ChC) clone belongs to the clonal complex 5 (CC5) and typically carries SCCmec I. The ChC clone predominated widely throughout several countries of Latin America (LA), but during the mid-2000s a CA-MRSA CC8 LA variant (USA300-LV) quickly replaced the ChC in Colombia and Ecuador. Most notably, this replacement was not observed in Peru or Chile. Here, we aimed to understand the phylogenomic relatedness of the CC5 ChC clone obtained from different countries of LA. Methods We sequenced and analyzed the genomes of 115 MRSA isolates obtained between 2011–2014 from bloodstream infections in 6 LA countries (Argentina, Brazil, Colombia, Chile, Peru, and Venezuela). All isolates were confirmed as ChC clone by pulsed-field gel electrophoresis (PFGE). We used core genome-based phylogenomic reconstructions and molecular clock analysis to infer the relationships and time of divergence between clades. Results Whole-genome-based multilocus sequence typing determined that 110/115 isolates belonged to ST5 and carried SCCmec I. The phylogenomic reconstruction showed ChC isolates clustered into 4 major clades distinctly segregated by country of origin (Figure 1). Interestingly, isolates recovered from Chile divided into 2 different clades that segregate according to the city of origin (Santiago [SCL] or Concepción [CON] ), suggesting these clades evolved independently. Molecular clock analyses suggested all clades share a common ancestor with the divergence of the Chilean clades occurring earlier (Figure 2). Of note, analysis of heavy metal genes suggested the divergence between Chilean isolates was characterized by the loss of a mercury resistance gene cluster, which is present in an 88% of CON isolates, but only in 28% of SCL (Figure 2). Conclusion MRSA isolates belonging to the ChC clone from 6 LA countries clustered in 4 clades according to the geographical region of isolation. This segregation suggests divergent adaptations that may respond to different selective pressures. Heavy metal resistance could play a role in the ability of the MRSA ChC to disseminate in specific geographical locations. Disclosures All authors: No reported disclosures.
    Type of Medium: Online Resource
    ISSN: 2328-8957
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2019
    detail.hit.zdb_id: 2757767-3
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  • 2
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 2020
    In:  Open Forum Infectious Diseases Vol. 7, No. Supplement_1 ( 2020-12-31), p. S299-S299
    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 7, No. Supplement_1 ( 2020-12-31), p. S299-S299
    Abstract: As the pandemic SARS-CoV-2 virus has spread globally its genome has diversified and distinct clones can now be recognized, tracked, and traced. Identifying clonal groups allows for assessment of geographic spread, transmission events, and identification of more virulent or transmissible emerging strains. Methods All SARS-CoV-2 genomes (n=17,504) that are complete and high coverage were downloaded from GISAID on May 17th 2020. We developed a GNU-based Virus IDentification (GNUVID) tool that implements a whole genome multilocus sequence typing (wgMLST) scheme composed of all ten ORFs in the SARS-CoV-2 genome. The 10,422 genomes that passed our quality check were fed to the GNUVID tool, which assigned a ST profile to each genome. Global optimum eBURST was then used to cluster the STs in clonal complexes (CCs). Results Our ST/CC analysis uncovered strong associations of ST/CCs with certain geographical regions but also dynamic local changes in ST/CC prevalence. We also identified several unexpected putative global transmission events (e.g., from the US to the Middle East and reintroduction to China later in the pandemic). We have made our tool (GNUVID) available so that new WG sequences can be rapidly assigned to an ST/CC (https://github.com/ahmedmagds/GNUVID). Conclusion Our sequence typing system uncovered previously unappreciated transmission events and waves of expansion and replacement of SARS-CoV-2 STs and CCs in different geographical locations, suggesting complex dynamics in viral populations that previously seemed monomorphic. Because, our tool can be rapidly updated with new sequencing data it can track emerging clones and identifying new hotspots. Disclosures All Authors: No reported disclosures
    Type of Medium: Online Resource
    ISSN: 2328-8957
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
    detail.hit.zdb_id: 2757767-3
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  • 3
    In: eLife, eLife Sciences Publications, Ltd, Vol. 10 ( 2021-07-19)
    Abstract: Carboxy ester prodrugs are widely employed to increase oral absorption and potency of phosphonate antibiotics. Prodrugging can mask problematic chemical features that prevent cellular uptake and may enable tissue-specific compound delivery. However, many carboxy ester promoieties are rapidly hydrolyzed by serum esterases, limiting their therapeutic potential. While carboxy ester-based prodrug targeting is feasible, it has seen limited use in microbes as microbial esterase-specific promoieties have not been described. Here we identify the bacterial esterases, GloB and FrmB, that activate carboxy ester prodrugs in Staphylococcus aureus. Additionally, we determine the substrate specificities for FrmB and GloB and demonstrate the structural basis of these preferences. Finally, we establish the carboxy ester substrate specificities of human and mouse sera, ultimately identifying several promoieties likely to be serum esterase-resistant and microbially labile. These studies will enable structure-guided design of antistaphylococcal promoieties and expand the range of molecules to target staphylococcal pathogens.
    Type of Medium: Online Resource
    ISSN: 2050-084X
    Language: English
    Publisher: eLife Sciences Publications, Ltd
    Publication Date: 2021
    detail.hit.zdb_id: 2687154-3
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  • 4
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 2021
    In:  Journal of the Pediatric Infectious Diseases Society Vol. 10, No. Supplement_4 ( 2021-12-24), p. S96-S105
    In: Journal of the Pediatric Infectious Diseases Society, Oxford University Press (OUP), Vol. 10, No. Supplement_4 ( 2021-12-24), p. S96-S105
    Abstract: The field of molecular epidemiology responded to the SARS-CoV-2 pandemic with an unrivaled amount of whole viral genome sequencing. By the time this sentence is published we will have well surpassed 1.5 million whole genomes, more than 4 times the number of all microbial whole genomes deposited in GenBank and 35 times the total number of viral genomes. This extraordinary dataset that accrued in near real time has also given us an opportunity to chart the global and local evolution of a virus as it moves through the world population. The data itself presents challenges that have never been dealt with in molecular epidemiology, and tracking a virus that is changing so rapidly means that we are often running to catch up. Here we review what is known about the evolution of the virus, and the critical impact that whole genomes have had on our ability to trace back and track forward the spread of lineages of SARS-CoV-2. We then review what whole genomes have told us about basic biological properties of the virus such as transmissibility, virulence, and immune escape with a special emphasis on pediatric disease. We couch this discussion within the framework of systematic biology and phylogenetics, disciplines that have proven their worth again and again for identifying and deciphering the spread of epidemics, though they were largely developed in areas far removed from infectious disease and medicine.
    Type of Medium: Online Resource
    ISSN: 2048-7207
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 2668791-4
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  • 5
    Online Resource
    Online Resource
    Elsevier BV ; 2020
    In:  Current Opinion in Microbiology Vol. 53 ( 2020-02), p. 61-70
    In: Current Opinion in Microbiology, Elsevier BV, Vol. 53 ( 2020-02), p. 61-70
    Type of Medium: Online Resource
    ISSN: 1369-5274
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2020
    detail.hit.zdb_id: 2019222-8
    SSG: 12
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  • 6
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 2021
    In:  Genome Biology and Evolution Vol. 13, No. 9 ( 2021-09-01)
    In: Genome Biology and Evolution, Oxford University Press (OUP), Vol. 13, No. 9 ( 2021-09-01)
    Abstract: Discrete classification of SARS-CoV-2 viral genotypes can identify emerging strains and detect geographic spread, viral diversity, and transmission events. We developed a tool (GNU-based Virus IDentification [GNUVID]) that integrates whole-genome multilocus sequence typing and a supervised machine learning random forest-based classifier. We used GNUVID to assign sequence type (ST) profiles to all high-quality genomes available from GISAID. STs were clustered into clonal complexes (CCs) and then used to train a machine learning classifier. We used this tool to detect potential introduction and exportation events and to estimate effective viral diversity across locations and over time in 16 US states. GNUVID is a highly scalable tool for viral genotype classification (https://github.com/ahmedmagds/GNUVID) that can quickly classify hundreds of thousands of genomes in a way that is consistent with phylogeny. Our genotyping ST/CC analysis uncovered dynamic local changes in ST/CC prevalence and diversity with multiple replacement events in different states, an average of 20.6 putative introductions and 7.5 exportations for each state over the time period analyzed. We introduce the use of effective diversity metrics (Hill numbers) that can be used to estimate the impact of interventions (e.g., travel restrictions, vaccine uptake, mask mandates) on the variation in circulating viruses. Our classification tool uncovered multiple introduction and exportation events, as well as waves of expansion and replacement of SARS-CoV-2 genotypes in different states. GNUVID classification lends itself to measures of ecological diversity, and, with systematic genomic sampling, it could be used to track circulating viral diversity and identify emerging clones and hotspots.
    Type of Medium: Online Resource
    ISSN: 1759-6653
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 2495328-3
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  • 7
    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 8, No. 7 ( 2021-07-01)
    Abstract: We report the genome of a B.1.1.7+E484K severe acute respiratory syndrome coronavirus 2 from Southeastern Pennsylvania and compare it with all high-coverage B.1.1.7+E484K genomes (n = 235) available. Analyses showed the existence of at least 4 distinct clades of this variant circulating in the United States and the possibility of at least 59 independent acquisitions of the E484K mutation.
    Type of Medium: Online Resource
    ISSN: 2328-8957
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 2757767-3
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  • 8
    In: eLife, eLife Sciences Publications, Ltd, Vol. 10 ( 2021-11-25)
    Type of Medium: Online Resource
    ISSN: 2050-084X
    Language: English
    Publisher: eLife Sciences Publications, Ltd
    Publication Date: 2021
    detail.hit.zdb_id: 2687154-3
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