2a839193b3f42accea911ce11bd6b174 pmc_9951915.pdf dcb241b40f43441ce3c8fbac39c36973783f2d6c pmc_9951915.pdf f288c87acbe6089930917630d1181d20b1297f52e3d15b98a470c2fc235cec20 pmc_9951915.pdf Title: Systematic In Silico Assessment of Antimicrobial Resistance Dissemination across the Global Plasmidome Subject: The emergence of pathogenic strains resistant to multiple antimicrobials is a pressing problem in modern healthcare. Antimicrobial resistance is mediated primarily by dissemination of resistance determinants via horizontal gene transfer. The dissemination of some resistance genes has been well documented, but few studies have analyzed the patterns underpinning the dissemination of antimicrobial resistance genes. Analyzing the %GC content of plasmid-borne antimicrobial resistance genes relative to their host genome %GC content provides a means to efficiently detect and quantify dissemination of antimicrobial resistance genes. In this work we automate %GC content analysis to perform a comprehensive analysis of known antimicrobial resistance genes in publicly available plasmid sequences. We find that the degree to which antimicrobial resistance genes are disseminated depends primarily on the resistance mechanism. Our analysis identifies conjugative plasmids as primary dissemination vectors and indicates that most broadly disseminated genes have spread from single genomic backgrounds. We show that resistance dissemination profiles vary greatly among antimicrobials, oftentimes reflecting stewardship measures. Our findings establish %GC content analysis as a powerful, intuitive and scalable method to monitor the dissemination of resistance determinants using publicly available sequence data. Keywords: antimicrobial resistance; dissemination; evolution; plasmid; mobile genetic element; GC content; horizontal gene transfer Author: Miquel Sánchez-Osuna, Jordi Barbé and Ivan Erill Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Wed Feb 1 02:31:00 2023 CET ModDate: Wed Feb 1 03:04:16 2023 CET Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 18 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 71195189 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- MWHIBA+VnURWPalladioL Type 1 Custom yes yes no 10 0 AYEYNM+URWPalladioL-Bold Type 1 Custom yes yes no 15 0 TAMNKJ+URWPalladioL-Roma Type 1 Custom yes yes no 20 0 CIZAWT+URWPalladioL-Ital Type 1 Custom yes yes no 24 0 GIFXFT+VnURWPalladioL-Bold Type 1 Custom yes yes no 28 0 YYFPCJ+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 47 0 BCDEEE+PalatinoLinotype-Bold TrueType WinAnsi yes yes no 87 0 BCDFEE+PalatinoLinotype-Roman TrueType WinAnsi yes yes no 91 0 BCDGEE+PalatinoLinotype-Italic TrueType WinAnsi yes yes no 95 0 AINHDX+CMSY10 Type 1 Builtin yes yes no 103 0 LWLIVD+EURM10 Type 1 Builtin yes yes no 117 0 BCDEEE+PalatinoLinotype-Bold TrueType WinAnsi yes yes no 129 0 BCDFEE+PalatinoLinotype-Roman TrueType WinAnsi yes yes no 133 0 BCDGEE+PalatinoLinotype-Italic TrueType WinAnsi yes yes no 137 0 BCDIEE+PalatinoLinotype-Roman CID TrueType Identity-H yes yes yes 141 0 MPUDFL+PazoMath Type 1 Builtin yes yes no 155 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2023-12-15 02:34:51 CET RepresentationInformation: pmc_9951915.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2023-03-16 02:19:18 CET Size: 71195189 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 431 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Results and Discussion Destination: section.2 Children: Item: Title: Independent Mobilization and Dissemination of Antimicrobial Resistance Genes Destination: subsection.2.1 Item: Title: Resistance Mechanisms Determine the Prevalence of ARG Dissemination Destination: subsection.2.2 Item: Title: Antimicrobial Agent Classes Present Different Dissemination Patterns Destination: subsection.2.3 Item: Title: Conjugative Plasmids Mediate Dissemination of Antimicrobial Resistance Genes Destination: subsection.2.4 Item: Title: Materials and Methods Destination: section.3 Children: Item: Title: Antimicrobial Resistance Gene Prediction, Classification and Plasmid Analysis Destination: subsection.3.1 Item: Title: Antimicrobial Resistance Gene Dissemination Analysis Destination: subsection.3.2 Item: Title: Conclusions Destination: section.4 Item: Title: References Destination: section.4 Info: Title: Systematic In Silico Assessment of Antimicrobial Resistance Dissemination across the Global Plasmidome Author: Miquel Sánchez-Osuna, Jordi Barbé and Ivan Erill Subject: The emergence of pathogenic strains resistant to multiple antimicrobials is a pressing problem in modern healthcare. Antimicrobial resistance is mediated primarily by dissemination of resistance determinants via horizontal gene transfer. The dissemination of some resistance genes has been well documented, but few studies have analyzed the patterns underpinning the dissemination of antimicrobial resistance genes. Analyzing the %GC content of plasmid-borne antimicrobial resistance genes relative to their host genome %GC content provides a means to efficiently detect and quantify dissemination of antimicrobial resistance genes. In this work we automate %GC content analysis to perform a comprehensive analysis of known antimicrobial resistance genes in publicly available plasmid sequences. We find that the degree to which antimicrobial resistance genes are disseminated depends primarily on the resistance mechanism. Our analysis identifies conjugative plasmids as primary dissemination vectors and indicates that most broadly disseminated genes have spread from single genomic backgrounds. We show that resistance dissemination profiles vary greatly among antimicrobials, oftentimes reflecting stewardship measures. Our findings establish %GC content analysis as a powerful, intuitive and scalable method to monitor the dissemination of resistance determinants using publicly available sequence data. 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