Inter-species geographic signatures for tracing horizontal gene transfer and long-term persistence of carbapenem resistance
Abstract Background Carbapenem-resistant Enterobacterales (CRE) are an urgent global health threat. Inferring the dynamics of local CRE dissemination is currently limited by our inability to confidently trace the spread of resistance determinants to unrelated bacterial hosts. Whole-genome sequence c...
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| Format: | Article |
| Language: | English |
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BMC
2022-04-01
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| Series: | Genome Medicine |
| Online Access: | https://doi.org/10.1186/s13073-022-01040-y |
| _version_ | 1811272622446477312 |
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| author | Rauf Salamzade Abigail L. Manson Bruce J. Walker Thea Brennan-Krohn Colin J. Worby Peijun Ma Lorrie L. He Terrance P. Shea James Qu Sinéad B. Chapman Whitney Howe Sarah K. Young Jenna I. Wurster Mary L. Delaney Sanjat Kanjilal Andrew B. Onderdonk Cassiana E. Bittencourt Gabrielle M. Gussin Diane Kim Ellena M. Peterson Mary Jane Ferraro David C. Hooper Erica S. Shenoy Christina A. Cuomo Lisa A. Cosimi Susan S. Huang James E. Kirby Virginia M. Pierce Roby P. Bhattacharyya Ashlee M. Earl |
| author_facet | Rauf Salamzade Abigail L. Manson Bruce J. Walker Thea Brennan-Krohn Colin J. Worby Peijun Ma Lorrie L. He Terrance P. Shea James Qu Sinéad B. Chapman Whitney Howe Sarah K. Young Jenna I. Wurster Mary L. Delaney Sanjat Kanjilal Andrew B. Onderdonk Cassiana E. Bittencourt Gabrielle M. Gussin Diane Kim Ellena M. Peterson Mary Jane Ferraro David C. Hooper Erica S. Shenoy Christina A. Cuomo Lisa A. Cosimi Susan S. Huang James E. Kirby Virginia M. Pierce Roby P. Bhattacharyya Ashlee M. Earl |
| author_sort | Rauf Salamzade |
| collection | DOAJ |
| description | Abstract Background Carbapenem-resistant Enterobacterales (CRE) are an urgent global health threat. Inferring the dynamics of local CRE dissemination is currently limited by our inability to confidently trace the spread of resistance determinants to unrelated bacterial hosts. Whole-genome sequence comparison is useful for identifying CRE clonal transmission and outbreaks, but high-frequency horizontal gene transfer (HGT) of carbapenem resistance genes and subsequent genome rearrangement complicate tracing the local persistence and mobilization of these genes across organisms. Methods To overcome this limitation, we developed a new approach to identify recent HGT of large, near-identical plasmid segments across species boundaries, which also allowed us to overcome technical challenges with genome assembly. We applied this to complete and near-complete genome assemblies to examine the local spread of CRE in a systematic, prospective collection of all CRE, as well as time- and species-matched carbapenem-susceptible Enterobacterales, isolated from patients from four US hospitals over nearly 5 years. Results Our CRE collection comprised a diverse range of species, lineages, and carbapenem resistance mechanisms, many of which were encoded on a variety of promiscuous plasmid types. We found and quantified rearrangement, persistence, and repeated transfer of plasmid segments, including those harboring carbapenemases, between organisms over multiple years. Some plasmid segments were found to be strongly associated with specific locales, thus representing geographic signatures that make it possible to trace recent and localized HGT events. Functional analysis of these signatures revealed genes commonly found in plasmids of nosocomial pathogens, such as functions required for plasmid retention and spread, as well survival against a variety of antibiotic and antiseptics common to the hospital environment. Conclusions Collectively, the framework we developed provides a clearer, high-resolution picture of the epidemiology of antibiotic resistance importation, spread, and persistence in patients and healthcare networks. |
| first_indexed | 2024-04-12T22:43:40Z |
| format | Article |
| id | doaj.art-57dc460746d040e3850323d8b6411193 |
| institution | Directory Open Access Journal |
| issn | 1756-994X |
| language | English |
| last_indexed | 2024-04-12T22:43:40Z |
| publishDate | 2022-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Genome Medicine |
| spelling | doaj.art-57dc460746d040e3850323d8b64111932022-12-22T03:13:38ZengBMCGenome Medicine1756-994X2022-04-0114112210.1186/s13073-022-01040-yInter-species geographic signatures for tracing horizontal gene transfer and long-term persistence of carbapenem resistanceRauf Salamzade0Abigail L. Manson1Bruce J. Walker2Thea Brennan-Krohn3Colin J. Worby4Peijun Ma5Lorrie L. He6Terrance P. Shea7James Qu8Sinéad B. Chapman9Whitney Howe10Sarah K. Young11Jenna I. Wurster12Mary L. Delaney13Sanjat Kanjilal14Andrew B. Onderdonk15Cassiana E. Bittencourt16Gabrielle M. Gussin17Diane Kim18Ellena M. Peterson19Mary Jane Ferraro20David C. Hooper21Erica S. Shenoy22Christina A. Cuomo23Lisa A. Cosimi24Susan S. Huang25James E. Kirby26Virginia M. Pierce27Roby P. Bhattacharyya28Ashlee M. Earl29Infectious Disease and Microbiome Program, Broad Institute of MIT and HarvardInfectious Disease and Microbiome Program, Broad Institute of MIT and HarvardInfectious Disease and Microbiome Program, Broad Institute of MIT and HarvardDepartment of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical SchoolInfectious Disease and Microbiome Program, Broad Institute of MIT and HarvardInfectious Disease and Microbiome Program, Broad Institute of MIT and HarvardInfectious Disease and Microbiome Program, Broad Institute of MIT and HarvardInfectious Disease and Microbiome Program, Broad Institute of MIT and HarvardInfectious Disease and Microbiome Program, Broad Institute of MIT and HarvardInfectious Disease and Microbiome Program, Broad Institute of MIT and HarvardInfectious Disease and Microbiome Program, Broad Institute of MIT and HarvardInfectious Disease and Microbiome Program, Broad Institute of MIT and HarvardDepartment of Ophthalmology, Department of Microbiology, Harvard Medical School and Massachusetts Eye and Ear InfirmaryDivision of Infectious Disease, Brigham and Women’s Hospital, Harvard Medical SchoolDivision of Infectious Disease, Brigham and Women’s Hospital, Harvard Medical SchoolDivision of Infectious Disease, Brigham and Women’s Hospital, Harvard Medical SchoolDepartment of Pathology and Laboratory Medicine, University of California Irvine School of MedicineDivision of Infectious Diseases, University of California Irvine School of MedicineDivision of Infectious Diseases, University of California Irvine School of MedicineDepartment of Pathology and Laboratory Medicine, University of California Irvine School of MedicineMassachusetts General HospitalMassachusetts General HospitalMassachusetts General HospitalInfectious Disease and Microbiome Program, Broad Institute of MIT and HarvardInfectious Disease and Microbiome Program, Broad Institute of MIT and HarvardDivision of Infectious Diseases, University of California Irvine School of MedicineDepartment of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical SchoolMassachusetts General HospitalInfectious Disease and Microbiome Program, Broad Institute of MIT and HarvardInfectious Disease and Microbiome Program, Broad Institute of MIT and HarvardAbstract Background Carbapenem-resistant Enterobacterales (CRE) are an urgent global health threat. Inferring the dynamics of local CRE dissemination is currently limited by our inability to confidently trace the spread of resistance determinants to unrelated bacterial hosts. Whole-genome sequence comparison is useful for identifying CRE clonal transmission and outbreaks, but high-frequency horizontal gene transfer (HGT) of carbapenem resistance genes and subsequent genome rearrangement complicate tracing the local persistence and mobilization of these genes across organisms. Methods To overcome this limitation, we developed a new approach to identify recent HGT of large, near-identical plasmid segments across species boundaries, which also allowed us to overcome technical challenges with genome assembly. We applied this to complete and near-complete genome assemblies to examine the local spread of CRE in a systematic, prospective collection of all CRE, as well as time- and species-matched carbapenem-susceptible Enterobacterales, isolated from patients from four US hospitals over nearly 5 years. Results Our CRE collection comprised a diverse range of species, lineages, and carbapenem resistance mechanisms, many of which were encoded on a variety of promiscuous plasmid types. We found and quantified rearrangement, persistence, and repeated transfer of plasmid segments, including those harboring carbapenemases, between organisms over multiple years. Some plasmid segments were found to be strongly associated with specific locales, thus representing geographic signatures that make it possible to trace recent and localized HGT events. Functional analysis of these signatures revealed genes commonly found in plasmids of nosocomial pathogens, such as functions required for plasmid retention and spread, as well survival against a variety of antibiotic and antiseptics common to the hospital environment. Conclusions Collectively, the framework we developed provides a clearer, high-resolution picture of the epidemiology of antibiotic resistance importation, spread, and persistence in patients and healthcare networks.https://doi.org/10.1186/s13073-022-01040-y |
| spellingShingle | Rauf Salamzade Abigail L. Manson Bruce J. Walker Thea Brennan-Krohn Colin J. Worby Peijun Ma Lorrie L. He Terrance P. Shea James Qu Sinéad B. Chapman Whitney Howe Sarah K. Young Jenna I. Wurster Mary L. Delaney Sanjat Kanjilal Andrew B. Onderdonk Cassiana E. Bittencourt Gabrielle M. Gussin Diane Kim Ellena M. Peterson Mary Jane Ferraro David C. Hooper Erica S. Shenoy Christina A. Cuomo Lisa A. Cosimi Susan S. Huang James E. Kirby Virginia M. Pierce Roby P. Bhattacharyya Ashlee M. Earl Inter-species geographic signatures for tracing horizontal gene transfer and long-term persistence of carbapenem resistance Genome Medicine |
| title | Inter-species geographic signatures for tracing horizontal gene transfer and long-term persistence of carbapenem resistance |
| title_full | Inter-species geographic signatures for tracing horizontal gene transfer and long-term persistence of carbapenem resistance |
| title_fullStr | Inter-species geographic signatures for tracing horizontal gene transfer and long-term persistence of carbapenem resistance |
| title_full_unstemmed | Inter-species geographic signatures for tracing horizontal gene transfer and long-term persistence of carbapenem resistance |
| title_short | Inter-species geographic signatures for tracing horizontal gene transfer and long-term persistence of carbapenem resistance |
| title_sort | inter species geographic signatures for tracing horizontal gene transfer and long term persistence of carbapenem resistance |
| url | https://doi.org/10.1186/s13073-022-01040-y |
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