Mode and dynamics of vanA-type vancomycin resistance dissemination in Dutch hospitals
Abstract Background Enterococcus faecium is a commensal of the gastrointestinal tract of animals and humans but also a causative agent of hospital-acquired infections. Resistance against glycopeptides and to vancomycin has motivated the inclusion of E. faecium in the WHO global priority list. Vancom...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2021-01-01
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| Series: | Genome Medicine |
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| Online Access: | https://doi.org/10.1186/s13073-020-00825-3 |
| _version_ | 1818722229109653504 |
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| author | Sergio Arredondo-Alonso Janetta Top Jukka Corander Rob J. L. Willems Anita C. Schürch |
| author_facet | Sergio Arredondo-Alonso Janetta Top Jukka Corander Rob J. L. Willems Anita C. Schürch |
| author_sort | Sergio Arredondo-Alonso |
| collection | DOAJ |
| description | Abstract Background Enterococcus faecium is a commensal of the gastrointestinal tract of animals and humans but also a causative agent of hospital-acquired infections. Resistance against glycopeptides and to vancomycin has motivated the inclusion of E. faecium in the WHO global priority list. Vancomycin resistance can be conferred by the vanA gene cluster on the transposon Tn1546, which is frequently present in plasmids. The vanA gene cluster can be disseminated clonally but also horizontally either by plasmid dissemination or by Tn1546 transposition between different genomic locations. Methods We performed a retrospective study of the genomic epidemiology of 309 vancomycin-resistant E. faecium (VRE) isolates across 32 Dutch hospitals (2012–2015). Genomic information regarding clonality and Tn1546 characterization was extracted using hierBAPS sequence clusters (SC) and TETyper, respectively. Plasmids were predicted using gplas in combination with a network approach based on shared k-mer content. Next, we conducted a pairwise comparison between isolates sharing a potential epidemiological link to elucidate whether clonal, plasmid, or Tn1546 spread accounted for vanA-type resistance dissemination. Results On average, we estimated that 59% of VRE cases with a potential epidemiological link were unrelated which was defined as VRE pairs with a distinct Tn1546 variant. Clonal dissemination accounted for 32% cases in which the same SC and Tn1546 variants were identified. Horizontal plasmid dissemination accounted for 7% of VRE cases, in which we observed VRE pairs belonging to a distinct SC but carrying an identical plasmid and Tn1546 variant. In 2% of cases, we observed the same Tn1546 variant in distinct SC and plasmid types which could be explained by mixed and consecutive events of clonal and plasmid dissemination. Conclusions In related VRE cases, the dissemination of the vanA gene cluster in Dutch hospitals between 2012 and 2015 was dominated by clonal spread. However, we also identified outbreak settings with high frequencies of plasmid dissemination in which the spread of resistance was mainly driven by horizontal gene transfer (HGT). This study demonstrates the feasibility of distinguishing between modes of dissemination with short-read data and provides a novel assessment to estimate the relative contribution of nested genomic elements in the dissemination of vanA-type resistance. |
| first_indexed | 2024-12-17T20:51:18Z |
| format | Article |
| id | doaj.art-612295f6e726406685eab31ac1c3307e |
| institution | Directory Open Access Journal |
| issn | 1756-994X |
| language | English |
| last_indexed | 2024-12-17T20:51:18Z |
| publishDate | 2021-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Genome Medicine |
| spelling | doaj.art-612295f6e726406685eab31ac1c3307e2022-12-21T21:33:01ZengBMCGenome Medicine1756-994X2021-01-0113111810.1186/s13073-020-00825-3Mode and dynamics of vanA-type vancomycin resistance dissemination in Dutch hospitalsSergio Arredondo-Alonso0Janetta Top1Jukka Corander2Rob J. L. Willems3Anita C. Schürch4Department of Medical Microbiology, University Medical Center UtrechtDepartment of Medical Microbiology, University Medical Center UtrechtDepartment of Biostatistics, University of OsloDepartment of Medical Microbiology, University Medical Center UtrechtDepartment of Medical Microbiology, University Medical Center UtrechtAbstract Background Enterococcus faecium is a commensal of the gastrointestinal tract of animals and humans but also a causative agent of hospital-acquired infections. Resistance against glycopeptides and to vancomycin has motivated the inclusion of E. faecium in the WHO global priority list. Vancomycin resistance can be conferred by the vanA gene cluster on the transposon Tn1546, which is frequently present in plasmids. The vanA gene cluster can be disseminated clonally but also horizontally either by plasmid dissemination or by Tn1546 transposition between different genomic locations. Methods We performed a retrospective study of the genomic epidemiology of 309 vancomycin-resistant E. faecium (VRE) isolates across 32 Dutch hospitals (2012–2015). Genomic information regarding clonality and Tn1546 characterization was extracted using hierBAPS sequence clusters (SC) and TETyper, respectively. Plasmids were predicted using gplas in combination with a network approach based on shared k-mer content. Next, we conducted a pairwise comparison between isolates sharing a potential epidemiological link to elucidate whether clonal, plasmid, or Tn1546 spread accounted for vanA-type resistance dissemination. Results On average, we estimated that 59% of VRE cases with a potential epidemiological link were unrelated which was defined as VRE pairs with a distinct Tn1546 variant. Clonal dissemination accounted for 32% cases in which the same SC and Tn1546 variants were identified. Horizontal plasmid dissemination accounted for 7% of VRE cases, in which we observed VRE pairs belonging to a distinct SC but carrying an identical plasmid and Tn1546 variant. In 2% of cases, we observed the same Tn1546 variant in distinct SC and plasmid types which could be explained by mixed and consecutive events of clonal and plasmid dissemination. Conclusions In related VRE cases, the dissemination of the vanA gene cluster in Dutch hospitals between 2012 and 2015 was dominated by clonal spread. However, we also identified outbreak settings with high frequencies of plasmid dissemination in which the spread of resistance was mainly driven by horizontal gene transfer (HGT). This study demonstrates the feasibility of distinguishing between modes of dissemination with short-read data and provides a novel assessment to estimate the relative contribution of nested genomic elements in the dissemination of vanA-type resistance.https://doi.org/10.1186/s13073-020-00825-3Enterococcus faeciumGenome sequencingVancomycin resistanceNetworkClonal disseminationHorizontal dissemination |
| spellingShingle | Sergio Arredondo-Alonso Janetta Top Jukka Corander Rob J. L. Willems Anita C. Schürch Mode and dynamics of vanA-type vancomycin resistance dissemination in Dutch hospitals Genome Medicine Enterococcus faecium Genome sequencing Vancomycin resistance Network Clonal dissemination Horizontal dissemination |
| title | Mode and dynamics of vanA-type vancomycin resistance dissemination in Dutch hospitals |
| title_full | Mode and dynamics of vanA-type vancomycin resistance dissemination in Dutch hospitals |
| title_fullStr | Mode and dynamics of vanA-type vancomycin resistance dissemination in Dutch hospitals |
| title_full_unstemmed | Mode and dynamics of vanA-type vancomycin resistance dissemination in Dutch hospitals |
| title_short | Mode and dynamics of vanA-type vancomycin resistance dissemination in Dutch hospitals |
| title_sort | mode and dynamics of vana type vancomycin resistance dissemination in dutch hospitals |
| topic | Enterococcus faecium Genome sequencing Vancomycin resistance Network Clonal dissemination Horizontal dissemination |
| url | https://doi.org/10.1186/s13073-020-00825-3 |
| work_keys_str_mv | AT sergioarredondoalonso modeanddynamicsofvanatypevancomycinresistancedisseminationindutchhospitals AT janettatop modeanddynamicsofvanatypevancomycinresistancedisseminationindutchhospitals AT jukkacorander modeanddynamicsofvanatypevancomycinresistancedisseminationindutchhospitals AT robjlwillems modeanddynamicsofvanatypevancomycinresistancedisseminationindutchhospitals AT anitacschurch modeanddynamicsofvanatypevancomycinresistancedisseminationindutchhospitals |