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- Title
Fitness cost of vancomycin-resistant Enterococcus faecium plasmids associated with hospital infection outbreaks.
- Authors
Tedim, Ana P; Lanza, Val F; Rodríguez, Concepción M; Freitas, Ana R; Novais, Carla; Peixe, Luísa; Baquero, Fernando; Coque, Teresa M
- Abstract
<bold>Background: </bold>Vancomycin resistance is mostly associated with Enterococcus faecium due to Tn1546-vanA located on narrow- and broad-host plasmids of various families. This study's aim was to analyse the effects of acquiring Tn1546-carrying plasmids with proven epidemicity in different bacterial host backgrounds.<bold>Methods: </bold>Widespread Tn1546-carrying plasmids of different families RepA_N (n = 5), Inc18 (n = 4) and/or pHTβ (n = 1), and prototype plasmids RepA_N (pRUM) and Inc18 (pRE25, pIP501) were analysed. Plasmid transferability and fitness cost were assessed using E. faecium (GE1, 64/3) and Enterococcus faecalis (JH2-2/FA202/UV202) recipient strains. Growth curves (Bioscreen C) and Relative Growth Rates were obtained in the presence/absence of vancomycin. Plasmid stability was analysed (300 generations). WGS (Illumina-MiSeq) of non-evolved and evolved strains (GE1/64/3 transconjugants, n = 49) was performed. SNP calling (Breseq software) of non-evolved strains was used for comparison.<bold>Results: </bold>All plasmids were successfully transferred to different E. faecium clonal backgrounds. Most Tn1546-carrying plasmids and Inc18 and RepA_N prototypes reduced host fitness (-2% to 18%) while the cost of Tn1546 expression varied according to the Tn1546-variant and the recipient strain (9%-49%). Stability of Tn1546-carrying plasmids was documented in all cases, often with loss of phenotypic resistance and/or partial plasmid deletions. SNPs and/or indels associated with essential bacterial functions were observed on the chromosome of evolved strains, some of them linked to increased fitness.<bold>Conclusions: </bold>The stability of E. faecium Tn1546-carrying plasmids in the absence of selective pressure and the high intra-species conjugation rates might explain the persistence of vancomycin resistance in E. faecium populations despite the significant burden they might impose on bacterial host strains.
- Subjects
ENTEROCOCCAL infections; ENTEROCOCCUS faecium; PLASMIDS; VANCOMYCIN resistance; ENTEROCOCCUS faecalis; PHENOTYPES; CHROMOSOMES; BACTERIAL proteins; RESEARCH; DNA; RESEARCH methodology; CROSS infection; VANCOMYCIN; MEDICAL cooperation; EVALUATION research; GRAM-positive bacterial infections; COMPARATIVE studies; GENES; EPIDEMICS; PHARMACODYNAMICS
- Publication
Journal of Antimicrobial Chemotherapy (JAC), 2021, Vol 76, Issue 11, p2757
- ISSN
0305-7453
- Publication type
journal article
- DOI
10.1093/jac/dkab249