scholarly journals Fitness cost of vancomycin-resistant Enterococcus faecium plasmids associated with hospital infection outbreaks

2021 ◽  
Author(s):  
Ana P Tedim ◽  
Val F Lanza ◽  
Concepción M Rodríguez ◽  
Ana R Freitas ◽  
Carla Novais ◽  
...  
Keyword(s):  
Enterococcus Faecium ◽  
Plasmid Stability ◽  
Growth Curves ◽  
Illumina Miseq ◽  
Vancomycin Resistance ◽  
Fitness Cost ◽  
Bacterial Host ◽  
Relative Growth Rates ◽  
Phenotypic Resistance ◽  
The Stability

Abstract Background 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. Methods 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. Results 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. Conclusions 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.

scholarly journals Fitness cost of vancomycin-resistant Enterococcus faecium plasmids associated with hospital infection outbreaks

2021 ◽  
Author(s):  
Ana P. Tedim ◽  
Val F. Lanza ◽  
Concepción M. Rodríguez ◽  
Ana R. Freitas ◽  
Carla Novais ◽  
...  
Keyword(s):  
Enterococcus Faecium ◽  
Plasmid Stability ◽  
Point Mutations ◽  
Growth Curves ◽  
Illumina Miseq ◽  
Vancomycin Resistance ◽  
Fitness Cost ◽  
Bacterial Host ◽  
Relative Growth Rates ◽  
Phenotypic Resistance

ABSTRACTBackgroundVancomycin resistance is mostly associated with Enterococcus faecium due to Tn1546-vanA located on narrow- and broad-host plasmids of various families. The study’s aim was to analyse the effects of acquiring Tn1546-plasmids with proven epidemicity in different bacterial host backgrounds.MethodsWidespread Tn1546-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 presence/absence of vancomycin. Plasmid stability was analysed (300 generations). Whole genome sequencing (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.ResultsAll plasmids were successfully transferred to different E. faecium clonal backgrounds. Most Tn1546-plasmids and Inc18 and RepA_N prototypes reduced host fitness (−2%-18%) while the cost of Tn1546 expression varied according to the Tn1546-variant and the recipient strain (9-49%). Stability of Tn1546-plasmids was documented in all cases, often with loss of phenotypic resistance and/or partial plasmid deletions. Point mutations and/or indels associated with essential bacterial functions were observed on the chromosome of evolved strains, some of them linked to increased fitness.ConclusionsThe stability of E. faecium Tn1546-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.

scholarly journals Attributable mortality of vancomycin resistance in ampicillin-resistant Enterococcus faecium bacteremia in Denmark and the Netherlands: A matched cohort study

2021 ◽  
pp. 1-9
Author(s):  
Wouter C. Rottier ◽  
Mette Pinholt ◽  
Akke K. van der Bij ◽  
Magnus Arpi ◽  
Sybrandus N. Blank ◽  
...  
Keyword(s):  
Cohort Study ◽  
The Netherlands ◽  
Antibiotic Therapy ◽  
Enterococcus Faecium ◽  
Mortality Rates ◽  
Vancomycin Resistance ◽  
Attributable Mortality ◽  
Matched Cohort ◽  
Matched Cohort Study ◽  
The Impact

Abstract Objective: To study whether replacement of nosocomial ampicillin-resistant Enterococcus faecium (ARE) clones by vancomycin-resistant E. faecium (VRE), belonging to the same genetic lineages, increases mortality in patients with E. faecium bacteremia, and to evaluate whether any such increase is mediated by a delay in appropriate antibiotic therapy. Design: Retrospective, matched-cohort study. Setting: The study included 20 Dutch and Danish hospitals from 2009 to 2014. Patients: Within the study period, 63 patients with VRE bacteremia (36 Dutch and 27 Danish) were identified and subsequently matched to 234 patients with ARE bacteremia (130 Dutch and 104 Danish) for hospital, ward, length of hospital stay prior to bacteremia, and age. For all patients, 30-day mortality after bacteremia onset was assessed. Methods: The risk ratio (RR) reflecting the impact of vancomycin resistance on 30-day mortality was estimated using Cox regression with further analytic control for confounding factors. Results: The 30-day mortality rates were 27% and 38% for ARE in the Netherlands and Denmark, respectively, and the 30-day mortality rates were 33% and 48% for VRE in these respective countries. The adjusted RR for 30-day mortality for VRE was 1.54 (95% confidence interval, 1.06–2.25). Although appropriate antibiotic therapy was initiated later for VRE than for ARE bacteremia, further analysis did not reveal mediation of the increased mortality risk. Conclusions: Compared to ARE bacteremia, VRE bacteremia was associated with higher 30-day mortality. One explanation for this association would be increased virulence of VRE, although both phenotypes belong to the same well-characterized core genomic lineage. Alternatively, it may be the result of unmeasured confounding.

Identical twins and developmental stability

1962 ◽  
Vol 4 (1) ◽  
pp. 144-164 ◽  
Author(s):  
C. S. Taylor
Keyword(s):  
Growth Curves ◽  
Identical Twins ◽  
Body Measurements ◽  
Frequency Distributions ◽  
Stability Of Development ◽  
Mean Size ◽  
Degree Of Maturity ◽  
The Stability ◽  
Average Size ◽  
Slow Growing

1. The stability with which dairy cattle develop in body size up to 2 years of age was studied in 60 pairs of uniformly treated identical twins, i.e. an assessment was made of the influence of season, genotype, mean size of twin pair, age and degree of maturity on the level of within-pair variability.2. The frequency distributions of size differences shown by one-egg twins were in many cases decidedly leptokurtic.3. The similarity in size of the identical twins studied was only slightly, if at all, influenced by season. Within-pair variability under free outdoor grazing was certainly not any greater than under semi-controlled conditions indoors.4. The stability with which cattle grew appeared to depend on their genotype. Identical twins of the Shorthorn breed were somewhat more alike in size than were the twins of other breed-types; crossbreds were, on average, 50 % less stable than purebreds in average size () ; although crossbreds grew with somewhat greater stability ().5. Whatever their mean size, all pairs of identical twins of the same breed appeared to grow postnatally with more or less equal stability (). Small, slow growing pairs showed a greater disparity in average size ().6. Stability of development continually changed with age but not violently. Each body measurement appeared to have its own characteristic age trend. It is false to believe that variation automatically increases with increasing age. As they grew older, identical twins tended to become less alike in their later maturing body measurements whereas their early maturing body measurements tended to decline in variability. There was an overall trend with degree of maturity; variability steadily increased to a maximum and subsequently declined.7. It is suggested that environmentally induced instability of development may remain at a minimum level so long as growth curves are not seriously distorted from their exponential path to maturity.

scholarly journals Synergism between β-Lactams and Glycopeptides against VanA-Type Methicillin-Resistant Staphylococcus aureus and Heterologous Expression of the vanA Operon

2006 ◽  
Vol 50 (11) ◽  
pp. 3622-3630 ◽  
Author(s):  
Bruno Périchon ◽  
Patrice Courvalin
Keyword(s):  
Staphylococcus Aureus ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Inhibitory Concentration ◽  
Vancomycin Resistance ◽  
Glycopeptide Resistance ◽  
Methicillin Resistant ◽  
Antagonistic Effects ◽  
Resistance Induction ◽  
The Stability ◽  
Time Kill

ABSTRACT Vancomycin resistance of Staphylococcus aureus NY-VRSA and VRSA-5 is due to acquisition of a vanA operon located in a Tn1546-like element. The vanA gene cluster of NY-VRSA contained one copy of insertion sequences IS1251 and IS1216V relative to that of VRSA-5. As evidenced by the nature of the late peptidoglycan precursors and by quantification of d,d-peptidase activities, the vancomycin resistance genes were efficiently expressed in both strains. Study of the stability and inducibility of glycopeptide resistance suggested that low-level glycopeptide resistance of NY-VRSA was most probably due to plasmid instability combined with a long delay for resistance induction. The activity of combinations of vancomycin or teicoplanin with oxacillin against the four VanA-type S. aureus strains already reported was tested by single and double disk diffusion, E-test on agar alone or supplemented with antibiotics, the checkerboard technique, and by determining time-kill curves. A strong synergism against the four clinical isolates, with fractional inhibitory concentration indexes from 0.008 to 0.024, was reproducibly observed between the two antibiotics by all methods. These observations indicate that cell wall inhibitors of the β-lactam and glycopeptide classes exert strong and mutual antagonistic effects on resistance to each other against VanA-type methicillin-resistant S. aureus.

scholarly journals A Sequence That Affects the Copy Number and Stability of pSW200 and ColE1

2010 ◽  
Vol 192 (14) ◽  
pp. 3654-3660 ◽  
Author(s):  
Ying-Chung Wu ◽  
Shih-Tung Liu
Keyword(s):  
Copy Number ◽  
Plasmid Stability ◽  
Efficient Synthesis ◽  
Transcriptional Fusion ◽  
Similar Sequence ◽  
Pantoea Stewartii ◽  
The Stability

ABSTRACT Pantoea stewartii SW2 contains 13 plasmids. One of these plasmids, pSW200, has a replicon that resembles that of ColE1. This study demonstrates that pSW200 contains a 9-bp UP element, 5′-AAGATCTTC, which is located immediately upstream of the −35 box in the RNAII promoter. A transcriptional fusion study reveals that substituting this 9-bp sequence reduces the activity of the RNAII promoter by 78%. The same mutation also reduced the number of plasmid copies from 13 to 5, as well as the plasmid stability. When a similar sequence in a ColE1 derivative, pYCW301, is mutated, the copy number of the plasmid also declines from 34 to 16 per cell. Additionally, inserting this 9-bp sequence stabilizes an unstable pSW100 derivative, pSW142K, which also contains a replicon resembling that of ColE1, indicating the importance of this sequence in maintaining the stability of the plasmid. In conclusion, the 9-bp sequence upstream of the −35 box in the RNAII promoter is required for the efficient synthesis of RNAII and maintenance of the stability of the plasmids in the ColE1 family.

scholarly journals Draft Genome Sequence of a Vancomycin-Resistant and Vancomycin-Dependent Enterococcus faecium Isolate

2016 ◽  
Vol 4 (2) ◽  
Author(s):  
Marion Blaschitz ◽  
Sarah Lepuschitz ◽  
Laura Wagner ◽  
Franz Allerberger ◽  
Alexander Indra ◽  
...  
Keyword(s):  
Genome Sequence ◽  
Enterococcus Faecium ◽  
Prolonged Exposure ◽  
Draft Genome ◽  
Vancomycin Resistance ◽  
Draft Genome Sequence ◽  
Nosocomial Pathogens ◽  
Vancomycin Resistant Enterococci ◽  
Vancomycin Resistant ◽  
Faecium Isolate

Vancomycin-resistant enterococci have emerged as major nosocomial pathogens worldwide. While antimicrobial pressure promotes nosocomial colonization with these enterococci, prolonged exposure to vancomycin may foster the transition from vancomycin resistance to vancomycin dependence. Here, we report the draft genome sequence of a vancomycin-dependent Enterococcus faecium isolate showing partial teicoplanin dependence.

scholarly journals Enterococcus faecium growth model

2009 ◽  
Vol 27 (No. 5) ◽  
pp. 361-371 ◽  
Author(s):  
P. Čermák ◽  
A. Landfeld ◽  
P. Měřička ◽  
M. Houška
Keyword(s):  
Experimental Data ◽  
Human Milk ◽  
Water Activity ◽  
Enterococcus Faecium ◽  
Growth Curves ◽  
Activity Level ◽  
Cow Milk ◽  
Activity Levels ◽  
Control Mechanisms ◽  
Ph Values

Enterococci are bacteria commonly found in humans. However, these bacteria can cause severe infections in susceptible individuals. The strains of <i>Enterococcus faecium</i> have demonstrated an increasing resistance to antibiotics, which is considered an important virulence factor. The contribution of <i>E. faecium</i> to the infection-related illnesses has recently increased, which involves most of the isolated Vancomycin-Resistant Enterococcus (VRE) strains. Enterococci are common contaminants of human milk processed in milk banks, and the consumption of contaminated milk can cause severe infection-related complications if the control mechanisms fail to detect the contamination. Extensive data are available on the growth curves of <i>E. faecium</i> in broth at pH values between 6 and 7, at temperatures of 5°C to 20°C, and for water activity values <i>a</i><sub>w</sub> of 0.97 to 0.997. These growth curves were replaced with non-linear Gompertz curves for microorganism growth, the parameters of which were correlated with the temperature and pH values. A mathematical relationship to water activity could not be established since only two water activity levels have been experimentally tested and the resulting model would be highly inaccurate. The issue of water activity was resolved by the development of two separate models, one for each of the water activity values. The models correspond very well with the experimental growth curve data from which they were developed. The model for the water activity level of 0.997 was used to predict the growth of <i>E. faecium</i> in cow and human milks (these two fluids have practically identical water activity), and the prediction was compared to the experimental data. A good agreement between the predicted and experimental data was achieved for cow milk. With human milk, the model usually predicted a more rapid growth rate than that seen experimentally. The model was thus on the conservative side in all cases. The inhibitory agents naturally present in human milk might be responsible for the slower growth rates.

scholarly journals Persistence of Transferable Extended-Spectrum-β-Lactamase Resistance in the Absence of Antibiotic Pressure

2012 ◽  
Vol 56 (9) ◽  
pp. 4703-4706 ◽  
Author(s):  
Jennifer L. Cottell ◽  
Mark A. Webber ◽  
Laura J. V. Piddock
Keyword(s):  
Antibiotic Resistance ◽  
Resistance Gene ◽  
Resistance Genes ◽  
Antibiotic Resistance Genes ◽  
Fitness Cost ◽  
Resistant Bacteria ◽  
Bacterial Host ◽  
Antibiotic Resistant ◽  
M 14 ◽  
Host Strains

ABSTRACTThe treatment of infections caused by antibiotic-resistant bacteria is one of the great challenges faced by clinicians in the 21st century. Antibiotic resistance genes are often transferred between bacteria by mobile genetic vectors called plasmids. It is commonly believed that removal of antibiotic pressure will reduce the numbers of antibiotic-resistant bacteria due to the perception that carriage of resistance imposes a fitness cost on the bacterium. This study investigated the ability of the plasmid pCT, a globally distributed plasmid that carries an extended-spectrum-β-lactamase (ESBL) resistance gene (blaCTX-M-14), to persist and disseminate in the absence of antibiotic pressure. We investigated key attributes in plasmid success, including conjugation frequencies, bacterial-host growth rates, ability to cause infection, and impact on the fitness of host strains. We also determined the contribution of theblaCTX-M-14gene itself to the biology of the plasmid and host bacterium. Carriage of pCT was found to impose no detectable fitness cost on various bacterial hosts. An absence of antibiotic pressure and inactivation of the antibiotic resistance gene also had no effect on plasmid persistence, conjugation frequency, or bacterial-host biology. In conclusion, plasmids such as pCT have evolved to impose little impact on host strains. Therefore, the persistence of antibiotic resistance genes and their vectors is to be expected in the absence of antibiotic selective pressure regardless of antibiotic stewardship. Other means to reduce plasmid stability are needed to prevent the persistence of these vectors and the antibiotic resistance genes they carry.

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