Toxicity evaluation for an Enterococcus faecium strain TM39 in vitro and in vivo

Abstract Background The combination of daptomycin (DAP) plus ampicillin (AMP), ertapenem (ERT), or ceftaroline has been demonstrated to be efficacious against a DAP-tolerant Enterococcus faecium strain (HOU503). However, the mechanism for the efficacy of these combinations against DAP-resistant (DAP-R) E. faecium strains is unknown. Methods We investigated the efficacy of DAP in combination with AMP, ERT, ceftaroline, ceftriaxone, or amoxicillin against DAP-R E. faecium R497 using established in vitro and in vivo models. We evaluated pbp expression, levels of penicillin-binding protein (PBP) 5 (PBP5) and β-lactam binding affinity in HOU503 versus R497. Results DAP plus AMP was the only efficacious regimen against DAP-R R497 and prevented emergence of resistance. DAP at 8, 6, and 4 mg/kg in combination with AMP was efficacious but showed delayed killing compared with 10 mg/kg. PBP5 of HOU503 exhibited amino acid substitutions in the penicillin-binding domain relative to R497. No difference in pbp mRNA or PBP5 levels was detected between HOU503 and R497. labeling of PBPs with Bocillin FL, a fluorescent penicillin derivative, showed increased β-lactam binding affinity of PBP5 of HOU503 compared with that of R497. Conclusions Only DAP (10 mg/kg) plus AMP or amoxicillin was efficacious against a DAP-R E. faecium strain, and pbp5 alleles may be important contributors to efficacy of DAP plus β-lactam therapy.

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In Vivo and In Vitro Toxicity Evaluation of Polyprenols Extracted from Ginkgo biloba L. Leaves

Molecules ◽

10.3390/molecules201219839 ◽

2015 ◽

Vol 20 (12) ◽

pp. 22257-22271 ◽

Cited By ~ 7

Author(s):

Cheng-Zhang Wang ◽

Jiao-Jiao Yuan ◽

Wen-Jun Li ◽

Hong-Yu Zhang ◽

Jian-Zhong Ye

Keyword(s):

Ginkgo Biloba ◽

In Vitro Toxicity ◽

Toxicity Evaluation

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The photodynamic activity and toxicity evaluation of 5,10,15-tris(ethoxylcarbonyl)corrole phosphorus(V) in vivo and in vitro

European Journal of Medicinal Chemistry ◽

10.1016/j.ejmech.2018.12.031 ◽

2019 ◽

Vol 163 ◽

pp. 779-786 ◽

Cited By ~ 7

Author(s):

Zhao Zhang ◽

Hua-Jun Yu ◽

Hui Huang ◽

Hua-Hua Wang ◽

Shang Wu ◽

...

Keyword(s):

Toxicity Evaluation ◽

Photodynamic Activity

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Synthesis, characterization, in vitro SAR study, and preliminary in vivo toxicity evaluation of naphthylmethyl substituted bis-imidazolium salts

Bioorganic & Medicinal Chemistry ◽

10.1016/j.bmc.2020.115893 ◽

2021 ◽

Vol 30 ◽

pp. 115893

Author(s):

Marie R. Southerland ◽

Michael A. DeBord ◽

Nicholas A. Johnson ◽

Steven R. Crabtree ◽

Nicolas E. Alexander ◽

...

Keyword(s):

Imidazolium Salts ◽

Toxicity Evaluation ◽

In Vivo Toxicity ◽

Sar Study

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In vitro cytotoxicity and in vivo zebrafish toxicity evaluation of Ru(ii)/2-mercaptopyrimidine complexes

Dalton Transactions ◽

10.1039/c8dt03738h ◽

2019 ◽

Vol 48 (18) ◽

pp. 6026-6039 ◽

Cited By ~ 6

Author(s):

Vivianne S. Velozo-Sá ◽

Luciano R. Pereira ◽

Aliny P. Lima ◽

Francyelli Mello-Andrade ◽

Manuela R. M. Rezende ◽

...

Keyword(s):

Cancer Cells ◽

Larval Development ◽

In Vitro Cytotoxicity ◽

Toxic Effects ◽

Toxicity Evaluation ◽

Embryonic And Larval Development

Ru(ii)/2-mercaptopyrimidine complexes active against cancer cells did not present toxic effects during embryonic and larval development of zebrafish.

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In vitro and in vivo toxicity evaluation of non-neuroleptic phenothiazines, antitubercular drug candidates

Regulatory Toxicology and Pharmacology ◽

10.1016/j.yrtph.2019.104508 ◽

2019 ◽

Vol 109 ◽

pp. 104508 ◽

Cited By ~ 1

Author(s):

Sumayah Salie ◽

Antoinette Labuschagné ◽

Avril Walters ◽

Sohair Geyer ◽

Anwar Jardine ◽

...

Keyword(s):

Antitubercular Drug ◽

Toxicity Evaluation ◽

In Vivo Toxicity ◽

Drug Candidates

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Effects of the probiotic Enterococcus faecium NCIMB 10415 on selected lactic acid bacteria and enterobacteria in co-culture

Beneficial Microbes ◽

10.3920/bm2014.0052 ◽

2015 ◽

Vol 6 (3) ◽

pp. 345-352 ◽

Cited By ~ 9

Author(s):

I.C. Starke ◽

J. Zentek ◽

W. Vahjen

Keyword(s):

Intestinal Microbiota ◽

Enterococcus Faecium ◽

Lactobacillus Reuteri ◽

Specific Growth ◽

Probiotic Strain ◽

Lactobacillus Mucosae ◽

Vitro Effect ◽

Reference Strains ◽

Faecium Strain

Enterococcus faecium NCIMB 10415 is used as a probiotic for piglets and has been shown to modify the porcine intestinal microbiota. However, the mode of action of this probiotic modification is still unclear. One possible explanation is the direct growth inhibiting or stimulating effect of the probiotic on other indigenous bacteria. Therefore, the aim of the present study was to examine the growth interactions of the probiotic with different indigenous porcine bacteria in vitro. Reference strains were cultivated with the probiotic E. faecium strain NCIMB10415 (SF68) in a checkerboard assay with 102 to 105 cells/ml inoculum per strain. Growth kinetics were recorded for 8 h and used to determine specific growth of the co-cultures. Additionally, total DNA was extracted from the co-cultures at the end of the incubation to verify which strain in the co-culture was affected. Co-cultivation with eight Enterococcus spp. tester strains showed strain-specific growth differences. Three of four E. faecium strains were not influenced by the probiotic strain. PCR results showed reduced growth of the probiotic strain in co-culture with E. faecium DSM 6177. Three of four Enterococcus faecalis strains showed reduced specific growth in co-culture with the probiotic strain. However, E. faecalis DSM 20478 impaired growth of the probiotic E. faecium strain. The growth of Lactobacillus johnsonii DSM 10533 and Lactobacillus reuteri DSM 20016 was enhanced in co-culture with the probiotic strain, but co-cultivations with Lactobacillus mucosae DSM13345 or Lactobacillus amylovorus DSM10533 showed no differences. Co-cultures with the probiotic E. faecium showed no impact on the growth rate of four different enterobacterial reference strains (2 strains of Salmonella enterica and 2 strains of Escherichia coli), but PCR results showed reduced cell numbers for a pathogenic E. coli isolate at higher concentration of the probiotic strain. As the in vitro effect of the probiotic E. faecium on enterococci was strain specific and the growth of certain Lactobacillus spp. was enhanced by the probiotic, these results indicate a direct effect of the probiotic on certain members of the porcine gastro intestinal microbiota.

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In vitro and in vivo toxicity evaluation of plant virus nanocarriers

Colloids and Surfaces B Biointerfaces ◽

10.1016/j.colsurfb.2015.03.039 ◽

2015 ◽

Vol 129 ◽

pp. 130-136 ◽

Cited By ~ 16

Author(s):

Agnese Blandino ◽

Chiara Lico ◽

Selene Baschieri ◽

Lanfranco Barberini ◽

Carlo Cirotto ◽

...

Keyword(s):

Plant Virus ◽

Toxicity Evaluation ◽

In Vivo Toxicity

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Genetic Basis forIn VitroandIn VivoResistance to Lincosamides, Streptogramins A, and Pleuromutilins (LSAP Phenotype) in Enterococcus faecium

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01030-13 ◽

2013 ◽

Vol 57 (9) ◽

pp. 4463-4469 ◽

Cited By ~ 28

Author(s):

Christophe Isnard ◽

Brigitte Malbruny ◽

Roland Leclercq ◽

Vincent Cattoir

Keyword(s):

Amino Acid ◽

Molecular Mechanism ◽

Enterococcus Faecium ◽

Full Genome Sequence ◽

Comparative Genomic ◽

Content Type ◽

Abc Protein

ABSTRACTAs opposed toEnterococcus faecalis, which is intrinsically resistant to lincosamides, streptogramins A, and pleuromutilins (LSAP phenotype) by production of the ABC protein Lsa(A),Enterococcus faeciumis naturally susceptible. Since this phenotype may be selected forin vivoby quinupristin-dalfopristin (Q-D), the aim of this study was to investigate the molecular mechanism of acquired LSAP resistance inE. faecium. Six LSAP-resistantin vitromutants ofE. faeciumHM1070 as well as three different pairs of clinical isolates (pre- and postexposure to Q-D) were studied. The full genome sequence of anin vitromutant (E. faeciumUCN90B) was determined by using 454 sequencing technology and was compared with that of the parental strain. Single-nucleotide replacement was carried out to confirm the role of this mutation. By comparative genomic analysis, a point mutation was found within a 1,503-bp gene coding for an ABC homologue showing 66% amino acid identity with Lsa(A). This mutation (C1349T) led to an amino acid substitution (Thr450Ile). An identical mutation was identified in allin vitroandin vivoresistant strains but was not present in susceptible strains. The wild-type allele was namedeat(A) (forEnterococcusABCtransporter), and its mutated allelic variant was namedeat(A)v. The introduction ofeat(A)vfrom UCN90B into HM1070 conferred the LSAP phenotype, whereas that ofeat(A) from HM1070 into UCN90B restored susceptibility entirely. This is the first description of the molecular mechanism of acquired LSAP resistance inE. faecium. Characterization of the biochemical mechanism of resistance and the physiological role of this ABC protein need further investigations.

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