Efficacy of Ceftobiprole Medocaril against Enterococcus faecalis in a Murine Urinary Tract Infection Model

Singh, Kavindra V.; Murray, Barbara E.

doi:10.1128/aac.06102-11

Cited by 9 publications

(8 citation statements)

References 34 publications

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“…The authors observed 5log bacterial reductions in high concentration (50 mg/kg) of β -lactam derivatives. This reduction was very significant in animal models when compared with the earlier reports, where ampicillin (50 mg/kg) was used in the same infectious model [ 45 ]. The reduction by compound 3 in intravenous model was observed to be better than daptomycin in intravenous model reported earlier [ 46 ].…”

Section: Discussionmentioning

confidence: 82%

Bioactivity Studies of β-Lactam Derived Polycyclic Fused Pyrroli-Dine/Pyrrolizidine Derivatives in Dentistry: In Vitro, In Vivo and In Silico Studies

et al. 2015

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The antibacterial activity of β-lactam derived polycyclic fused pyrrolidine/pyrrolizidine derivatives synthesized by 1, 3-dipolar cycloaddition reaction was evaluated against microbes involved in dental infection. Fifteen compounds were screened; among them compound 3 showed efficient antibacterial activity in an ex vivo dentinal tubule model and in vivo mice infectious model. In silico docking studies showed greater affinity to penicillin binding protein. Cell damage was observed under Scanning Electron Microscopy (SEM) which was further proved by Confocal Laser Scanning Microscope (CLSM) and quantified using Flow Cytometry by PI up-take. Compound 3 treated E. faecalis showed ROS generation and loss of membrane integrity was quantified by flow cytometry. Compound 3 was also found to be active against resistant E. faecalis strains isolated from failed root canal treatment cases. Further, compound 3 was found to be hemocompatible, not cytotoxic to normal mammalian NIH 3T3 cells and non mutagenic. It was concluded that β-lactam compound 3 exhibited promising antibacterial activity against E. faecalis involved in root canal infections and the mechanism of action was deciphered. The results of this research can be further implicated in the development of potent antibacterial medicaments with applications in dentistry.

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Section: Discussionmentioning

confidence: 82%

Bioactivity Studies of β-Lactam Derived Polycyclic Fused Pyrroli-Dine/Pyrrolizidine Derivatives in Dentistry: In Vitro, In Vivo and In Silico Studies

et al. 2015

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“…It is possible that CspR may be one of the 'moonlighting' protein group, meaning that it can have two unrelated functions according to its intra-or extracellular location. To date, for the prevention of E. faecalis infections, in addition to lipoteichoic acid and capsular polysaccharides, three proteins known as virulence factors have been proposed as possible immunotherapy targets: the general stress protein Gls24, the collagen adhesion Ace, and the endocarditis-and biofilm-associated pilus Ebp (Giard et al, 2000;Huebner et al, 2000;Lebreton et al, 2009;Murray, 1990;Singh & Murray, 2012;Singh et al, 2007;Teng et al, 2005). Our results showed that a cold-shock RNA-binding protein can present a double localization, both intercellularly and at the surface of the bacteria, and that anti-CspR antibody protects insect larvae against infection by E. faecalis.…”

Section: Discussionmentioning

confidence: 99%

Cold-shock RNA-binding protein CspR is also exposed to the surface of Enterococcus faecalis

et al. 2013

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CspR has been characterized recently as a cold-shock RNA-binding protein in Enterococcus faecalis, a natural member of the gastro-intestinal tract capable of switching from a commensal relationship with the host to an important nosocomial pathogen. In addition to its involvement in the cold-shock response, CspR also plays a role in the long-term survival and virulence of E. faecalis. In the present study, we demonstrated that anti-CspR immune rabbit serum protected larvae of Galleria mellonella against a lethal challenge of the WT strain. These results suggested that CspR might have a surface location. This hypothesis was verified by Western blot that showed detection of CspR in the total as well as in the surface protein fraction. In addition, identification of surface polypeptides by proteolytic shaving of intact bacterial cells followed by liquid chromatography-MS-MS revealed that cold-shock proteins (EF1367, EF2939 and CspR) were present on the cell surface. Lastly, anti-CspR immune rabbit serum was used for immunolabelling and detected with colloidal gold-labelled goat anti-rabbit IgG in order to determine the immunolocalization of CspR on E. faecalis WT strain. Electron microscopy images confirmed that the cold-shock protein RNA-binding protein CspR was present in both cytoplasmic and surface parts of the cell. These data strongly suggest that CspR, in addition to being located intracellularly, is also present in the extracellular protein fraction of the cells and has important functions in the infection process of Galleria larvae. INTRODUCTIONEnterococcus faecalis, a natural member of the intestinal tract, is versatile and can switch from a commensal relationship with the host to a leading cause of nosocomial infections (Murray, 1990;Sreeja et al., 2012; Wisplinghoff et al., 2004). This bacterium, well known to be able to cope with hostile environments (Ogier & Serror, 2008) and used as an indicator of faecal contamination, is responsible for serious infections such as endocarditis or surgical wound infection, especially in immunocompromised patients Shepard & Gilmore, 2002). Therefore, the virulence of E. faecalis has been intensively studied over the past 20 years and~12 putative virulence genes have been reported, including several transcriptional and post-transcriptional regulators. The recently identified cold-shock RNA-binding protein CspR is part of this last category of virulence-associated factors (Fox et al., 2009;Hancock & Gilmore, 2002;Lebreton et al., 2009;Michaux et al., 2011 Michaux et al., , 2012Qin et al., 2001; Shankar et al., 2001). In some Gram-positive bacteria such as Staphylococcus aureus and Bacillus subtilis, cold-shock polypeptides have been shown to be involved in several aspects of bacterial life, i.e. survival under starvation and low-temperature conditions or resistance to anti-microbial agents (Duval et al., 2010;Graumann & Marahiel, 1999, 1996 Graumann et al., 1997). In addition, the cold-shock polypeptides usually present the conserved RNA-binding motifs RNP-1 and RNP-...

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“…Food and water were allowed ad libitum. Literature was used to design in-house pharmacokinetic studies [58][59][60] and results from those studies were used to select dosing concentrations and intervals for the present study in which amp and cipro were given twice daily at 8-h intervals and fosfo was given once daily for three consecutive days. Fecal samples were collected at euthanasia from the distal ileum and proximal colon after 24 h (1 day), 48 h (2 days) and 72 h (3 days) of treatment.…”

Section: Animal Model and Antibiotic Exposurementioning

confidence: 99%

The effect of antibiotics on the gut microbiome: a metagenomics analysis of microbial shift and gut antibiotic resistance in antibiotic treated mice

Surathu

Raplee

et al. 2020

BMC Genomics

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Background: Emergence of antibiotic resistance is a global public health concern. The relationships between antibiotic use, the gut community composition, normal physiology and metabolism, and individual and public health are still being defined. Shifts in composition of bacteria, antibiotic resistance genes (ARGs) and mobile genetic elements (MGEs) after antibiotic treatment are not well-understood. Methods: This project used next-generation sequencing, custom-built metagenomics pipeline and differential abundance analysis to study the effect of antibiotic monotherapy on resistome and taxonomic composition in the gut of Balb/c mice infected with E. coli via transurethral catheterization to investigate the evolution and emergence of antibiotic resistance. Results: There is a longitudinal decrease of gut microbiota diversity after antibiotic treatment. Various ARGs are enriched within the gut microbiota despite an overall reduction of the diversity and total amount of bacteria after antibiotic treatment. Sometimes treatment with a specific class of antibiotics selected for ARGs that resist antibiotics of a completely different class (e.g. treatment of ciprofloxacin or fosfomycin selected for cepA that resists ampicillin). Relative abundance of some MGEs increased substantially after antibiotic treatment (e.g. transposases in the ciprofloxacin group). Conclusions: Antibiotic treatment caused a remarkable reduction in diversity of gut bacterial microbiota but enrichment of certain types of ARGs and MGEs. These results demonstrate an emergence of cross-resistance as well as a profound change in the gut resistome following oral treatment of antibiotics.

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Efficacy of Ceftobiprole Medocaril against Enterococcus faecalis in a Murine Urinary Tract Infection Model

Cited by 9 publications

References 34 publications

Bioactivity Studies of β-Lactam Derived Polycyclic Fused Pyrroli-Dine/Pyrrolizidine Derivatives in Dentistry: In Vitro, In Vivo and In Silico Studies

Bioactivity Studies of β-Lactam Derived Polycyclic Fused Pyrroli-Dine/Pyrrolizidine Derivatives in Dentistry: In Vitro, In Vivo and In Silico Studies

Cold-shock RNA-binding protein CspR is also exposed to the surface of Enterococcus faecalis

The effect of antibiotics on the gut microbiome: a metagenomics analysis of microbial shift and gut antibiotic resistance in antibiotic treated mice

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