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A Silkworm Infection Model for In Vivo Study of Glycopeptide Antibiotics

Glycopeptide antibiotics (GPAs) are drugs of last resort for treating infections by Gram-positive bacteria. They inhibit bacterial cell wall assembly by binding to the d-Ala-d-Ala terminus of peptidoglycan precursors, leading to cell lysis. Vancomycin and teicoplanin are first generation GPAs, while...

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Autores principales: Montali, Aurora, Berini, Francesca, Brivio, Maurizio Francesco, Mastore, Maristella, Saviane, Alessio, Cappellozza, Silvia, Marinelli, Flavia, Tettamanti, Gianluca
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7344559/
https://www.ncbi.nlm.nih.gov/pubmed/32512807
http://dx.doi.org/10.3390/antibiotics9060300
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author Montali, Aurora
Berini, Francesca
Brivio, Maurizio Francesco
Mastore, Maristella
Saviane, Alessio
Cappellozza, Silvia
Marinelli, Flavia
Tettamanti, Gianluca
author_facet Montali, Aurora
Berini, Francesca
Brivio, Maurizio Francesco
Mastore, Maristella
Saviane, Alessio
Cappellozza, Silvia
Marinelli, Flavia
Tettamanti, Gianluca
author_sort Montali, Aurora
collection PubMed
description Glycopeptide antibiotics (GPAs) are drugs of last resort for treating infections by Gram-positive bacteria. They inhibit bacterial cell wall assembly by binding to the d-Ala-d-Ala terminus of peptidoglycan precursors, leading to cell lysis. Vancomycin and teicoplanin are first generation GPAs, while dalbavancin is one of the few, recently approved, second generation GPAs. In this paper, we developed an in vivo insect model to compare, for the first time, the efficacy of these three GPAs in curing Staphylococcus aureus infection. Differently from previous reports, Bombyx mori larvae were reared at 37 °C, and the course of infection was monitored, following not only larval survival, but also bacterial load in the insect body, hemocyte activity, phenoloxidase activity, and antimicrobial peptide expression. We demonstrated that the injection of S. aureus into the hemolymph of B. mori larvae led to a marked reduction of their survival rate within 24–48 h. GPAs were not toxic to the larvae and cured S. aureus infection. Dalbavancin was more effective than first generation GPAs. Due to its great advantages (i.e., easy and safe handling, low rearing costs, low antibiotic amount needed for the tests, no restrictions imposed by ethical and regulatory issues), this silkworm infection model could be introduced in preclinical phases—prior to the use of mice—accelerating the discovery/development rate of novel GPAs.
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spelling pubmed-73445592020-07-09 A Silkworm Infection Model for In Vivo Study of Glycopeptide Antibiotics Montali, Aurora Berini, Francesca Brivio, Maurizio Francesco Mastore, Maristella Saviane, Alessio Cappellozza, Silvia Marinelli, Flavia Tettamanti, Gianluca Antibiotics (Basel) Article Glycopeptide antibiotics (GPAs) are drugs of last resort for treating infections by Gram-positive bacteria. They inhibit bacterial cell wall assembly by binding to the d-Ala-d-Ala terminus of peptidoglycan precursors, leading to cell lysis. Vancomycin and teicoplanin are first generation GPAs, while dalbavancin is one of the few, recently approved, second generation GPAs. In this paper, we developed an in vivo insect model to compare, for the first time, the efficacy of these three GPAs in curing Staphylococcus aureus infection. Differently from previous reports, Bombyx mori larvae were reared at 37 °C, and the course of infection was monitored, following not only larval survival, but also bacterial load in the insect body, hemocyte activity, phenoloxidase activity, and antimicrobial peptide expression. We demonstrated that the injection of S. aureus into the hemolymph of B. mori larvae led to a marked reduction of their survival rate within 24–48 h. GPAs were not toxic to the larvae and cured S. aureus infection. Dalbavancin was more effective than first generation GPAs. Due to its great advantages (i.e., easy and safe handling, low rearing costs, low antibiotic amount needed for the tests, no restrictions imposed by ethical and regulatory issues), this silkworm infection model could be introduced in preclinical phases—prior to the use of mice—accelerating the discovery/development rate of novel GPAs. MDPI 2020-06-04 /pmc/articles/PMC7344559/ /pubmed/32512807 http://dx.doi.org/10.3390/antibiotics9060300 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Montali, Aurora
Berini, Francesca
Brivio, Maurizio Francesco
Mastore, Maristella
Saviane, Alessio
Cappellozza, Silvia
Marinelli, Flavia
Tettamanti, Gianluca
A Silkworm Infection Model for In Vivo Study of Glycopeptide Antibiotics
title A Silkworm Infection Model for In Vivo Study of Glycopeptide Antibiotics
title_full A Silkworm Infection Model for In Vivo Study of Glycopeptide Antibiotics
title_fullStr A Silkworm Infection Model for In Vivo Study of Glycopeptide Antibiotics
title_full_unstemmed A Silkworm Infection Model for In Vivo Study of Glycopeptide Antibiotics
title_short A Silkworm Infection Model for In Vivo Study of Glycopeptide Antibiotics
title_sort silkworm infection model for in vivo study of glycopeptide antibiotics
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7344559/
https://www.ncbi.nlm.nih.gov/pubmed/32512807
http://dx.doi.org/10.3390/antibiotics9060300
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