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 <span style="font-variant: small-caps;">d</span>-Ala-<span style="font-variant: small-caps;">d...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-06-01
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| Series: | Antibiotics |
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| Online Access: | https://www.mdpi.com/2079-6382/9/6/300 |
| _version_ | 1827715665560076288 |
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| author | Aurora Montali Francesca Berini Maurizio Francesco Brivio Maristella Mastore Alessio Saviane Silvia Cappellozza Flavia Marinelli Gianluca Tettamanti |
| author_facet | Aurora Montali Francesca Berini Maurizio Francesco Brivio Maristella Mastore Alessio Saviane Silvia Cappellozza Flavia Marinelli Gianluca Tettamanti |
| author_sort | Aurora Montali |
| collection | DOAJ |
| 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 <span style="font-variant: small-caps;">d</span>-Ala-<span style="font-variant: small-caps;">d</span>-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 <i>Staphylococcus aureus</i> infection. Differently from previous reports, <i>Bombyx mori</i> 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 <i>S. aureus</i> into the hemolymph of <i>B. mori</i> larvae led to a marked reduction of their survival rate within 24–48 h. GPAs were not toxic to the larvae and cured <i>S. aureus</i> 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. |
| first_indexed | 2024-03-10T19:23:09Z |
| format | Article |
| id | doaj.art-c2e4375bb4264df2b17744433e7c6226 |
| institution | Directory Open Access Journal |
| issn | 2079-6382 |
| language | English |
| last_indexed | 2024-03-10T19:23:09Z |
| publishDate | 2020-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antibiotics |
| spelling | doaj.art-c2e4375bb4264df2b17744433e7c62262023-11-20T02:50:46ZengMDPI AGAntibiotics2079-63822020-06-019630010.3390/antibiotics9060300A Silkworm Infection Model for In Vivo Study of Glycopeptide AntibioticsAurora Montali0Francesca Berini1Maurizio Francesco Brivio2Maristella Mastore3Alessio Saviane4Silvia Cappellozza5Flavia Marinelli6Gianluca Tettamanti7Department of Biotechnology and Life Sciences, University of Insubria, 21100 Varese, ItalyDepartment of Biotechnology and Life Sciences, University of Insubria, 21100 Varese, ItalyDepartment of Theoretical and Applied Sciences, University of Insubria, 21100 Varese, ItalyDepartment of Theoretical and Applied Sciences, University of Insubria, 21100 Varese, ItalyCouncil for Agricultural Research and Economics, Research Centre for Agriculture and Environment (CREA-AA), 35143 Padova, ItalyCouncil for Agricultural Research and Economics, Research Centre for Agriculture and Environment (CREA-AA), 35143 Padova, ItalyDepartment of Biotechnology and Life Sciences, University of Insubria, 21100 Varese, ItalyDepartment of Biotechnology and Life Sciences, University of Insubria, 21100 Varese, ItalyGlycopeptide antibiotics (GPAs) are drugs of last resort for treating infections by Gram-positive bacteria. They inhibit bacterial cell wall assembly by binding to the <span style="font-variant: small-caps;">d</span>-Ala-<span style="font-variant: small-caps;">d</span>-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 <i>Staphylococcus aureus</i> infection. Differently from previous reports, <i>Bombyx mori</i> 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 <i>S. aureus</i> into the hemolymph of <i>B. mori</i> larvae led to a marked reduction of their survival rate within 24–48 h. GPAs were not toxic to the larvae and cured <i>S. aureus</i> 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.https://www.mdpi.com/2079-6382/9/6/300insect infection model<i>Bombyx mori</i>glycopeptide antibioticsvancomycinteicoplanindalbavancin |
| spellingShingle | Aurora Montali Francesca Berini Maurizio Francesco Brivio Maristella Mastore Alessio Saviane Silvia Cappellozza Flavia Marinelli Gianluca Tettamanti A Silkworm Infection Model for In Vivo Study of Glycopeptide Antibiotics Antibiotics insect infection model <i>Bombyx mori</i> glycopeptide antibiotics vancomycin teicoplanin dalbavancin |
| 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 | insect infection model <i>Bombyx mori</i> glycopeptide antibiotics vancomycin teicoplanin dalbavancin |
| url | https://www.mdpi.com/2079-6382/9/6/300 |
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