Pluronic-based nano-self-assemblies of bacitracin A with a new mechanism of action for an efficient in vivo therapeutic effect against bacterial peritonitis
Abstract Background Although assemblies of hydrophobic-modified bacitracin A with PLGA (Nano-BAPLGA) have demonstrated promising antibacterial activities against both Gram-positive and Gram-negative bacteria, the desirable antibacterial potency has remained challenging due to the low solubility of N...
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BioMed Central
2018-09-01
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| Series: | Journal of Nanobiotechnology |
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| Online Access: | http://link.springer.com/article/10.1186/s12951-018-0397-3 |
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doaj-art-406416160b1e4d29a86cfb00f3b699952018-09-16T11:09:13ZengBioMed CentralJournal of Nanobiotechnology1477-31552018-09-0116111710.1186/s12951-018-0397-3Pluronic-based nano-self-assemblies of bacitracin A with a new mechanism of action for an efficient in vivo therapeutic effect against bacterial peritonitisWei Hong0Lipeng Liu1Yining Zhao2Yinghui Liu3Dexian Zhang4Mingchun Liu5Key Laboratory of Zoonosis of Liaoning Province, College of Animal Science and Veterinary Medicine, Shenyang Agricultural UniversityKey Laboratory of Zoonosis of Liaoning Province, College of Animal Science and Veterinary Medicine, Shenyang Agricultural UniversityKey Laboratory of Zoonosis of Liaoning Province, College of Animal Science and Veterinary Medicine, Shenyang Agricultural UniversityKey Laboratory of Zoonosis of Liaoning Province, College of Animal Science and Veterinary Medicine, Shenyang Agricultural UniversityKey Laboratory of Zoonosis of Liaoning Province, College of Animal Science and Veterinary Medicine, Shenyang Agricultural UniversityKey Laboratory of Zoonosis of Liaoning Province, College of Animal Science and Veterinary Medicine, Shenyang Agricultural UniversityAbstract Background Although assemblies of hydrophobic-modified bacitracin A with PLGA (Nano-BAPLGA) have demonstrated promising antibacterial activities against both Gram-positive and Gram-negative bacteria, the desirable antibacterial potency has remained challenging due to the low solubility of Nano-BAPLGA. To address this tissue, a series of Pluronic copolymers (Pluronic® F127, Pluronic® P123 and Pluronic® P85) were selected to link the N-terminus of bacitracin A to construct Pluronic-based nano-self assemblies (Nano-BAF127, Nano-BAP123 and Nano-BAP85). Results Impressively, all the newly designed Pluronic-based Nano-BAs possessed higher solubility and stronger effectiveness against both Gram-positive and Gram-negative bacteria compared with Nano-BAPLGA, especially the modification with Pluronic® P85. Surface tension measurements indicated that Nano-BAP85 was much more tensioactive than Nano-BAPLGA, which usually translated into a good membranolytic effect. Fluorescence spectroscopy and electron microscopy analyses confirmed the speculation that the cell wall/membrane might be the main action target of Nano-BAP85 by permeabilizing the cell membrane and damaging the membrane integrity. In vivo results further demonstrated that Nano-BAP85 significantly suppressed bacterial growth and prolonged survival time in the bacterial peritonitis mouse model with negligible toxicity. Conclusions Collectively, the membrane targeting mechanism of action is entirely distinct from those of clinically used antibacterial agents. Furthermore, the new approach of construction nanoantibiotics based on the modification of commercially available antibiotics with Pluronic copolymers is demonstrated to have an efficient therapeutic effect against bacterial infection.http://link.springer.com/article/10.1186/s12951-018-0397-3Pluronic-based Nano-BAsNano-BAP85TensioactiveMembranolytic effectEfficient therapeutic effect |
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| language |
English |
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Article |
| author |
Wei Hong Lipeng Liu Yining Zhao Yinghui Liu Dexian Zhang Mingchun Liu |
| spellingShingle |
Wei Hong Lipeng Liu Yining Zhao Yinghui Liu Dexian Zhang Mingchun Liu Pluronic-based nano-self-assemblies of bacitracin A with a new mechanism of action for an efficient in vivo therapeutic effect against bacterial peritonitis Journal of Nanobiotechnology Pluronic-based Nano-BAs Nano-BAP85 Tensioactive Membranolytic effect Efficient therapeutic effect |
| author_facet |
Wei Hong Lipeng Liu Yining Zhao Yinghui Liu Dexian Zhang Mingchun Liu |
| author_sort |
Wei Hong |
| title |
Pluronic-based nano-self-assemblies of bacitracin A with a new mechanism of action for an efficient in vivo therapeutic effect against bacterial peritonitis |
| title_short |
Pluronic-based nano-self-assemblies of bacitracin A with a new mechanism of action for an efficient in vivo therapeutic effect against bacterial peritonitis |
| title_full |
Pluronic-based nano-self-assemblies of bacitracin A with a new mechanism of action for an efficient in vivo therapeutic effect against bacterial peritonitis |
| title_fullStr |
Pluronic-based nano-self-assemblies of bacitracin A with a new mechanism of action for an efficient in vivo therapeutic effect against bacterial peritonitis |
| title_full_unstemmed |
Pluronic-based nano-self-assemblies of bacitracin A with a new mechanism of action for an efficient in vivo therapeutic effect against bacterial peritonitis |
| title_sort |
pluronic-based nano-self-assemblies of bacitracin a with a new mechanism of action for an efficient in vivo therapeutic effect against bacterial peritonitis |
| publisher |
BioMed Central |
| series |
Journal of Nanobiotechnology |
| issn |
1477-3155 |
| publishDate |
2018-09-01 |
| description |
Abstract Background Although assemblies of hydrophobic-modified bacitracin A with PLGA (Nano-BAPLGA) have demonstrated promising antibacterial activities against both Gram-positive and Gram-negative bacteria, the desirable antibacterial potency has remained challenging due to the low solubility of Nano-BAPLGA. To address this tissue, a series of Pluronic copolymers (Pluronic® F127, Pluronic® P123 and Pluronic® P85) were selected to link the N-terminus of bacitracin A to construct Pluronic-based nano-self assemblies (Nano-BAF127, Nano-BAP123 and Nano-BAP85). Results Impressively, all the newly designed Pluronic-based Nano-BAs possessed higher solubility and stronger effectiveness against both Gram-positive and Gram-negative bacteria compared with Nano-BAPLGA, especially the modification with Pluronic® P85. Surface tension measurements indicated that Nano-BAP85 was much more tensioactive than Nano-BAPLGA, which usually translated into a good membranolytic effect. Fluorescence spectroscopy and electron microscopy analyses confirmed the speculation that the cell wall/membrane might be the main action target of Nano-BAP85 by permeabilizing the cell membrane and damaging the membrane integrity. In vivo results further demonstrated that Nano-BAP85 significantly suppressed bacterial growth and prolonged survival time in the bacterial peritonitis mouse model with negligible toxicity. Conclusions Collectively, the membrane targeting mechanism of action is entirely distinct from those of clinically used antibacterial agents. Furthermore, the new approach of construction nanoantibiotics based on the modification of commercially available antibiotics with Pluronic copolymers is demonstrated to have an efficient therapeutic effect against bacterial infection. |
| topic |
Pluronic-based Nano-BAs Nano-BAP85 Tensioactive Membranolytic effect Efficient therapeutic effect |
| url |
http://link.springer.com/article/10.1186/s12951-018-0397-3 |
| _version_ |
1612573816144265216 |