Enzymatically-crosslinked gelatin hydrogels containing paenipeptin and clarithromycin against carbapenem-resistant pathogen in murine skin wound infection
Abstract Background The recent rise and spread of carbapenem-resistant pathogens pose an urgent threat to public health and has fueled the search for new therapies. Localized delivery of topical antibiotics is an alternative for the treatment of infected wounds caused by drug-resistant pathogens. In...
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| Format: | Article |
| Language: | English |
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BMC
2021-11-01
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| Series: | BMC Microbiology |
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| Online Access: | https://doi.org/10.1186/s12866-021-02383-z |
| _version_ | 1818343073602600960 |
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| author | Sun Hee Moon Yihong Kaufmann Ryoichi Fujiwara En Huang |
| author_facet | Sun Hee Moon Yihong Kaufmann Ryoichi Fujiwara En Huang |
| author_sort | Sun Hee Moon |
| collection | DOAJ |
| description | Abstract Background The recent rise and spread of carbapenem-resistant pathogens pose an urgent threat to public health and has fueled the search for new therapies. Localized delivery of topical antibiotics is an alternative for the treatment of infected wounds caused by drug-resistant pathogens. In this study, we aimed to develop antimicrobial-loaded hydrogels for topical treatment of wound infections in a murine skin wound infection. Results Paenipeptin analogue 1, a linear lipopeptide, potentiated clarithromycin against multidrug-resistant Acinetobacter baumannii, Enterobacter cloacae, Escherichia coli, and Klebsiella pneumoniae. Enzymatically-crosslinked gelatin hydrogels were developed to encapsulate paenipeptin analogue 1 and clarithromycin. The encapsulated antimicrobials were gradually released from hydrogels during incubation, reaching 75.43 and 53.66% for paenipeptin and clarithromycin, respectively, at 24 h. The antimicrobial-loaded hydrogels containing paenipeptin and clarithromycin synergistically resulted in 5-log reduction in carbapenem-resistant A. baumannii within 6 h in vitro. Moreover, the antimicrobial-loaded hydrogels reduced 3.6- and 2.5-log of carbapenem-resistant A. baumannii when treated at 4 or 20 h post infection, respectively, in a murine skin wound infection. Conclusions Enzymatically-crosslinked gelatin hydrogels loaded with paenipeptin analogue 1 and clarithromycin exhibited potent therapeutic efficacy against carbapenem-resistant A. baumannii in murine skin wound infection. |
| first_indexed | 2024-12-13T16:24:47Z |
| format | Article |
| id | doaj.art-758f23ed699546a687f8130baee2590e |
| institution | Directory Open Access Journal |
| issn | 1471-2180 |
| language | English |
| last_indexed | 2024-12-13T16:24:47Z |
| publishDate | 2021-11-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Microbiology |
| spelling | doaj.art-758f23ed699546a687f8130baee2590e2022-12-21T23:38:38ZengBMCBMC Microbiology1471-21802021-11-012111710.1186/s12866-021-02383-zEnzymatically-crosslinked gelatin hydrogels containing paenipeptin and clarithromycin against carbapenem-resistant pathogen in murine skin wound infectionSun Hee Moon0Yihong Kaufmann1Ryoichi Fujiwara2En Huang3Department of Environmental and Occupational Health, University of Arkansas for Medical SciencesDepartment of Environmental and Occupational Health, University of Arkansas for Medical SciencesDepartment of Pharmaceutical Sciences, University of Arkansas for Medical SciencesDepartment of Environmental and Occupational Health, University of Arkansas for Medical SciencesAbstract Background The recent rise and spread of carbapenem-resistant pathogens pose an urgent threat to public health and has fueled the search for new therapies. Localized delivery of topical antibiotics is an alternative for the treatment of infected wounds caused by drug-resistant pathogens. In this study, we aimed to develop antimicrobial-loaded hydrogels for topical treatment of wound infections in a murine skin wound infection. Results Paenipeptin analogue 1, a linear lipopeptide, potentiated clarithromycin against multidrug-resistant Acinetobacter baumannii, Enterobacter cloacae, Escherichia coli, and Klebsiella pneumoniae. Enzymatically-crosslinked gelatin hydrogels were developed to encapsulate paenipeptin analogue 1 and clarithromycin. The encapsulated antimicrobials were gradually released from hydrogels during incubation, reaching 75.43 and 53.66% for paenipeptin and clarithromycin, respectively, at 24 h. The antimicrobial-loaded hydrogels containing paenipeptin and clarithromycin synergistically resulted in 5-log reduction in carbapenem-resistant A. baumannii within 6 h in vitro. Moreover, the antimicrobial-loaded hydrogels reduced 3.6- and 2.5-log of carbapenem-resistant A. baumannii when treated at 4 or 20 h post infection, respectively, in a murine skin wound infection. Conclusions Enzymatically-crosslinked gelatin hydrogels loaded with paenipeptin analogue 1 and clarithromycin exhibited potent therapeutic efficacy against carbapenem-resistant A. baumannii in murine skin wound infection.https://doi.org/10.1186/s12866-021-02383-zCarbapenem-resistanceWound infectionPaenipeptinClarithromycinHydrogel |
| spellingShingle | Sun Hee Moon Yihong Kaufmann Ryoichi Fujiwara En Huang Enzymatically-crosslinked gelatin hydrogels containing paenipeptin and clarithromycin against carbapenem-resistant pathogen in murine skin wound infection BMC Microbiology Carbapenem-resistance Wound infection Paenipeptin Clarithromycin Hydrogel |
| title | Enzymatically-crosslinked gelatin hydrogels containing paenipeptin and clarithromycin against carbapenem-resistant pathogen in murine skin wound infection |
| title_full | Enzymatically-crosslinked gelatin hydrogels containing paenipeptin and clarithromycin against carbapenem-resistant pathogen in murine skin wound infection |
| title_fullStr | Enzymatically-crosslinked gelatin hydrogels containing paenipeptin and clarithromycin against carbapenem-resistant pathogen in murine skin wound infection |
| title_full_unstemmed | Enzymatically-crosslinked gelatin hydrogels containing paenipeptin and clarithromycin against carbapenem-resistant pathogen in murine skin wound infection |
| title_short | Enzymatically-crosslinked gelatin hydrogels containing paenipeptin and clarithromycin against carbapenem-resistant pathogen in murine skin wound infection |
| title_sort | enzymatically crosslinked gelatin hydrogels containing paenipeptin and clarithromycin against carbapenem resistant pathogen in murine skin wound infection |
| topic | Carbapenem-resistance Wound infection Paenipeptin Clarithromycin Hydrogel |
| url | https://doi.org/10.1186/s12866-021-02383-z |
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