Biofilm Microenvironment Activated Antibiotic Adjuvant for Implant-Associated Infections by Systematic Iron Metabolism Interference
© 2024 The Authors. Advanced Science published by Wiley-VCH GmbH..
Hematoma, a risk factor of implant-associated infections (IAIs), creates a Fe-rich environment following implantation, which proliferates the growth of pathogenic bacteria. Fe metabolism is a major vulnerability for pathogens and is crucial for several fundamental physiological processes. Herein, a deferiprone (DFP)-loaded layered double hydroxide (LDH)-based nanomedicine (DFPGa-LDH) that targets the Fe-rich environments of IAIs is reported. In response to acidic changes at the infection site, DFP@Ga-LDH systematically interferes with bacterial Fe metabolism via the substitution of Ga3+ and Fe scavenging by DFP. DFP@Ga-LDH effectively reverses the Fe/Ga ratio in Pseudomonas aeruginosa, causing comprehensive interference in various Fe-associated targets, including transcription and substance metabolism. In addition to its favorable antibacterial properties, DFP@Ga-LDH functions as a nano-adjuvant capable of delaying the emergence of antibiotic resistance. Accordingly, DFP@Ga-LDH is loaded with a siderophore antibiotic (cefiderocol, Cefi) to achieve the antibacterial nanodrug DFP@Ga-LDH-Cefi. Antimicrobial and biosafety efficacies of DFP@Ga-LDH-Cefi are validated using ex vivo human skin and mouse IAI models. The pivotal role of the hematoma-created Fe-rich environment of IAIs is highlighted, and a nanoplatform that efficiently interferes with bacterial Fe metabolism is developed. The findings of the study provide promising guidance for future research on the exploration of nano-adjuvants as antibacterial agents.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2024 |
|---|---|
| Enthalten in: |
Advanced science (Weinheim, Baden-Wurttemberg, Germany) - (2024) vom: 26. Feb., Seite e2400862 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Ding, Jianing [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Antibiotic adjuvant |
|---|
| Anmerkungen: |
Date Revised 26.02.2024 published: Print-Electronic Citation Status Publisher |
|---|
| doi: |
10.1002/advs.202400862 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM368981053 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM368981053 | ||
| 003 | DE-627 | ||
| 005 | 20240229165121.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240229s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1002/advs.202400862 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1309.xml |
| 035 | |a (DE-627)NLM368981053 | ||
| 035 | |a (NLM)38408138 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Ding, Jianing |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Biofilm Microenvironment Activated Antibiotic Adjuvant for Implant-Associated Infections by Systematic Iron Metabolism Interference |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Revised 26.02.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status Publisher | ||
| 520 | |a © 2024 The Authors. Advanced Science published by Wiley-VCH GmbH. | ||
| 520 | |a Hematoma, a risk factor of implant-associated infections (IAIs), creates a Fe-rich environment following implantation, which proliferates the growth of pathogenic bacteria. Fe metabolism is a major vulnerability for pathogens and is crucial for several fundamental physiological processes. Herein, a deferiprone (DFP)-loaded layered double hydroxide (LDH)-based nanomedicine (DFPGa-LDH) that targets the Fe-rich environments of IAIs is reported. In response to acidic changes at the infection site, DFP@Ga-LDH systematically interferes with bacterial Fe metabolism via the substitution of Ga3+ and Fe scavenging by DFP. DFP@Ga-LDH effectively reverses the Fe/Ga ratio in Pseudomonas aeruginosa, causing comprehensive interference in various Fe-associated targets, including transcription and substance metabolism. In addition to its favorable antibacterial properties, DFP@Ga-LDH functions as a nano-adjuvant capable of delaying the emergence of antibiotic resistance. Accordingly, DFP@Ga-LDH is loaded with a siderophore antibiotic (cefiderocol, Cefi) to achieve the antibacterial nanodrug DFP@Ga-LDH-Cefi. Antimicrobial and biosafety efficacies of DFP@Ga-LDH-Cefi are validated using ex vivo human skin and mouse IAI models. The pivotal role of the hematoma-created Fe-rich environment of IAIs is highlighted, and a nanoplatform that efficiently interferes with bacterial Fe metabolism is developed. The findings of the study provide promising guidance for future research on the exploration of nano-adjuvants as antibacterial agents | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a antibiotic adjuvant | |
| 650 | 4 | |a biofilm | |
| 650 | 4 | |a implant-associated infection | |
| 650 | 4 | |a iron metabolism interference | |
| 700 | 1 | |a Wang, Xin |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Wei |e verfasserin |4 aut | |
| 700 | 1 | |a Ding, Cheng |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Jianrong |e verfasserin |4 aut | |
| 700 | 1 | |a He, Renke |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Xianlong |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Advanced science (Weinheim, Baden-Wurttemberg, Germany) |d 2014 |g (2024) vom: 26. Feb., Seite e2400862 |w (DE-627)NLM252851455 |x 2198-3844 |7 nnns |
| 773 | 1 | 8 | |g year:2024 |g day:26 |g month:02 |g pages:e2400862 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1002/advs.202400862 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |j 2024 |b 26 |c 02 |h e2400862 | ||