Cargando…

Antimicrobial Peptide Cec4 Eradicates Multidrug-Resistant Acinetobacter baumannii in vitro and in vivo

INTRODUCTION: Acinetobacter baumannii has become a major difficulty in the treatment of bacteria-associated infection. The previously reported antimicrobial peptide Cec4 exhibited good and stable activity against A. baumannii in vitro, but the mechanisms and effects in vivo are elusive. METHODS: The...

Descripción completa

Detalles Bibliográficos
Autores principales: Peng, Jian, Wang, Yue, Wu, Zhaoyin, Mao, Chengju, Li, Lu, Cao, Huijun, Qiu, Zhilang, Guo, Guo, Liang, Guiyou, Shen, Feng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10069437/
https://www.ncbi.nlm.nih.gov/pubmed/37020803
http://dx.doi.org/10.2147/DDDT.S405579
_version_ 1785018847264243712
author Peng, Jian
Wang, Yue
Wu, Zhaoyin
Mao, Chengju
Li, Lu
Cao, Huijun
Qiu, Zhilang
Guo, Guo
Liang, Guiyou
Shen, Feng
author_facet Peng, Jian
Wang, Yue
Wu, Zhaoyin
Mao, Chengju
Li, Lu
Cao, Huijun
Qiu, Zhilang
Guo, Guo
Liang, Guiyou
Shen, Feng
author_sort Peng, Jian
collection PubMed
description INTRODUCTION: Acinetobacter baumannii has become a major difficulty in the treatment of bacteria-associated infection. The previously reported antimicrobial peptide Cec4 exhibited good and stable activity against A. baumannii in vitro, but the mechanisms and effects in vivo are elusive. METHODS: The effects of Cec4 on bacterial membrane permeability, membrane potential and bacterial reactive oxygen species were measured. The cell membrane localization of antimicrobial peptides was studied by fluorescence labelling. The ability of bacteria to develop resistance to antimicrobial peptides was studied by continuous induction, and transcriptome difference was analysed. The in vivo toxicity of Cec4 against nematodes and mice was studied, and the in vivo therapeutic potential of Cec4 against A. baumannii was assessed. RESULTS: Cec4 effectively cleared multidrug-resistant A. baumannii by altering bacterial cell membrane permeability, changing bacterial cell membrane polarity, and increasing bacterial intracellular reactive oxygen species. Cec4 affected the expression of the secretion system, outer membrane, and efflux pump genes of A. baumannii. In addition, the bacteria did not acquire stable drug-resistant ability. Cec4 at 1.024 mg/mL did not affect the proliferation of HeLa and HepG2 cells, and Cec4 at 45 mg/kg had little effect on the mortality of Caenorhabditis elegans, even the liver and kidney tissues of mouse. Most importantly, Cec4 could effectively improve the survival rates and reduce the bacterial load of various tissues in the mouse model of infection. CONCLUSION: In conclusion, Cec4 can damage the cell membrane of bacteria, and the bacteria is not easy to produce resistance to Cec4. Besides, Cec4 has good potential for the treatment of multidrug-resistant A. baumannii infections.
format Online
Article
Text
id pubmed-10069437
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher Dove
record_format MEDLINE/PubMed
spelling pubmed-100694372023-04-04 Antimicrobial Peptide Cec4 Eradicates Multidrug-Resistant Acinetobacter baumannii in vitro and in vivo Peng, Jian Wang, Yue Wu, Zhaoyin Mao, Chengju Li, Lu Cao, Huijun Qiu, Zhilang Guo, Guo Liang, Guiyou Shen, Feng Drug Des Devel Ther Original Research INTRODUCTION: Acinetobacter baumannii has become a major difficulty in the treatment of bacteria-associated infection. The previously reported antimicrobial peptide Cec4 exhibited good and stable activity against A. baumannii in vitro, but the mechanisms and effects in vivo are elusive. METHODS: The effects of Cec4 on bacterial membrane permeability, membrane potential and bacterial reactive oxygen species were measured. The cell membrane localization of antimicrobial peptides was studied by fluorescence labelling. The ability of bacteria to develop resistance to antimicrobial peptides was studied by continuous induction, and transcriptome difference was analysed. The in vivo toxicity of Cec4 against nematodes and mice was studied, and the in vivo therapeutic potential of Cec4 against A. baumannii was assessed. RESULTS: Cec4 effectively cleared multidrug-resistant A. baumannii by altering bacterial cell membrane permeability, changing bacterial cell membrane polarity, and increasing bacterial intracellular reactive oxygen species. Cec4 affected the expression of the secretion system, outer membrane, and efflux pump genes of A. baumannii. In addition, the bacteria did not acquire stable drug-resistant ability. Cec4 at 1.024 mg/mL did not affect the proliferation of HeLa and HepG2 cells, and Cec4 at 45 mg/kg had little effect on the mortality of Caenorhabditis elegans, even the liver and kidney tissues of mouse. Most importantly, Cec4 could effectively improve the survival rates and reduce the bacterial load of various tissues in the mouse model of infection. CONCLUSION: In conclusion, Cec4 can damage the cell membrane of bacteria, and the bacteria is not easy to produce resistance to Cec4. Besides, Cec4 has good potential for the treatment of multidrug-resistant A. baumannii infections. Dove 2023-03-30 /pmc/articles/PMC10069437/ /pubmed/37020803 http://dx.doi.org/10.2147/DDDT.S405579 Text en © 2023 Peng et al. https://creativecommons.org/licenses/by-nc/3.0/This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/ (https://creativecommons.org/licenses/by-nc/3.0/) ). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
spellingShingle Original Research
Peng, Jian
Wang, Yue
Wu, Zhaoyin
Mao, Chengju
Li, Lu
Cao, Huijun
Qiu, Zhilang
Guo, Guo
Liang, Guiyou
Shen, Feng
Antimicrobial Peptide Cec4 Eradicates Multidrug-Resistant Acinetobacter baumannii in vitro and in vivo
title Antimicrobial Peptide Cec4 Eradicates Multidrug-Resistant Acinetobacter baumannii in vitro and in vivo
title_full Antimicrobial Peptide Cec4 Eradicates Multidrug-Resistant Acinetobacter baumannii in vitro and in vivo
title_fullStr Antimicrobial Peptide Cec4 Eradicates Multidrug-Resistant Acinetobacter baumannii in vitro and in vivo
title_full_unstemmed Antimicrobial Peptide Cec4 Eradicates Multidrug-Resistant Acinetobacter baumannii in vitro and in vivo
title_short Antimicrobial Peptide Cec4 Eradicates Multidrug-Resistant Acinetobacter baumannii in vitro and in vivo
title_sort antimicrobial peptide cec4 eradicates multidrug-resistant acinetobacter baumannii in vitro and in vivo
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10069437/
https://www.ncbi.nlm.nih.gov/pubmed/37020803
http://dx.doi.org/10.2147/DDDT.S405579
work_keys_str_mv AT pengjian antimicrobialpeptidecec4eradicatesmultidrugresistantacinetobacterbaumanniiinvitroandinvivo
AT wangyue antimicrobialpeptidecec4eradicatesmultidrugresistantacinetobacterbaumanniiinvitroandinvivo
AT wuzhaoyin antimicrobialpeptidecec4eradicatesmultidrugresistantacinetobacterbaumanniiinvitroandinvivo
AT maochengju antimicrobialpeptidecec4eradicatesmultidrugresistantacinetobacterbaumanniiinvitroandinvivo
AT lilu antimicrobialpeptidecec4eradicatesmultidrugresistantacinetobacterbaumanniiinvitroandinvivo
AT caohuijun antimicrobialpeptidecec4eradicatesmultidrugresistantacinetobacterbaumanniiinvitroandinvivo
AT qiuzhilang antimicrobialpeptidecec4eradicatesmultidrugresistantacinetobacterbaumanniiinvitroandinvivo
AT guoguo antimicrobialpeptidecec4eradicatesmultidrugresistantacinetobacterbaumanniiinvitroandinvivo
AT liangguiyou antimicrobialpeptidecec4eradicatesmultidrugresistantacinetobacterbaumanniiinvitroandinvivo
AT shenfeng antimicrobialpeptidecec4eradicatesmultidrugresistantacinetobacterbaumanniiinvitroandinvivo