Biodistribution of 89Zr-DFO-labeled avian pathogenic Escherichia coli outer membrane vesicles by PET imaging in chickens

ABSTRACT: Avian pathogenic Escherichia coli (APEC) is a serious systemic infectious disease in poultry infections, causing severe economic losses to the poultry industry. Previous studies have shown that secretion of virulence proteins was required for the pathogenicity of APEC through the secretion...

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Main Authors: Zhe Li, Lulu Niu, Lizhen Wang, Ting Mei, Wenbin Shang, Xi Cheng, Yuqing Li, Feng Xi, Xiangjun Song, Ying Shao, Yuping Xu, Jian Tu
Format: Article
Language:English
Published: Elsevier 2023-02-01
Series:Poultry Science
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S0032579122006587
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author Zhe Li
Lulu Niu
Lizhen Wang
Ting Mei
Wenbin Shang
Xi Cheng
Yuqing Li
Feng Xi
Xiangjun Song
Ying Shao
Yuping Xu
Jian Tu
author_facet Zhe Li
Lulu Niu
Lizhen Wang
Ting Mei
Wenbin Shang
Xi Cheng
Yuqing Li
Feng Xi
Xiangjun Song
Ying Shao
Yuping Xu
Jian Tu
author_sort Zhe Li
collection DOAJ
description ABSTRACT: Avian pathogenic Escherichia coli (APEC) is a serious systemic infectious disease in poultry infections, causing severe economic losses to the poultry industry. Previous studies have shown that secretion of virulence proteins was required for the pathogenicity of APEC through the secretion system. Outer membrane vesicles (OMVs) are a generalized secretion system of Gram-negative bacteria that play a key role in the long-distance delivery of virulence factors, but whether they are associated with the pathogenic mechanism of APEC has not been determined. In this study, OMVs were purified and characterized from AE17 (O2 serotype) by ultracentrifugation and density gradient centrifugation and their protein cargo was identified using liquid chromatography-tandem mass spectrometry (LC-MS/MS). In addition, 89Zr was labeled after chelating AE17 OMVs by DFO and positron emission tomography PET imaging was used to track 89Zr-DFO-OMVs in chickens and to pathologically analyze the distribution sites. This study showed that AE17 OMVs were membrane vesicles ranging in size from 20 to 200 nm and proteomic analysis revealed the presence of virulence proteins, including adhesion proteins OmpA, OmpC, OmpF, OmpX, FimH, FimC and FigE, and serum resistance proteins OmpT and MliC and immune response regulator proteins (FliC). In addition, in vivo PET imaging to track the biodistribution of AE17 OMVs showed that AE17 OMVs were taken up by the lung region and the gastrointestinal and renal regions but were not detected in other areas. Pathological analysis of the tissue sites where AE17 OMVs were ingested showed inflammatory responses and damage. These findings suggested that AE17 OMVs not only contained a group of virulence proteins associated with AE17 infection but can also deliver these virulence proteins over long distances and caused tissue inflammatory damage. Our study revealed a previously unidentified causative microbial signal in the pathogenesis of APEC that could aid in the development of vaccines and antibiotics effective against APEC.
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spelling doaj.art-d07b3097db6e4efc9a395aa8c61b4f8f2023-01-30T04:11:26ZengElsevierPoultry Science0032-57912023-02-011022102364Biodistribution of 89Zr-DFO-labeled avian pathogenic Escherichia coli outer membrane vesicles by PET imaging in chickensZhe Li0Lulu Niu1Lizhen Wang2Ting Mei3Wenbin Shang4Xi Cheng5Yuqing Li6Feng Xi7Xiangjun Song8Ying Shao9Yuping Xu10Jian Tu11Anhui Province Engineering Laboratory for Animal Food Quality and Bio-safety, College of Animal Science and Technology, Anhui Agricultural University, Hefei 230036, China; Anhui Province Key Laboratory of Veterinary Pathobiology and Disease Control, Anhui Agricultural University, Hefei 230036, ChinaAnhui Province Engineering Laboratory for Animal Food Quality and Bio-safety, College of Animal Science and Technology, Anhui Agricultural University, Hefei 230036, China; Anhui Province Key Laboratory of Veterinary Pathobiology and Disease Control, Anhui Agricultural University, Hefei 230036, ChinaAnhui Province Engineering Laboratory for Animal Food Quality and Bio-safety, College of Animal Science and Technology, Anhui Agricultural University, Hefei 230036, China; Anhui Province Key Laboratory of Veterinary Pathobiology and Disease Control, Anhui Agricultural University, Hefei 230036, China; NHC Key Laboratory of Nuclear Medicine, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine. Wuxi, Jiangsu 214063, ChinaAnhui Province Engineering Laboratory for Animal Food Quality and Bio-safety, College of Animal Science and Technology, Anhui Agricultural University, Hefei 230036, China; Anhui Province Key Laboratory of Veterinary Pathobiology and Disease Control, Anhui Agricultural University, Hefei 230036, ChinaAnhui Province Engineering Laboratory for Animal Food Quality and Bio-safety, College of Animal Science and Technology, Anhui Agricultural University, Hefei 230036, China; Anhui Province Key Laboratory of Veterinary Pathobiology and Disease Control, Anhui Agricultural University, Hefei 230036, ChinaAnhui Province Engineering Laboratory for Animal Food Quality and Bio-safety, College of Animal Science and Technology, Anhui Agricultural University, Hefei 230036, China; Anhui Province Key Laboratory of Veterinary Pathobiology and Disease Control, Anhui Agricultural University, Hefei 230036, ChinaAnhui Province Engineering Laboratory for Animal Food Quality and Bio-safety, College of Animal Science and Technology, Anhui Agricultural University, Hefei 230036, China; Anhui Province Key Laboratory of Veterinary Pathobiology and Disease Control, Anhui Agricultural University, Hefei 230036, ChinaAnhui Province Engineering Laboratory for Animal Food Quality and Bio-safety, College of Animal Science and Technology, Anhui Agricultural University, Hefei 230036, China; Anhui Province Key Laboratory of Veterinary Pathobiology and Disease Control, Anhui Agricultural University, Hefei 230036, ChinaAnhui Province Engineering Laboratory for Animal Food Quality and Bio-safety, College of Animal Science and Technology, Anhui Agricultural University, Hefei 230036, China; Anhui Province Key Laboratory of Veterinary Pathobiology and Disease Control, Anhui Agricultural University, Hefei 230036, ChinaAnhui Province Engineering Laboratory for Animal Food Quality and Bio-safety, College of Animal Science and Technology, Anhui Agricultural University, Hefei 230036, China; Anhui Province Key Laboratory of Veterinary Pathobiology and Disease Control, Anhui Agricultural University, Hefei 230036, ChinaNHC Key Laboratory of Nuclear Medicine, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine. Wuxi, Jiangsu 214063, ChinaAnhui Province Engineering Laboratory for Animal Food Quality and Bio-safety, College of Animal Science and Technology, Anhui Agricultural University, Hefei 230036, China; Anhui Province Key Laboratory of Veterinary Pathobiology and Disease Control, Anhui Agricultural University, Hefei 230036, China; Corresponding authors:ABSTRACT: Avian pathogenic Escherichia coli (APEC) is a serious systemic infectious disease in poultry infections, causing severe economic losses to the poultry industry. Previous studies have shown that secretion of virulence proteins was required for the pathogenicity of APEC through the secretion system. Outer membrane vesicles (OMVs) are a generalized secretion system of Gram-negative bacteria that play a key role in the long-distance delivery of virulence factors, but whether they are associated with the pathogenic mechanism of APEC has not been determined. In this study, OMVs were purified and characterized from AE17 (O2 serotype) by ultracentrifugation and density gradient centrifugation and their protein cargo was identified using liquid chromatography-tandem mass spectrometry (LC-MS/MS). In addition, 89Zr was labeled after chelating AE17 OMVs by DFO and positron emission tomography PET imaging was used to track 89Zr-DFO-OMVs in chickens and to pathologically analyze the distribution sites. This study showed that AE17 OMVs were membrane vesicles ranging in size from 20 to 200 nm and proteomic analysis revealed the presence of virulence proteins, including adhesion proteins OmpA, OmpC, OmpF, OmpX, FimH, FimC and FigE, and serum resistance proteins OmpT and MliC and immune response regulator proteins (FliC). In addition, in vivo PET imaging to track the biodistribution of AE17 OMVs showed that AE17 OMVs were taken up by the lung region and the gastrointestinal and renal regions but were not detected in other areas. Pathological analysis of the tissue sites where AE17 OMVs were ingested showed inflammatory responses and damage. These findings suggested that AE17 OMVs not only contained a group of virulence proteins associated with AE17 infection but can also deliver these virulence proteins over long distances and caused tissue inflammatory damage. Our study revealed a previously unidentified causative microbial signal in the pathogenesis of APEC that could aid in the development of vaccines and antibiotics effective against APEC.http://www.sciencedirect.com/science/article/pii/S0032579122006587avian pathogenic Escherichia coliouter membrane vesiclesproteomicsbiodistributionPETpathogenicity
spellingShingle Zhe Li
Lulu Niu
Lizhen Wang
Ting Mei
Wenbin Shang
Xi Cheng
Yuqing Li
Feng Xi
Xiangjun Song
Ying Shao
Yuping Xu
Jian Tu
Biodistribution of 89Zr-DFO-labeled avian pathogenic Escherichia coli outer membrane vesicles by PET imaging in chickens
Poultry Science
avian pathogenic Escherichia coli
outer membrane vesicles
proteomics
biodistribution
PET
pathogenicity
title Biodistribution of 89Zr-DFO-labeled avian pathogenic Escherichia coli outer membrane vesicles by PET imaging in chickens
title_full Biodistribution of 89Zr-DFO-labeled avian pathogenic Escherichia coli outer membrane vesicles by PET imaging in chickens
title_fullStr Biodistribution of 89Zr-DFO-labeled avian pathogenic Escherichia coli outer membrane vesicles by PET imaging in chickens
title_full_unstemmed Biodistribution of 89Zr-DFO-labeled avian pathogenic Escherichia coli outer membrane vesicles by PET imaging in chickens
title_short Biodistribution of 89Zr-DFO-labeled avian pathogenic Escherichia coli outer membrane vesicles by PET imaging in chickens
title_sort biodistribution of 89zr dfo labeled avian pathogenic escherichia coli outer membrane vesicles by pet imaging in chickens
topic avian pathogenic Escherichia coli
outer membrane vesicles
proteomics
biodistribution
PET
pathogenicity
url http://www.sciencedirect.com/science/article/pii/S0032579122006587
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