In:
Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Vol. 51, No. 2 ( 2007-02), p. 724-731
Abstract:
To
evaluate the potentiality of applying gene therapy to bacterial infections, especially for preventing infection in high-risk patients,
we investigated protection of mice from challenge with lethal Escherichia coli infection by adeno-associated virus serotype
2 (AAV2)-mediated gene transfer of a chimeric BPI 23 -Fcγ1 gene, which consisted of human
bactericidal/permeability-increasing protein (BPI) gene encoding the functional N terminus (amino acid residues 1 to 199) of human BPI and
an Fcγ1 gene encoding the Fc segment of human immunoglobulin G1. Here we show that the target protein that was expressed and
secreted into the serum of the gene-transferred mice demonstrated the activity of a neutralizing endotoxin, killing E. coli and
mediating opsonization. After lethal E. coli infection, the
count of bacteria and the levels of endotoxin and proinflammatory cytokines in the gene-transferred mice were decreased. The survival
rate of BPI 23 -Fcγ1 gene-transferred mice markedly
increased, especially in conjunction with antibiotics. Our data suggest that AAV2-mediated chimeric BPI 23 -Fcγ1 gene delivery
could potentially be used clinically for the protection and treatment of infection with gram-negative bacteria in high-risk
individuals.
Type of Medium:
Online Resource
ISSN:
0066-4804
,
1098-6596
DOI:
10.1128/AAC.00360-06
Language:
English
Publisher:
American Society for Microbiology
Publication Date:
2007
detail.hit.zdb_id:
1496156-8
SSG:
12
SSG:
15,3
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