Abstract
About 70% of all antibiotics produced in the world are used in the farm animal industry. The massive usage of antibiotics during farm animal production has caused rapid development of antibiotic resistance in bacteria, which poses a serious risk to human and livestock health when treating bacterial infections. Protegrin-1 (PG-1) is a potent antimicrobial peptide (AMP). It was initially identified in pig leukocytes with a broad-spectrum antibacterial and antiviral activity, and a low rate of inducing bacterial resistance. To develop a genetic approach for reducing the use of antibiotics in farm animal production, we produced transgenic mice carrying a bovine tracheal AMP gene promoter-controlled PG-1 transgene. The PG-1 transgene was specifically expressed in the respiratory tract of transgenic mice upon induction by bacterial infection. These PG-1 transgenic mice exhibited enhanced resistance to nasal bacterial infection as the transgenic mice showed a higher survival rate (79.17% VS. 34.78%), lower bacterial load and milder histological severity than their wild-type control littermates. The improved resistance to bacterial infection in the PG-1 transgenic mice could be resulted from the direct bacteria-killing activities of PG-1, and the immunomodulatory effects of PG-1 via stimulating interleukin 1 beta secretion. The present study provides a promising genetic strategy to prevent airway bacterial infections in farm animals by bacteria-inducible tissue-specific expression of PG-1 transgene. This approach may also be helpful for decreasing the possibility of inducing bacterial resistance during farm animal production.
Highlights
About 70% of all antibiotics produced in the world are used in the farm animal industry
A pTAP-PG-1 plasmid harboring a piggyBac transposon that carries a bacteria-inducible tracheal epithelial cell-specific bovine tracheal antimicrobial peptide (TAP) promoter-driven PG-1 gene was constructed (Fig. 1A). This plasmid contains a cytomegalovirus (CMV) promoter-controlled fusion selectable marker gene, which was composed of the neomycin (Neo) gene and an enhanced green fluorescence protein (EGFP) gene (Fig. 1A)
The pTAP-PG-1 plasmid was co-injected with the piggyBac transposase expression plasmid pmPB24 into the pronuclei of mouse zygotes (C57BL/6 strain)
Summary
About 70% of all antibiotics produced in the world are used in the farm animal industry. To develop a genetic approach for reducing the use of antibiotics in farm animal production, we produced transgenic mice carrying a bovine tracheal AMP gene promotercontrolled PG-1 transgene. The present study provides a promising genetic strategy to prevent airway bacterial infections in farm animals by bacteria-inducible tissue-specific expression of PG-1 transgene. Using a respiratory tract-specific and bacteriuminducible promoter to drive AMP transgene expression could be an effective approach to improve resistance to infectious respiratory diseases in farm animals, while reducing the likelihood of inducing bacterial resistance. We generated transgenic mice that carry a PG-1 transgene controlled by the bovine tracheal antimicrobial peptide (TAP) gene promoter These transgenic mice were used as models to test whether the bacteria-inducible and respiratory tract-specific expression of PG-1 transgene in animals can increase the animals’ resistance to airway bacterial infection. These transgenic mice exhibited enhanced resistance to nasal challenge of Actinobacillus pleuropneumoniae (A.pp) bacterium, which is the causative pathogen of the highly prevalent porcine pleuropneumonia d isease[23]
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