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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
immunology and microbiology
Two tiered biological containment strategy for Lactococcus lactis-based vaccine or immunotherapy vectors
Human Vaccines and Immunotherapeutics, Volume 10, No. 2, Year 2014
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Description
The concept of biological containment was developed as a strategy to prevent environmental dissemination of engineered live vaccine or drug delivery vehicles. A mutation in the gene encoding thymidylate synthase (thyA), a key enzyme in the pyrimidine biosynthetic pathway, has previously been shown to limit growth of L. lactis vectors under restrictive conditions. We hypothesized that further mutations in the pyrimidine biosynthetic pathway might enhance the stability and safety of live L. lactis vectors. We show that a double mutation in the genes encoding ThyA and CTP synthase (PyrG) in L. lactis confers double auxotrophy for both thymidine and cytidine. However, the combination of two mutations failed to enhance the biological containment phenotype of the engineered strain. In the absence of thymine/thymidine, the thyA mutant exhibited a strong bactericidal phenotype. However, creation of the double mutant caused the loss of this phenotype, though survival in the mouse GI tract was enhanced. The implications for biological containment of live L. lactis based delivery vectors are discussed. © 2014 Landes Bioscience.
Authors & Co-Authors
Hanin, Aurelie
Ireland, Cork
Apc Microbiome Ireland
Ireland, Cork
University College Cork
Culligan, Eamonn P.
Ireland, Cork
Apc Microbiome Ireland
Ireland, Cork
University College Cork
Casey, Pat G.
Ireland, Cork
Apc Microbiome Ireland
Ireland, Cork
University College Cork
Bahey-El-Din, Mohammed
Egypt, Alexandria
Faculty of Pharmacy
Hill, Colin
Ireland, Cork
Apc Microbiome Ireland
Ireland, Cork
University College Cork
Gahan, Cormac G.M.
Ireland, Cork
Apc Microbiome Ireland
Ireland, Cork
University College Cork
Statistics
Citations: 6
Authors: 6
Affiliations: 3
Identifiers
Doi:
10.4161/hv.26954
ISSN:
21645515
e-ISSN:
2164554X
Research Areas
Cancer
Genetics And Genomics