IRIS publication 271355834
Two-tiered biological containment strategy for Lactococcus lactis-based vaccine or immunotherapy vectors
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TY - - Reviews - Hanin, A,Culligan, EP,Casey, PG,Bahey-El-Din, M,Hill, C,Gahan, CGM - 2014 - February - Two-tiered biological containment strategy for Lactococcus lactis-based vaccine or immunotherapy vectors - Validated - 1 - Altmetric: 2 () - biological containment vaccine Lactococcus lactis thyA pyrG LISTERIA-MONOCYTOGENES ACID BACTERIA DELIVERY MUCOSAL TRANSFORMATION SYSTEM MICE LLO - 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. - 333 - 337 - 10.4161/hv.26954 DA - 2014/02 ER -
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@review{V271355834, = {Reviews}, = {Hanin, A and Culligan, EP and Casey, PG and Bahey-El-Din, M and Hill, C and Gahan, CGM }, = {2014}, = {February}, = {Two-tiered biological containment strategy for Lactococcus lactis-based vaccine or immunotherapy vectors}, = {Validated}, = {1}, = {Altmetric: 2 ()}, = {biological containment vaccine Lactococcus lactis thyA pyrG LISTERIA-MONOCYTOGENES ACID BACTERIA DELIVERY MUCOSAL TRANSFORMATION SYSTEM MICE LLO}, = {{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.}}, pages = {333--337}, = {10.4161/hv.26954}, source = {IRIS} }
Data as stored in IRIS
OTHER_PUB_TYPE | Reviews | ||
AUTHORS | Hanin, A,Culligan, EP,Casey, PG,Bahey-El-Din, M,Hill, C,Gahan, CGM | ||
YEAR | 2014 | ||
MONTH | February | ||
TITLE | Two-tiered biological containment strategy for Lactococcus lactis-based vaccine or immunotherapy vectors | ||
RESEARCHER_ROLE | |||
STATUS | Validated | ||
PEER_REVIEW | 1 | ||
TIMES_CITED | Altmetric: 2 () | ||
SEARCH_KEYWORD | biological containment vaccine Lactococcus lactis thyA pyrG LISTERIA-MONOCYTOGENES ACID BACTERIA DELIVERY MUCOSAL TRANSFORMATION SYSTEM MICE LLO | ||
REFERENCE | |||
ABSTRACT | 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. | ||
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START_PAGE | 333 | ||
END_PAGE | 337 | ||
DOI_LINK | 10.4161/hv.26954 | ||
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