Type

Journal Article

Authors

Cormac G M Gahan
Colin Hill
Mohammed Bahey-El-Din
Pat G. Casey
Eamonn P Culligan
Aurelie Hanin

Subjects

Microbiology

Topics
vaccines administration dosage gastrointestinal tract immunotherapy immunology enzymology animals genetics microbiology deficiency lactococcus lactis mice thymidylate synthase drug carriers growth development containment of biohazards carbon nitrogen ligases ctp synthetase adverse effects

Two-tiered biological containment strategy for Lactococcus lactis-based vaccine or immunotherapy vectors. (2013)

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.
Collections Ireland -> University College Cork -> PubMed

Full list of authors on original publication

Cormac G M Gahan, Colin Hill, Mohammed Bahey-El-Din, Pat G. Casey, Eamonn P Culligan, Aurelie Hanin

Experts in our system

1
Cormac G M Gahan
University College Cork
Total Publications: 109
 
2
Colin Hill
University College Cork
Total Publications: 351
 
3
Mohammed Bahey-El-Din
University College Cork
Total Publications: 8
 
4
Pat G. Casey
University College Cork
Total Publications: 40
 
5
Eamonn P Culligan
University College Cork
Total Publications: 13