Muriel Herrington, PhD

Education

PhD (McMaster)

Research interests

(Please note that I am no longer accepting graduate students)

Folate metabolism in Escherichia coli

Antifolate drugs such as methotrexate and trimethoprim have a long history of successfully combatting diseases such as cancers, arthritis, urinary tract infections, toxoplasmosis and other infections. In humans, folate deficiency contributes to problems in neural tube development in the fetus resulting in spinal cord defects in newborns, and is implicated in cardiovascular disease. Folates are required for the normal growth and proliferation of all cells and when they are not available cells ultimately die. A better understanding of the biosynthesis of folates and the consequences of disturbing folate biosynthesis in microorganisms will contribute to our understanding of this important biochemical pathway as well as assist us to devise appropriate drug regimes and to design new drugs. Non-pathogenic laboratory strains of the intestinal bacteria Escherichia coli are an excellent model system for the study of biosynthesis of folates. First, like many pathogens, E. coli synthesizes folates from simpler compounds and thus permits us to study the entire biosynthetic pathway. Secondly, there is a wealth of genetic, biochemical and molecular data available for E. coli, permitting rapid dissection of novel phenotypes.

E. coli mutants that lack dihydrofolate reductase grow on minimal media containing combinations of the folate end products but do not grow on media supplemented with other combinations. We have isolated derivatives of these mutants that have different growth requirements and have identified some of the genes involved. We are currently working with two genes that change the phenotype of the mutant strain when expressed from a plasmid. The first codes for a presumptive transcription factor involved in stress responses that lead to biofilm formation. The other is a gene of unknown function. This project will allow us to identify and characterize genes that regulate the flow of different folate cofactors to the various biochemical pathways and that control the biosynthesis of the folate cofactors.

Genetics and Human Welfare
Mechanisms of Protein Synthesis

Chirwa NT, Herrington MB. 2004. Role of MetR and PurR in the activation of glyA by CsgD in Escherichia coli K-12. Can J Microbiol. 50(9): 683-90.

Chirwa NT, Herrington MB. 2003. CsgD, a regulator of curli and cellulose synthesis, also regulates serine hydroxymethyltransferase synthesis in Escherichia coli K-12. Microbiology. 149(Pt 2): 525-35.

Herrington MB, Chirwa NT. 1999. Growth properties of a folA null mutant of Escherichia coli K12. Can J Microbiol. 45(3): 191-200.

Herrington MB. 1994. Measurement of the uptake of radioactive para-aminobenzoic acid monitors folate biosynthesis in Escherichia coli K-12. Anal Biochem. 216(2): 427-30.

Basso J, Herrington MB. 1994. Changes in translational accuracy of Escherichia coli when folate metabolism is perturbed. Microbios. 77(313): 231-7.

Tiganos E, Herrington MB. 1993. Kasugamycin inhibition of nonsense suppression by thymine-requiring strains of Escherichia coli K12. Can J Microbiol. 39(4): 448-50.