Defense Date


Document Type


Degree Name

Master of Science


Microbiology & Immunology

First Advisor

Dr. Todd Kitten

Second Advisor

Dr. Kimberly Jefferson

Third Advisor

Dr. Darrell Peterson


Manganese-deficient Streptococcus sanguinis mutants exhibit a dramatic decrease in virulence for infective endocarditis and in aerobic growth in manganese-limited media. Loss of activity of a manganese-dependent, oxygen-dependent ribonucleotide reductase (RNR) could explain the decrease in virulence. When the genes encoding this RNR are deleted, there is no growth of the mutant in aerobic broth culture or in an animal model. Testing the contribution of the aerobic RNR to the phenotype of a manganese transporter mutant, a heterologous class II RNR from Lactobacillus leichmannii called NrdJ that requires B12 rather than manganese as a cofactor was previously introduced into an RNR mutant of S. sanguinis. Aerobic growth was only partially restored. Currently, we sought to improve NrdJ-dependent growth by (i) amending the medium to increase cellular levels of B12; (ii) characterizing a spontaneous mutant of the NrdJ-complemented strain with improved aerobic growth; and (iii) altering this strain through further genetic manipulation.


© John Lee Smith

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Date of Submission


Available for download on Sunday, June 26, 2022