Many pathogenic organisms use class Ib (NrdE-NrdF) and class III (NrdD-NrdG) ribonucleotide reductases (RNRs) to convert nucleotides to deoxynucleotides under aerobic and anaerobic conditions, repectively. Recently class Ib RNRs were established to use a dimanganese-tyrosyl radical cofactor whose assembly requires an unusual flavodoxin. These RNRs can also self-assemble an active diferric-tyrosyl radical cofactor. Our labs now report in vitro biochemical studies on S. sanguinis RNRs, in vivo biological studies on wt and deletion strains of S. sanguinis, and studies in a rabbit model for infective endocarditis caused by S. sanguinis. Together these studies establish the essentiality of the Mn-dependent RNR for virulence. They may also provide an explanation for a previous report that a Mn transporter is necessary for virulence and oxygen tolerance in S. sanguinis.

Role of dimanganese-tyrosyl radical ribonucleotide reductase in the virulence of Streptococcus sanguinis

247th National Meeting (2014)

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