Silencing and reactivation of urease in Yersinia pestis is determined by one G residue at a specific position in the ureD gene

Yersinia pestis, the plague agent, is a naturally nonureolytic microorganis m, while all other Yersinia species display a potent urease activity. In th is report we demonstrate that Y. pestis harbors a complete urease locus com posed of three structural (ureABC) and four accessory (ureEFGD) genes. Abse nce of ureolytic activity is due to the presence of one additional G residu e in a poly(G) stretch, which introduces a premature stop codon in ureD. Th e presence of the same additional G in eight other Y. pestis isolates indic ates that this mutation is species specific. Spontaneous excision of the ex tra G occurs at a frequency of 10(-4) to 10(-5) and restores a ureolytic ph enotype to Y. pestis. The virulence of two independent ureolytic clones of Y. pestis injected either intravenously, subcutaneously, or intragastricall y did not differ from that of the parental strain in the mouse infection mo del. Coinfection experiments with an equal number of ureolytic and nonureol ytic bacteria did not evidence any difference in the ability of the two var iants to multiply in vivo and to cause a lethal infection. Altogether our r esults demonstrate that variation of one extra G residue in ureD determines the ureolytic activity of Y. pestis but does not affect its virulence for mice or its ability to multiply and disseminate.