GLOBAL TRANSCRIPTIONAL PROFILING OF THE HIGHLY ATTENUATED YERSINIA PESTIS NlpD MUTANT, REVEALS A DEFECT IN IRON METABOLISM AND DYSFUNCTION OF THE TWIN-ARGININE TRANSLOCATION SYSTEM

Yersinia pestis is the causative agent of plague which has caused millions of deaths in three world pandemics and is categorized by the CDC as a potential biological threat agent.

The ability of Y. pestis to respond to the host environment and to overcome its immune defense is attributed to the combined activity of multiple virulence pathways. Among these only few (e.g. the type 3 secretion system), have been found to be absolutely required for virulence in animal model systems.

We have identified the NlpD lipoprotein as a novel essential virulence factor of Y. pestis (Tidhar et al., 2009). The nlpD mutant was highly attenuated for virulence in the mouse models of plague. In an attempt to unravel the role of NlpD in Y. pestis pathogenesis we performed global transcriptional profiling of the nlpD mutant during logarithmic growth in culture media. Major changes in the expression of various transport systems were observed. About 30 percent of the genes that their expression was altered in the nlpD mutant are involved in iron transport systems and metabolic pathways that require iron such as aerobic respiration. Indeed, further analysis showed that the nlpD mutant has a growth defect in iron-deficient media.

The numerous phenotypes of the nlpD mutant including attenuation of virulence, iron acquisition defect and chain morphology were reminiscent of the phenotypes of twin-arginine translocation (TAT) system mutants in other Gram-negative bacteria. Indeed, using a reporter protein, we show that TAT system is non-functional in the Y. pestis nlpD mutant.

Further experiments are underway to elucidate the involvement of the TAT transport systems in the virulence phenotype of Y. pestis.