Yersinia pestis is the causative agent of plague which has caused millions of deaths in three world pandemics and is categorized 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 systems. Among these systems, only few (e.g. the Type 3 secretion system), have been found to be absolutely required for virulence in animal model systems. We have recently identified the NlpD lipoprotein as a novel essential virulence factor of Y. pestis. A chromosomal deletion of the nlpD gene sequence resulted in a drastic reduction in virulence to an LD50 of at least 107 cfu for subcutaneous and airway routes of infection. In an attempt to understand the role of NlpD in Y. pestis pathogenesis we analyzed in the present study the in vitro global transcriptional profiling of the nlpD mutant using microarray. 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 mutant has a growth defect in iron-deficient media. As iron uptake in the host is crucial for bacterial virulence, our data suggests that the defect in iron uptake during infection might be a major factor leading to the attenuation of the nlpD mutant.
