| Pasteurella multocida causes a variety of diseases in animals and humans. Despite its long and rich history, a basic understanding of how and when specific biochemical and metabolic pathways are utilized by the organism during pathogenesis remains elusive. One of the most critical and limited elements required by bacteria upon entry into a host is iron. Therefore, successful pathogens must possess an effective system for acquiring iron whilst in a range of environmental conditions. Since P. multocida is a free-living organism that can also infect a variety of hosts, it likely utilizes distinct subsets of genes to acquire iron from different biological sources. It should be possible to identify these subsets of genes based on their transcriptional activity in response to defined iron sources. DNA microarrays representing all of the 2014 genes identified in P. multocida were utilized to monitor global transcriptional changes in response to low iron conditions, nutrient limitation, and defined sources of iron. Genes involved in energy metabolism and electron transport generally decreased 2.1 to 6-fold while those used for iron binding and transport increased 2.1 to 7.7-fold in expression in P. multocida during the first two hours of growth in iron-limiting conditions as compared with controls. Notably, 27% of the genes significantly altered in expression had no known function. A large number (n = 439) of genes including those involved in energy metabolism, transport, protein synthesis, and binding were expressed at higher levels in rich medium than in minimal medium, suggesting that upon exposure to a rich environment, P. multocida immediately begins to "turn on" many energy-intensive biosynthetic pathways or conversely turn these genes "off" when exposed to a nutrient deficient environment. Genes with increased expression in minimal medium ( n = 230) included those encoding amino acid biosynthesis and transport systems, outer membrane proteins, and heat shock proteins. On average, 12% of P. multocida genes were differentially expressed when cells were grown in the presence of hemoglobin, transferrin, ferritin, or ferric citrate. A majority of these genes encoded P. multocida proteins that were involved in either transport and binding or were annotated as hypothetical proteins, however, only two genes were significantly altered in expression for all of the iron sources tested. |
