B-178. A Subset of Genes in Streptococcus pneumoniae Responds to the Type and Quantity of Iron Sources Available in Vivo

R. Gupta1, E. Swiatlo2;
1Univ. of Mississippi Med. Ctr., Jackson, MS, 2Va Med. Ctr., Jackson, MS.

Iron is a critical cofactor for several enzymes and is known to regulate gene expression in many pathogens. Streptococcus pneumoniae (pneumococcus) normally colonizes the upper respiratory mucosa, which is an iron restricted environment. In contrast, during systemic infection available iron potentially increases from higher levels of heme and non-heme proteins. Transcription of selected known and putative pneumococcal virulence factors was analyzed by quantitative RT-PCR in response to physiologically relevant iron sources in vitro, at the onset and development of carriage, pneumonia, and bacteremia in a mouse model following intranasal infection, and also during cerebrospinal fluid (CSF) exposure. Fold induction of mRNA levels relative to cells grown in iron-depleted medium were reported. Transcription of cps4A, nanB, hemolysin, and putative exfoliative toxin, were significantly up-regulated during pneumonia and bacteremia, while mRNAs of pavA and non heme ferritin (intracellular iron storage protein) were expressed at higher levels during pneumonia and carriage. At this time, an iron ABC transporter was most abundant in bacteremia, while pspA and ply were expressed only in pneumonia, whereas increased amounts of zmpA was found during pneumonia and bacteremia. Exposure to CSF, which is low in iron, increased expression of the iron ABC transporter, and either decreased or had no effects on the other genes. These findings suggest that a subset of virulence genes in pneumococci is differentially regulated in response to the quantity and form of iron sources available in a host.