Iron is a critical co-factor 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
bacteremia available
iron from
heme and non-
heme proteins potentially increases. In
iron-depleted medium pneumococcal strain TIGR4 showed reduced growth, however, addition of several physiological
iron sources restored growth. Gene expression of selected known and putative pneumococcal
virulence factors was analyzed by quantitative RT-PCR in response to
iron sources in vitro and during colonization,
pneumonia, and
bacteremia in a mouse model. Change in
mRNA levels relative to transcription in
iron-depleted medium was reported. In presence of
iron sources, transcription of cps4A, zmpA, pavA,
hemolysin and a putative exfoliative toxin was significantly increased, but nanB was suppressed.
Hemoglobin at physiological concentration repressed ply and pspA expression.
Ferritin, an
acute phase protein, increased expression of an
iron ABC transporter and repressed expression of a bacterial non-
heme iron-containing
ferritin. Transcription of cps4A, nanB,
hemolysin, and a putative exfoliative toxin were significantly up-regulated during
pneumonia and
bacteremia, while
mRNA of pavA and non-
heme ferritin were expressed at higher levels during
pneumonia and carriage. An
iron ABC transporter was most up-regulated during
bacteremia, while pspA and ply were expressed only in
pneumonia. Transcription of zmpA was elevated during both
pneumonia and
bacteremia. 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.