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Fig. 4.3 Siderocalin-carboxymycobactin structures. Scn-carboxymycobactin (n = 5) tail-in con-
figuration ( left ) and tail-out configuration ( right ). Iron is represented by the orange sphere ; for
clarity iron bonds to chelating moieties are not shown
4.4 Scn Location and Contact with Mycobacteria
In many cases, the binding interactions between carboxymycobactin and Scn serve
to protect the host from mycobacterial infections in vivo. The observed defense is
always iron-dependent, [ 43 , 44 ] implying that Scn functions through the binding
interactions quantified in vitro to intercept ferric carboxymycobactin and inhibit
mycobacterial iron acquisition. However, the iron-withholding defense is penetra-
ble, and at least in some cases, mycobacteria have the upper hand in the struggle
for iron.
Scn provides significant defense against M. tuberculosis at the early infection
stage when the pathogen is extracellular. Depending on the location of the infec-
tion, different cell types provide protection against an infection by secreting Scn.
Alveolar epithelial cells secrete Scn into the alveolar space in response to early
mycobacterial infection [ 44 ]. Neutrophils secrete Scn and protect against M.
tuberculosis infections in whole blood alluding to at least one reason why success-
ful M. tuberculosis infections in humans have been correlated to a lower neutro-
phil count [ 43 ]. In mice, the Scn level in blood is elevated at least 10 fold in the
first two days after infection with Mycobacterium avium resulting in a 2-10 fold
decrease of bacteria in the blood compared to Scn-knockout mice [ 35 ]. When Scn
is able to interact directly with mycobacteria in the extracellular environment, it
effectively inhibits growth by limiting iron for the pathogen.
After the early stages of a mycobacterial infection, the pathogen moves inside
host cells by phagocytosis. Alveolar epithelial cells are infected by mycobacteria,
but the number of mycobacteria in alveolar epithelial cells is generally low due to
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