Mycobacterial Iron Acquisition Mechanisms - Iron Acquisition by the Genus Mycobacterium - page 47

markedly sensitive to oxidative stress agents, demonstrating the need for iron stor-
age proteins in prevention of iron induced damage.
Individual knockout of M. tuberculosis bfrA an bfrB revealed that ferritin may
be essential for the maintenance of iron homeostasis [ 49 ]. M. tuberculosis lacking
ferritin suffered from iron induced toxicity, was unable to persist in mice and was
highly susceptible to killing by antibiotics. The iron storage proteins are essential
components of the iron acquisition process.
3.6 Low Affinity and Reductive Mycobacterial Iron
Acquisition
The saprophytic M. smegmatis exhibits low affinity iron capture from sources like
ferric citrate if present at elevated levels of iron [ 50 ]. The Msp porins of M. smeg-
matis are likely responsible for low affinity uptake because ferric-exochelin, the
siderophore of saprophytes, is acquired by a porin independent process involving
the fxuA - D genes. At high iron concentrations, the requirement for iron may be met
by low affinity uptake through porins. When the iron level falls or the number of
porins is lessened, M. smegmatis derepresses production of siderophores for high
affinity iron gathering. Where in the terrestrial environment a saprophyte would find
elevated iron is uncertain. It also seems unlikely that a strict pathogen like M. tuber-
culosis , which moves from the iron restricted condition of a human host to another
susceptible human, would encounter iron replete circumstances. Similarly, an
opportunistic mycobacterium causing an infection would face host iron withholding.
It is generally assumed that siderophores are deferrated internally by reduction
of the metal; however, bacterial cell surface reductases may be required to ren-
der iron to its soluble state for transport in some bacteria. Microorganisms like
Streptococcus mutans which does not produce siderophores likely require surface
reduction of iron prior to transport [ 51 ]. A novel extracellular ferric reductase was
discovered in Mycobacterium paratuberculosis capable of scavenging iron from
ferric-transferrin, ferritin, and ferric citrate [ 52 ]. Reduction of iron at the cell sur-
face is an alternative to iron capture by high affinity siderophores and may be a
major route in a few mycobacteria.
3.7 Iron and Continuous Growth of M. smegmatis
in a Teflon Chemostat: Biofilm Formation
Continuous cultivation of M. smegmatis was accomplished in a chemostat con-
structed of Teflon which overcomes the problem of metal leaching from glass and
stainless steel components [ 52 , 53 ]. There are few reports of continuous growth
of mycobacteria [ 54 ]. Unpublished studies [B. R. Byers and J. E. L. Arceneaux]
using a defined medium supplemented with high purity metals found that