Burkholderia cenocepacia utilizes ferritin as an iron source

Abstract

Burkholderia cenocepacia is a member of the Burkholderia cepacia complex, a group of genetically similar species that inhabit a number of environmental niches, including the lungs of patients with cystic fibrosis (CF). To colonize the lung, this bacterium requires a source of iron to satisfy its nutritional requirements for this important metal. Because of the high potential for damage in lung tissue resulting from oxygen–iron interactions, this metal is sequestered by a number of mechanisms that render it potentially unavailable to invading micro-organisms. Such mechanisms include the intracellular and extracellular presence of the iron-binding protein ferritin. Ferritin has a highly stable macromolecular structure and may contain up to 4500 iron atoms per molecule. To date, there has been no known report of a pathogenic bacterial species that directly utilizes iron sequestered by this macromolecule. To examine the ability of ferritin to support growth of B. cenocepacia J2315, iron-deficient media were supplemented with different concentrations of ferritin and the growth kinetics characterized over a 40 h period. The results indicated that B. cenocepacia J2315 utilizes iron bound by ferritin. Further studies examining the mechanisms of iron uptake from ferritin indicated that iron utilization results from a proteolytic degradation of this otherwise stable macromolecular structure. Since it is known that the ferritin concentration is significantly higher in the CF lung than in healthy lungs, this novel iron-acquisition mechanism may contribute to infection by B. cenocepacia in people with CF.

Iron acquisition in the cystic fibrosis lung and potential for novel therapeutic strategies

“…Burkholderia cenocepacia is also capable of exploiting the ferritin iron source in the CF lung by protease cleavage (Whitby et al, 2006). Our studies have shown that Burkholderia cenocepacia, in addition to ferritin, also has the ability to utilize lactoferrin and transferrin when siderophore production is unavailable (Tyrrell et al, 2015).…”

Sequestration and Scavenging of Iron in Infection

“…Ferritin is thought to be degraded by the host cell to meet its own iron needs; Neisseria is able to access the released iron as well (59). In contrast, in Burkholderia cenocepacia, an opportunistic pathogen of cystic fibrosis patients, ferritin degradation and subsequent iron release appear to be directly mediated by a secreted or surface-bound serine protease (60). Ferritin levels are known to be higher in the lungs of people with cystic fibrosis relative to healthy individuals, suggesting a direct link to the pathogenesis of this organism.…”

“…However, as noted above, certain pathogens are able to circumvent these decreases in available iron by utilizing ferritin as an iron source. Therefore, the increased ferritin in macrophages may ultimately be beneficial to a pathogen, such as B. cenocepacia, that can survive in a macrophage and utilize ferritin (60,108).…”

Transcriptional Profile of Haemophilus influenzae : Effects of Iron and Heme

“…Preliminary data indicate that HI1369 has a role in heme acquisition (data not shown). In other bacterial species, proteases play a direct role in the acquisition of iron and heme from various sources (12,21,24,28). The FeHm regulon contains genes with no known role in iron/heme uptake.…”