Iron and heme utilization inPorphyromonas gingivalis

Abstract

Porphyromonas gingivalis is a Gram-negative anaerobic bacterium associated with the initiation and progression of adult periodontal disease. Iron is utilized by this pathogen in the form of heme and has been shown to play an essential role in its growth and virulence. Recently, considerable attention has been given to the characterization of various secreted and surface-associated proteins of P. gingivalis and their contribution to virulence. In particular, the properties of proteins involved in the uptake of iron and heme have been extensively studied. Unlike other Gram-negative bacteria, P. gingivalis does not produce siderophores. Instead it employs specific outer membrane receptors, proteases (particularly gingipains), and lipoproteins to acquire iron/heme. In this review, we will focus on the diverse mechanisms of iron and heme acquisition in P. gingivalis. Specific proteins involved in iron and heme capture will be described. In addition, we will discuss new genes for iron/heme utilization identified by nucleotide sequencing of the P. gingivalis W83 genome. Putative iron- and heme-responsive gene regulation in P. gingivalis will be discussed. We will also examine the significance of heme/hemoglobin acquisition for the virulence of this pathogen.

The nucleoid-associated protein HUβ affects global gene expression in Porphyromonas gingivalis

“…The molecular mechanisms underlying iron uptake have been extensively studied (Olczak et al, 2005). Genes involved in iron acquisition include the hmuYRSTUV locus (PG1551-PG1556), which encodes a novel hybrid haemin-uptake system (Brunner et al, 2010;Lewis et al, 2006;Olczak et al, 2005Olczak et al, , 2008Simpson et al, 2000Simpson et al, , 2004Smalley et al, 2011); the hbp35 gene (PG0616), which encodes a haemin-binding protein that also exhibits thioredoxin activity (Hiratsuka et al, 2010;Shoji et al, 2010); the surface protein HusA (PG2227), which acts as a haemophore with very high affinity (Gao et al, 2010); the tlr (PG0644) iron transport locus Slakeski et al, 2000); the haemin-binding protein FetB (PG0669) and the surrounding genes in that locus; and PG0465, the ferric uptake regulator (fur) (Olczak et al, 2005). In addition, regulatory mechanisms controlling expression of iron acquisition genes have been identified, including the transcriptional activator encoded by PG1237, which has been shown to control expression of the hmu locus (Wu et al, 2009).…”

Quantitative proteomics of intracellular Porphyromonas gingivalis

“…Lacking siderophores, P. gingivalis employs specific outer membrane receptors, lipoproteins and proteases to acquire heme and iron [4,55]. Many of these systems were under-expressed, including: HmuR, a TonB-linked outer membrane receptor required for both hemoglobin and hemin utilization, and HmuY, a hemin binding protein in the same operon [51,52]; FetB (IhtB), a hemin binding lipoprotein that is located in an iron transport operon along with a TonB-linked outer membrane receptor, IhtA, [53] that was also under-expressed; and Kgp, that can degrade host iron-and heme-containing proteins, and possibly act as a hemophore, shuttling heme back to outer membrane receptors [55]. FeoB proteins [54] were not detected in these studies.…”

Gingipain-dependent interactions with the host are important for survival of Porphyromonas gingivalis

“…We and others have also demonstrated the ability of the gingipains to disrupt cell-cell and cell-matrix adhesion and induce apoptosis in several cell types (34,99,129,182,183). An involvement in hemoglobin binding and adsorption and heme accumulation further confirms their multiple contributions to bacterial survival, including oxidative stress resistance (3,107,114,152,191). …”

“…For example, there is evidence that the gingipains can modulate heme uptake/utilization which is vital for its survival [(151) and reviewed in (152)]. Fimbrial expression is also regulated by the gingipains (229).…”