Potential role for Streptococcus gordonii‐derived hydrogen peroxide in heme acquisition by Porphyromonas gingivalis

Abstract

Streptococcus gordonii, an accessory pathogen and early colonizer of plaque, co-aggregates with many oral species including Porphyromonas gingivalis. It causes α-hemolysis on blood agar, a process mediated by H O and thought to involve concomitant oxidation of hemoglobin (Hb). Porphyromonas gingivalis has a growth requirement for heme, which is acquired mainly from Hb. The paradigm for Hb heme acquisition involves the initial oxidation of oxyhemoglobin (oxyHb) to methemoglobin (metHb), followed by heme release and extraction through the actions of K-gingipain protease and/or the HmuY hemophore-like protein. The ability of S. gordonii to mediate Hb oxidation may potentially aid heme capture during co-aggregation with P. gingivalis. Hemoglobin derived from zones of S. gordonii α-hemolysis was found to be metHb. Generation of metHb from oxyHb by S. gordonii cells was inhibited by catalase, and correlated with levels of cellular H O production. Generation of metHb by S. gordonii occurred through the higher Hb oxidation state of ferrylhemoglobin. Heme complexation by the P. gingivalis HmuY was employed as a measure of the ease of heme capture from metHb. HmuY was able to extract iron(III)protoporphyrin IX from metHb derived from zones of S. gordonii α-hemolysis and from metHb generated by the action of S. gordonii cells on isolated oxyHb. The rate of HmuY-Fe(III)heme complex formation from S. gordonii-mediated metHb was greater than from an equivalent concentration of auto-oxidized metHb. It is concluded that S. gordonii may potentially aid heme acquisition by P. gingivalis by facilitating metHb formation in the presence of oxyHb.

Porphyromonas gingivalis adopts intricate and unique molecular mechanisms to survive and persist within the host: a critical update

“…S. gordonii helps P. gingivalis to acquire heam by promoting met-Hemoglobin formation in the presence of Oxy-Hemoglobin. The heme-binding protein receptor (Hmu-Y) of P. gingivalis' captures and extracts the Iron III-Protoporphyrin IX using the Met-Hemoglobin obtained from S. gordonii [89][90][91][92][93][94][95][96][97]. Hmu-Y along with its cognate outer-membrane receptor, HmuR, aid in the transportation of the heam molecule through the outer membrane of P. gingivalis.…”

“…This process of acquiring heam by P. gingivalis, also dependent upon the protein TonB, which helps to transduce energy for the passage of heam and other ligands into the periplasm. Furthermore, the Hmu-Y receptors help P. gingivalis to increase the extracellular polymeric substances (EPS) production that mediates cohesion among the microbial community and prevents injury from any external physical forces [90][91][92][93][94][95][96][97]. Under the ironlimited conditions, P. gingivalis expresses a haemophore-like protein, HusA, to mediate the uptake of essential porphyrin and support its survival within the host [92][93][94].…”

“…It is also known to upregulate P-21 Activated Kinase (PAK) and Rho-Associated-Kinase (ROCK) receptors that indirectly increase pro-inflammatory cytokines production in the host [90][91][92]. SerB dephosphorylates the serine residues of the Nuclear factor-kappa Beta (NF-κB) and inhibits CXCL8 induced IL8 production [15,[93][94][95][96][97][98][154][155][156][157][158]. Reduced IL8 levels impair the process of phagocytosis and allow P. gingivalis to use the epithelial cells as an autophagosome for its growth and survival [96,[149][150][151][152][153][154][155][156][157].…”

“…The PI3 K activation prevents phagocytosis, inhibits RhoA activation, and actin polymerization. The inhibition of TLR2-PI3 K pathway even impairs the process of phagocytosis by inhibiting the RhoA GTPase dependent actin polymerization [95][96][97][98][100][101][102][161][162][163]. The inhibition of LR2/ MyD88 signaling causes the death of infected neutrophils and blocks the process of phagocytosis in the host [29,96].…”

“…The activation of TLR2 is required for bacterial persistence and its deficiency has been linked with inhibition of alveolar bone resorption [ 161 ]. Apart from SerB, lipopolysaccharide (LPS), FimA fimbriae, Lipoteichoic acid of P. gingivalis modulate the immunoinflammatory response by inhibiting the production of antimicrobial molecules, complement system, and recruitment of leukocytes and favoring colonization of microorganisms in the periodontal tissues [ 95 – 98 , 100 , 151 , 155 , 160 – 162 ] P. gingivalis release of various antimicrobial peptides (βeta defensins 2), activate the coagulation cascade and the kallikrein/kinin cascade to increase the inflammation in the host [ 150 , 160 ].…”