Porphyrin-mediated cell surface heme capture from hemoglobin by Porphyromonas gingivalis.
The porphyrin requirements for growth recovery of Porphyromonas gingivalis in heme-depleted cultures are investigated. In addition to physiologically relevant sources of heme, growth recovery is stimulated by a number of noniron porphyrins. These data demonstrate that, as for Haemophilus influenzae, reliance on captured iron and on exogenous porphyrin is manifest as an absolute growth requirement for heme. A number of outer membrane proteins including some gingipains contain the hemoglobin receptor (HA2) domain. In cell surface extracts, polypeptides derived from HA2-containing proteins predominated in hemoglobin binding. The in vitro porphyrin-binding properties of a recombinant HA2 domain were investigated and found to be iron independent. Porphyrins that differ from protoporphyrin IX in only the vinyl aspect of the tetrapyrrole ring show comparable effects in competing with hemoglobin for HA2 and facilitate growth recovery. For some porphyrins which differ from protoporphyrin IX at both propionic acid side chains, the modification is detrimental in both these assays. Correlations of porphyrin competition and growth recovery imply that the HA2 domain acts as a high-affinity hemophore at the cell surface to capture porphyrin from hemoglobin. While some proteins involved with heme capture bind directly to the iron center, the HA2 domain of P. gingivalis recognizes heme by a mechanism that is solely porphyrin mediated.
Paramaesvaran
Mayuri
M
Institute of Dental Research, Centre for Oral Health, Westmead Hospital, Wentworthville, Sydney NSW 2145, Australia.
Nguyen
Ky-Anh
KA
Caldon
Elizabeth
E
McDonald
James A
JA
Najdi
Sherean
S
Gonzaga
Graciel
G
Langley
David B
DB
DeCarlo
Arthur
A
Crossley
Maxwell J
MJ
Hunter
Neil
N
Collyer
Charles A
CA
D018829:Adhesins, Bacterial / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism; D003470:Culture Media; D003546:Cysteine Endopeptidases / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism; D003905:Deuteroporphyrins; D000080867:Gingipain Cysteine Endopeptidases; D006388:Hemagglutinins / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism; D006418:Heme / Q000378:metabolism*; D006454:Hemoglobins / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism; D011166:Porphyrins / Q000378:metabolism / Q000502:physiology*; D016966:Porphyromonas gingivalis / Q000254:growth & development / Q000378:metabolism*; D011524:Protoporphyrins; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism
D018829:Adhesins, Bacterial; D003470:Culture Media; D003905:Deuteroporphyrins; D000080867:Gingipain Cysteine Endopeptidases; D006388:Hemagglutinins; D006454:Hemoglobins; D010455:Peptides; D011166:Porphyrins; D011524:Protoporphyrins; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; D006418:Heme; C028839:deuteroporphyrin-IX; D003546:Cysteine Endopeptidases