Heme uptake and porphyrin homeostasis in Gram-negative bacteria:
from function to structure and vice-versa.

Philippe Delepelaire (CNRS Research Director), Marc Uzan (CNRS Research Director),
Annick Paquelin (CNRS technician), Yvette NTSOGO (Post-doc labex Dynamo)

Iron is an essential component for most living organisms. Heme (iron protoporphyrin IX) is the major iron source for commensal and pathogenic bacteria that develop inside mammals as heme contained in hemoglobin represents more than 50% of all body iron. Bacteria have developed many systems to take up this molecule, that they most often use as an iron source (requiring heme iron extraction), or as a heme source.

To do so, Gram-negative bacteria use the so-called TonB-Dependent Transporters (TBDT’s), found in their outer membrane, together with the TonB complex from the cytoplasmic membrane. Heme specific TBDT’s bind heme (they might also bind hemoproteins) and internalize it into the periplasm. This is an energy-requiring process powered by the proton motive force (pmf) and recruiting of the TonB complex.


Spatial (top) and genetic (bottom) organizations of the Hxu (left) and Has (right) heme acquisition systems.
The TonB dependent receptors are HxuC and HasR, the hemophores HxuA and HasA, TonB/HasB-ExbB-ExbD energize heme (red rectangle) transport across HxuC and HasR, Hxua is secreted through HxuB (Two-Partner-Secretion, TPS), HasA is secreted through the Type I Secretion System (TISS) HasD-HasE-TolC.
HasI and HasS are respectively specific sigma and anti-sigma factors involved in regulation of has genes expression, besides the general regulation by Fur.

Our aim is to understand how these macromolecular assemblages work, from the molecular level to their integration into the bacterial cell physiology. Two models are studied, Has (heme acquisition system) from Serratia marcescens and Hxu (Hemopexin utilization) from Haemophilus influenzae. To this end we use molecular genetics, biochemistry and we collaborate with structural biologists and biophysicists.


Left: Structure of the hemophore-heme-receptor complex.
Right: Structure of the HxuA protein alone (left) and in complex with the N-terminal domain of hemopexin (right).

Related publications:
  • S. Krieg, F. Huché, K.Diederichs, N. Izadi-Pruneyre, A. Lecroisey, C Wandersman, P. Delepelaire and W. Welte Heme uptake across the outer membrane as revealed by crystal structures of the receptor-hemophore complex. Proc Natl Acad Sci U S A. 106: 1045-1050.(2009)(Pubmed)
  • S. Zambolin, B. Clantin, M. Chami, S. Hoos, A. Haouz,V. Villeret and P. Delepelaire Structural basis for haem piracy from host haemopexin by Haemophilus influenzae. Nat Commun. 7:11590.(2016) (Pubmed)

Last update: 17/02/23

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