Heme Acquisition Mechanisms in Bacterial Pathogens

Bacterial pathogens require iron to support critical cellular processes, yet hosts limit iron availability by sequestering it within haem-containing proteins. To overcome this nutritional immunity, pathogens have evolved diverse haem acquisition strategies. Gram-positive bacteria often deploy cell-surface haem-binding proteins that extract haem from host haemoproteins and relay it through a series of membrane‐anchored transporters before cytoplasmic degradation by haem oxygenases. Gram-negative species rely on outer membrane TonB-dependent transporters to import haem into the periplasm, periplasmic binding proteins to shuttle it, and inner membrane ABC transporters to deliver it to the cytosol. Additional layers of regulation, sensing and subcellular organisation ensure that haem uptake is efficient yet non-toxic. Collectively, these mechanisms underpin the ability of pathogens such as Staphylococcus aureus, Pseudomonas aeruginosa and Stenotrophomonas maltophilia to proliferate within iron-restricted host environments and contribute to disease pathogenesis.

Research from Nature Portfolio

Dual RNA-seq analyses of Pseudomonas aeruginosa during acute murine pneumonia have revealed a coordinated upregulation of haem uptake genes alongside host iron-sequestration responses. The pathogen markedly increased expression of haem acquisition operons, including outer membrane haem receptors and associated TonB complexes, in parallel with virulence factors. Simultaneously, the host lung tissue mounted a robust inflammatory response characterised by induction of iron-binding proteins. This study provides a comprehensive in vivo picture of the molecular tug-of-war for iron and highlights potential targets for anti-infective strategies.

Heme Acquisition Mechanisms in Bacterial Pathogens publication trend

The graph below shows the total number of articles in heme acquisition mechanisms in bacterial pathogens across all publications each year (not limited to Nature Index journals).

Technical terms

Heme: iron-containing porphyrin cofactor central to bacterial iron uptake and host nutritional immunity.

Isd system: iron-regulated surface determinant pathway comprising cell-surface receptors and transporters that extract and import haem in Gram-positive bacteria.

Functional membrane microdomains (FMMs): specialised lipid–protein regions within bacterial membranes that organise transport complexes for nutrient acquisition.

TonB-dependent transporter: outer membrane protein in Gram-negative bacteria that imports haem using energy transduced by the TonB–ExbB–ExbD complex.

ABC transporter: ATP-binding cassette transporter that hydrolyses ATP to translocate haem or other substrates across the cytoplasmic membrane.

Catch bond: molecular bond whose lifetime increases under applied mechanical force, promoting stable interactions under stress.

References

1. Dual-seq transcriptomics reveals the battle for iron during Pseudomonas aeruginosa acute murine pneumonia. Scientific Reports (2016).
2. Functional membrane microdomains and the hydroxamate siderophore transporter ATPase FhuC govern Isd-dependent heme acquisition in Staphylococcus aureus. eLife (2023).
3. HemU and TonB1 contribute to hemin acquisition in Stenotrophomonas maltophilia. Frontiers in Cellular and Infection Microbiology (2024).
4. Nanoscale dynamical investigation of the hemoglobin complex with the bacterial protein IsdB: is their interaction stabilized by catch bonds?. Nanoscale (2024).