It has been known for some time that Haemophilus influenzae has an absolute growth requirement for a porphyrin or haem source, but new research just published in Microbiology reveals that haem utilization by this pathogen is even more complex than previously supposed.

The only known niche exploited by H. influenzae are humans, where the microorganism causes a range of infections including meningitis and pneumonia. As H. influenzae lacks all of the biosynthetic enzymes that are required to produce the porphyrin ring, a precursor of haem, the microorganism has evolved a complex array of uptake mechanisms to acquire this essential nutrient from its host environment. Previous work has shown that H. influenzae can use these acquisition systems to access a variety of haem sources including haemoglobin, the haemoglobin–haptoglobin and haem–haemopexdin complexes, and free haem itself. Stull and colleagues add a new layer of complexity to this essential process by describing an H. influenzae protein, called haem-utilization protein (Hup), which is central to the microorganism's exploitation of multiple haem sources.

To identify new proteins used by H. influenzae to acquire haem, the authors used a haemoglobin affinity method by which a 100-kDa protein was isolated. N-terminal amino acid sequencing of this protein allowed identification of the corresponding gene, which was used to create a deletion mutant of H. influenzae. As anticipated, characterization of the Δhup mutant strain revealed a reduced capacity to utilize haemoglobin in vitro. Furthermore, the mutant strain also demonstrated a reduced capacity to exploit haem, haem–haemopexin, haem–albumin and haemoglobin–haptoglobin, indicating a central role for the protein in haem acquisition by H. influenzae. The authors also investigated whether Hup contributes to the virulence of H. influenzae in an infant rat model of invasive disease and showed that, at least in this model, expression of Hup was not required for pathogenicity. The authors suggest that this finding could reflect the fact that bacterial haem-uptake mechanisms may be specific to the haem sources from the host natural species — it is not known whether H. influenzae can exploit sources of haem from the rat.

So, although the in vivo relevance of Hup remains to be established, the data presented in this study clearly suggests a central role for this protein in haem acquisition by H. influenzae. The authors hypothesize that Hup may be used in the extraction and internalization of haem from various haem-binding proteins in the host environment. Future work will investigate this hypothesis and clarify the role of Hup in the pathogenic mechanisms of H. influenzae disease.