How do bacteria know they have had enough?

Haem is a molecule fundamental for all living organisms. In humans, haem confers the red colour to haemoglobin-containing cells that transport oxygen, while in bacteria it is used as a cofactor in a large number of proteins with essential biological functions that sustain growth and survival. Due to its importance, almost all organisms have the capacity to synthesize haem endogenously. Moreover, several bacterial pathogens also utilize specialized systems that "steal" haem from haemoglobin of the infected host. However, too much haem is toxic to cells and is thus fundamental to have a mechanism that inhibits haem synthesis when the external uptake is active. Such mechanism has just been revealed in Lígia Saraiva Lab and published today in Molecular Microbiology.

"We describe how the human pathogen Staphylococcus aureus deals with this conundrum. The protein-protein interaction that occurs between IsdG, one of two S. aureus haem monooxygenase enzymes that belong to the external haem uptake system, and ferrochelatase, the last enzyme of the S. aureus haem biosynthetic pathway, inhibits the endogenous formation of haem. This seems to be a general mechanism as IsdG homologues appear widespread in many pathogens, and we propose that this crosstalk reconciles their high haem requirements with the paradox that excess of haem is lethal," according to Lígia Saraiva, corresponding author.

More information:
Marco A.M. Videira et al. Staphylococcus aureus haem biosynthesis and acquisition pathways are linked through haem monooxygenase IsdG, Molecular Microbiology (2018). DOI: 10.1111/mmi.14060

Provided by Instituto de Tecnologia Química e Biológica