Drug resistant bacteria have developed a preference for haem iron.

The bacterium Staphylococcus aureus is (in)famous for its ability to pick up resistance genes, resulting in the dreaded MDRSA (multi-drug resistant Staphylococcus aureus) strains. Researchers at the University of Chicago, US, have now exposed this microbe as a ruthless thief: it steals iron from its hosts, complete with the haem ligand.

Cutting off iron supplies might be a way to treat bacterial infections, but requires precise knowledge of where the bacteria get their iron. Traditional bacterial metabolism studies offer just one nutrient and monitor its use. To find out which nutrient source bacteria prefer, Olaf Schneewind's group used isotopic labelling studies. Iron comes in four varieties, with 54, 56, 57 or 58 nucleons. ⁵⁶Fe is most abundant, at over 91 per cent, and is ruled out from isotopic tracer studies. The other three are sufficiently rare to give useful measurements. Moreover, metabolism does not seem to favour any one isotope.

Most of the iron in the human body is found in the oxygen carriers haemoglobin and myglobin, while only very little is bound to the iron carrier protein transferrin. Thus, the researchers started from the hypothesis that human pathogens might have evolved a preference for haem iron. They supplied bacterial cultures with a choice of ⁵⁴Fe hemin and ⁵⁷Fe transferrin to study the uptake. The answers were clearcut but more complicated than expected. S. aureus does prefer haem iron over transferrin-bound iron, but the ratio depends on the growth phase. Moreover, iron from different sources was directed to different destinations in the cell. Haem iron was more likely to end up in membrane proteins, perhaps directly incorporated into redox enzymes, complete with the ligand.

Using the isotope analysis in conjunction with the genome data, the researchers assigned the different kinds of iron uptake to specific genes. Knocking out the haem uptake gene made the bacteria significantly less lethal to the worm Caenorhabditis elegans. Thus, the bacterial haem import could be a promising drug target, which might one day help to eradicate those hospital bugs.

Michael Gross