As a response to infection, our immune cells release antimicrobial ‘bleach’ to destroy surrounding bacteria. Researchers at the de Duve Institute and the UCL, in collaboration with the University of Aix-Marseille, have now discovered how gram negative bacteria try to counter this oxidative assault. Their results were published today in the renowned journal Nature.
Bleach has been used for a long time as a disinfectant because of its oxidative properties. Also neutrophils in our body make use of this principle: they produce and release hypochlorous acid (HClO) to clear infections. Bacterial proteins become oxidized and lose their biological activity after exposure to HClO.
New research of the Belgian-French collaboration between the universities of Leuven and Aix-Marseille shows how bacteria try to cope with oxidative stress. In reaction to oxidants such as reactive oxygen species and chlorine, gram negative bacteria express two reducing proteins in the periplasmic space. This is no coincidence, since the bacterial envelope is particularly exposed to oxidative stress. The two proteins are called methionine sulfoxide reductases P and Q (MsrP/Q) and recuperate protein functionality in the periplasm by reducing methionine sulfoxide residues back to methionine. In this way, the MsrPQ system is essential for preserving membrane integrity.
The discovery and characterization of this mechanism brings many novelties. MsrPQ reduces its targets with electrons imported from the respiratory chain, a previously undescribed way of supplying reducing equivalents. The MsrPQ system is also functionally different from previously described Msr proteins, since it reduces both S- and R-diastereoisomers of methionine sulfoxide. Since the MsrPQ proteins are highly conserved in a large class of bacteria, similar systems might be present in eukaryotic oxidizing cell compartments, such as the ER.
Additionally, the defense mechanism presents an attractive target for new antibiotics, since it may further sensitize bacteria to our own immune system and oxidative stress in general. Bacterial strains lacking the MsrPQ proteins have already been shown to be less virulent then strains with the proteins intact.