In the human body's fight against bacterial pathogens, white blood
cells are in the front line. They identify and ingest the invaders, and
render them harmless using highly toxic substances. It is important that
these substances only destroy bacteria but cause as little collateral
damage as possible to the surrounding tissue.
Researchers from the University of Basel in Switzerland have
clarified the role of the enzyme myeloperoxidase (MPO). In fighting infections, this
enzyme, which gives pus its greenish color, produces a highly aggressive
acid that can kill pathogens without damaging the surrounding tissue.
The findings, published in the current issue of Nature Microbiology
, may provide new approaches for immunity strengthening therapies.
‘In combating bacterial infections, the enzyme myeloperoxidase (MPO) targets extremely precisely, without causing collateral damage to their surroundings.’
The research groups headed by Prof. Dirk Bumann from the Biozentrum
and Dr. Nina Khanna from the Department of Biomedicine at the University
and the University Hospital Basel discovered how white blood cells
solve this difficult task.
The enzyme myeloperoxidase attaches
directly to the surface of the bacterium where it produces an extremely
aggressive acid. The acid reacts instantly in the immediate environment,
burning a hole into the bacterial cell envelope which kills the
bacterium. In combating bacterial infections, the enzyme acts like a
sniper: Equipped with highly explosive ammunition, it targets extremely
precisely, without causing collateral damage to their surroundings.
The function of MPO - the greenish color in pus
White blood cells fight bacterial invaders by producing hydrogen
peroxide - a toxic substance, which is generally known for its use in
bleaching hair. The enzyme MPO then converts hydrogen peroxide into
hypochlorous acid. This acid, which is highly aggressive, immediately
reacts on the surface of the bacteria and kills the invader. "Bacteria
are helpless against this acid bomb," explains Dirk Bumann.
hypochloric acid is so highly reactive, the bomb reacts immediately with
the closest biomolecules. It is ignited locally and does not spread to
the wider surroundings. The bacteria die and the surrounding tissue is
spared." These findings enabled the research team to elucidate the
precise function of the enzyme MPO, which is responsible for the
greenish color seen in pus.
Long-term effects of collateral damage have not been sufficiently investigated
In their study, the researchers also investigated cells from humans
who lack the enzyme MPO due to a genetic defect. This defect affects
around one in 5000 people, making it quite rare. In these individuals,
the hydrogen peroxide is not converted into hypochlorous acid and
accumulates until it leaks out into the blood cells as well as the
"The bacteria are still killed even without MPO.
However, not only the bacteria but also the blood cells and their
surroundings are damaged," explains Bumann. "The collateral damage of
blood cells and tissues without MPO may cause long-term consequences
such as accelerated aging and cancer, but this has not yet been
systematically investigated," adds Nina Khanna.
MPO - an enzyme with two faces
"As we are confronted by fewer infections today than in the past
when MPO evolved, the collateral damage issue and its control by MPO
might play less important roles," says Khanna. On the other hand, it may
be possible to develop new treatment strategies to fight bacterial
infections, which support the immune response by strengthening the MPO
"Currently, only drugs that do the opposite and inhibit MPO
are being developed. The reason is that MPO can have negative effects in
the case of heart disease," points out Dirk Bumann. However, if such
MPO inhibitors were used broadly, patients with infections might suffer.