The
Bombina variegata frog, also known as Yellow Bellied Toad, inhabits the
forests, grasslands, wetland, and aquatic habitats across Central Europe. Their
skin secretions contain antimicrobial agents -- called Bominin H2 and H4 --
that play a key role in protecting the species against infection.
Bombinin
H2 and H4 are antimicrobial peptides (AMPs) -- or host defense peptides -- that
play an important function in immune response. They have attracted attention
for their ability to inhibit Leishmaniasis -- a highly infectious and
potentially fatal tropical disease that has affected an estimated 20 million
people worldwide, with 1.3 million new cases and 20,000 to 30,000 deaths
reported each year.
In
order to gain a better understanding of the molecular mechanism that drives the
antimicrobial activity of Bombinin H2 and H4 peptides and what makes H4 more
effective than H2 in this regard, the authors conducted electrophysiological
experiments on a lipid bilayer membrane that replicated the lipid membrane
surrounding cells or microorganisms The results were then analyzed using
existing AMP models to determine how efficient these antimicrobial peptides are
at disrupting the cell membrane of microbes.
The
team found that H2 and H4 peptides inhibit microbial activity by making holes
in the cell membrane of microorganisms, causing ions to leak out of the cell,
which ultimately kills them. The efficiency of this anti-microbial activity is
affected by ion permeability (how fast ions leak out of the cell), the speed of
pore formation, and the size of the pores formed.
The
results indicate that the peptides' ability to transform into another molecule
with the same atomic composition but with atoms arranged differently
facilitates faster pore formation. While H2 forms larger pores than H4, H4
forms pores more rapidly. A mixture of H2/H4, meanwhile, forms medium-sized
pores at a slower rate than H4, but the presence of the D-amino acid enhances
the binding affinity to the lipid membrane, thereby improving its disruptive
abilities.
In
terms of what this means, think of it like a field of different sized pit
traps; larger traps take longer to dig, but can trap more animals than a
smaller pit. On the other hand, one can dig many smaller pits in the same time
it takes to dig just a few large ones. Digging medium sized pit traps and
adding bait or a lure that would attract animals to the pit, would be the most
effective approach of all.
Unravelling
the molecular mechanism that facilitates antimicrobial activity of these
peptides can help us better understand how the defense system of the frog has
evolved, and how this can be used to fight microbial infections of medical
importance.
The
ultimate goal is to use this mechanism to develop better antimicrobial agents,
especially antimicrobial agents that are effective against antibiotic-resistant
bacteria.
Reference:
Posted by Dr. Tim Sandle, Pharmaceutical Microbiology
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