Nav: Home

Study unravels mystery of antimicrobial frog secretions

April 23, 2019

Japanese scientists including researchers at Tokyo University of Agriculture and Technology (TUAT) and Yokohama National University have identified the molecular mechanism that gives the skin secretions of a species of frog effective antimicrobial properties.

Their findings were published on February 20, 2019 in ACS Applied Bio Materials.

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.

H4 is an isomer of H2 - they share the same formula but the atoms in the molecule are arranged differently - with H4 having a naturally occuring D-amino acid at the end of the molecular chain. In terms of its antimicrobial properties, H4 is more potent than H2, but until now, the reason has remained an unsolved biological mystery.

"D- and L-amino acids are mirror images of each other, and most amino acids in nature have L structure," explains Ryuji Kawano, Associate Professor in the Department of Biotechnology and Life Science at TUAT and co-author of the study. "A few proteins are modified to have D-amino acids. The role of having D-amino acids is not fully understood in case of the frog."

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.

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. According to Kawano, the ultimate goal is to use this mechanism to develop better antimicrobial agents, especially antimicrobial agents that are effective against antibiotic-resistant bacteria.
-end-
About Tokyo University of Agriculture and Technology (TUAT)

TUAT is a distinguished university in Japan dedicated to science and technology. TUAT focuses on agriculture and engineering that form the foundation of industry, and promotes education and research fields that incorporate them. Boasting a history of over 140 years since our founding in 1874, TUAT continues to boldly take on new challenges and steadily promote fields. With high ethics, TUAT fulfills social responsibility in the capacity of transmitting science and technology information towards the construction of a sustainable society where both human beings and nature can thrive in a symbiotic relationship. For more information, please visit http://www.tuat.ac.jp/en/.

Original publication:

Yusuke Sekiya, Keisuke Shimizu, Yuki Kitahashi, Akifumi Ohyama, Izuru Kawamura, and Ryuji Kawano. " Electrophysiological Analysis of Membrane Disruption by Bombinin and Its Isomer Using the Lipid Bilayer System", ACS Appl. Bio Mater., 2019, 2 (4), pp 1542-1548, DOI: 10.1021/acsabm.8b00835

Contact:

Ryuji Kawano, Dr.,
Associate Professor,
Department of Biotechnology and Life Science,
Tokyo University of Agriculture and Technology.
Email: rjkawano@cc.tuat.ac.jp

For more information about the Kawano laboratory, please visit http://web.tuat.ac.jp/~rjkawano/en.html

Tokyo University of Agriculture and Technology

Related Peptides Articles:

Origin of life insight: peptides can form without amino acids
Peptides, one of the fundamental building blocks of life, can be formed from the primitive precursors of amino acids under conditions similar to those expected on the primordial Earth, finds a new UCL study published in Nature.
Ragon Institute study identifies viral peptides critical to natural HIV control
Investigators at the Ragon Institute of MGH, MIT and Harvard have used a novel approach to identify specific amino acids in the protein structure of HIV that appear critical to the ability of the virus to function and replicate.
Light and peptides: New method diversifies natural building blocks of life
EPFL chemists have developed a new, light-based method for modifying peptides at the C-terminal position.
Peptides with brominated tryptophan analogs could protect marine animals
Bromotryptophan is a nonstandard amino acid that is rarely incorporated in ribosomally synthesized and post-translationally modified peptides (ribosomal peptides).
About TFE: Old and new findings
The fluorinated alcohol 2,2,2-Trifluoroethanol (TFE) has been implemented for many decades now in conformational studies of proteins and peptides.
CRISPR reveals the secret life of antimicrobial peptides
Using CRISPR, scientists at EPFL have carried out extensive work on a little-known yet effective weapon of the innate immune system, antimicrobial peptides.
Nanopores make portable mass spectrometer for peptides a reality
University of Groningen scientists have developed nanopores that can be used to directly measure the mass of peptides.
Dry-cured ham bones -- a source of heart-healthy peptides?
Drinking bone broth is a recent diet fad that proponents claim fights inflammation, eases joint pain and promotes gut health.
Natural-based antibiofilm and antimicrobial peptides from microorganisms
The exploration of AMP and antibiofilm peptide (ABP) producer microorganisms brings with it a lot of challenges experimentally.
A boundary dance of amyloid-β stepping into dementia
Alzheimer's disease is caused by aggregates of amyloid-β (Aβ) peptides.
More Peptides News and Peptides Current Events

Top Science Podcasts

We have hand picked the top science podcasts of 2019.
Now Playing: TED Radio Hour

Risk
Why do we revere risk-takers, even when their actions terrify us? Why are some better at taking risks than others? This hour, TED speakers explore the alluring, dangerous, and calculated sides of risk. Guests include professional rock climber Alex Honnold, economist Mariana Mazzucato, psychology researcher Kashfia Rahman, structural engineer and bridge designer Ian Firth, and risk intelligence expert Dylan Evans.
Now Playing: Science for the People

#541 Wayfinding
These days when we want to know where we are or how to get where we want to go, most of us will pull out a smart phone with a built-in GPS and map app. Some of us old timers might still use an old school paper map from time to time. But we didn't always used to lean so heavily on maps and technology, and in some remote places of the world some people still navigate and wayfind their way without the aid of these tools... and in some cases do better without them. This week, host Rachelle Saunders...
Now Playing: Radiolab

Dolly Parton's America: Neon Moss
Today on Radiolab, we're bringing you the fourth episode of Jad's special series, Dolly Parton's America. In this episode, Jad goes back up the mountain to visit Dolly's actual Tennessee mountain home, where she tells stories about her first trips out of the holler. Back on the mountaintop, standing under the rain by the Little Pigeon River, the trip triggers memories of Jad's first visit to his father's childhood home, and opens the gateway to dizzying stories of music and migration. Support Radiolab today at Radiolab.org/donate.