A protein containing a metal complex for blue paint inhibits growth of a pathogenic bacterium through iron deprivation
Nagoya, Japan – Professor Yoshihito Watanabe (WPI-ITbM, Cooperating Researcher), Associate Professor Osami Shoji, Ms. Chikako Shirataki of Nagoya University and co-workers have found a new method using an artificial metalloprotein (a protein that contains a metal) to inhibit the growth of Pseudomonas aeruginosa bacteria, which is a common bacterium that can cause diseases in humans and evolves to exhibit multiple antibiotic resistance.
Figure 1. Heme iron capturing mechanism of P. aeruginosa bacteria by HasA protein.
Copyright : Nagoya University
The inhibition of growth has been achieved through the deprivation of iron uptake using an artificial metalloprotein. The study published in the online Early View on February 7, 2014 of Angewandte Chemie International Edition, is expected to bring hope in the battle against bacteria.
P. aeruginosa bacteria exists in many aquatic areas and is prevalent in hospitals. Although they do not usually affect healthy people, they increase the risk for infection of patients with low immunity. Their high resistance towards many antibiotics makes complete elimination of them extremely difficult. Like humans, bacteria require the uptake of heme iron for their survival, and a protein (HasA) is secreted from bacteria to capture heme from its host. The heme-bound HasA protein transfers heme via receptor proteins on the cell surface of the bacterium, P. aeruginosa (Figure 1).
“Upon looking closely at the crystal structure of the HasA protein binding heme, we considered the possibility of the HasA protein to bind to a metal complex that has a similar structure as heme” says Associate Professor Osami Shoji, who led the study. “We found synthetic metal complexes that can mimic heme and bind to the HasA protein. To our delight, one of the resulting complexes successfully inhibited growth of P. aeruginosa bacteria.”
“It took us around four years to discover that phthalocyanine, which is a blue paint used on the surface of the Japanese bullet trains and road signs, could bind competitively to the HasA protein”, adds Ms. Chikako Shirataki, a PhD student in her final year, “crystal structures of metal protein complexes helped us to show that the phthalocyanine-bound HasA protein blocks the receptors on the cell surface of the bacterium and thus, inhibits the uptake of heme.” When bacteria are deprived of iron, further growth of the bacteria is inhibited (Figure 2).
P. aeruginosa infections can potentially lead to pneumonia and an effective treatment method is highly required. This finding by Shoji’s group opens new doors to treat P. aeruginosa infections by using an unprecedented approach to inhibit the growth of bacteria. Associate Professor Shoji states, “With the advice of medical doctors, we are currently working to develop a new system to wipe out bacteria by tuning various metal complexes. Although the efficiency is not high yet, we have already established a mechanism to eliminate bacteria and we are considering how to apply it to different cases.”
ichi Ozaki, Hiroshi Sugimoto, Yoshitsugu Shiro, Yoshihito Watanabe, is published in the Early View on February 7, 2014 in Angewandte Chemie International Edition. The article was selected as an inside cover. DOI: 10.1002/anie.201307889
This work was conducted with Mitsuyoshi Terada of Nagoya University, Professor Shin-ichi Ozaki of Yamaguchi University, Dr. Hiroshi Sugimoto and Professor Yoshitsugu Shiro of RIKEN SPring-8 Center, Harima Institute.
Associate Professor Osami Shoji
Department of Chemistry, Graduate School of Science, Nagoya University
Furo-Cho, Chikusa-ku, Nagoya 464-8602, Japan
Public Relations Contact
Dr. Ayako Miyazaki
Institute of Transformative Bio-Molecules (WPI-ITbM), Nagoya University
Furo-Cho, Chikusa-ku, Nagoya 464-8601, Japan
TEL: +81-52-789-4999 FAX: +81-52-789-3240
Nagoya University Public Relations Office TEL: +81-52-789-2016 FAX: +81-52-788-6272
Angewandte Chemie International Edition
Ayako Miyazaki | Research SEA
Unique genome architectures after fertilisation in single-cell embryos
30.03.2017 | IMBA - Institut für Molekulare Biotechnologie der Österreichischen Akademie der Wissenschaften GmbH
Transport of molecular motors into cilia
28.03.2017 | Aarhus University
The Institute of Semiconductor Technology and the Institute of Physical and Theoretical Chemistry, both members of the Laboratory for Emerging Nanometrology (LENA), at Technische Universität Braunschweig are partners in a new European research project entitled ChipScope, which aims to develop a completely new and extremely small optical microscope capable of observing the interior of living cells in real time. A consortium of 7 partners from 5 countries will tackle this issue with very ambitious objectives during a four-year research program.
To demonstrate the usefulness of this new scientific tool, at the end of the project the developed chip-sized microscope will be used to observe in real-time...
Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.
The results will be published on March 22 in the journal „Astronomy & Astrophysics“.
Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...
Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.
Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...
In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...
20.03.2017 | Event News
14.03.2017 | Event News
07.03.2017 | Event News
30.03.2017 | Health and Medicine
30.03.2017 | Health and Medicine
30.03.2017 | Medical Engineering