Okayama University


Okayama University Medical Research Updates (OU-MRU) Vol.65

March 19, 2019

Source: Okayama University (JAPAN), Public Relations and Information Strategy

For immediate release: 18 March 2019
Okayama University research: Game changer: How do bacteria play Tag?

(Okayama, 18 March) In a recent study published in Proteins and Proteomics researchers at Okayama University show how bacteria attach to organisms before infecting them.

Bacteria have been long invading animals and plants. One of their most intricate but less understood mechanisms is their ability to adhere to other organisms. A research team led by Professor Takashi Tamura at Okayama University has unravelled the role of a molecule, DsbA, and how its chemical properties control this adhering function of bacteria.

Professor Tamura have previously shown that before bacteria can adhere to other living objects certain structures on the bacteria’s surface must be stabilized to form a strong scaffold. Special proteins found within the bacteria are responsible for this stabilization. To understand this process better, Professor Takashi Tamura’s team used a virus that attacks bacteria only (bacteriophage). This virus binds to an appendage-like structure found on the bacterial surface. DsbA is the protein responsible for stabilizing this appendage to facilitate this attachment. To decipher how DsbA does its job, the team created several mutants of bacteria, each with a different form of the DsbA protein. The code responsible for conferring DsbA a chemical charge was different in each mutant. A bacteriophage called as M13 was then introduced into these bacteria, grown on a plate.

Ideally, when M13 successfully attaches to and infects bacteria, “plaques” of viral colonies will be observed on the plate, in place of the bacterial colonies. These plaques were measured for all the different mutants. It was found that one particular mutant (DsbA [CDIC]) had 40 times more plaques than any other mutant or the unmutated bacteria. The charge on this mutant was much lower than the unmutated protein. However, another mutant, also with a low charge, did not have more plaques. This suggested that the mutated code of (DsbA [CDIC]) could be bringing about additional effects. Using structural mapping the team then found that DsbA [CDIC] had enlarged binding pockets, compared to the other variants. This could facilitate better binding of the scaffolding appendage.

Insights into these mechanisms of their attachment can help build strategies to combat bacteria. Antibiotic resistance is also spread from one bacterium to another by close contact. Designing drugs that could inactivate the factors driving DsbA function seems like one such strategy.

Proteins and structure:
Proteins that bind to and modulate the activity of other proteins are known as enzymes. Special regions on these proteins called active sites are responsible for this function. The active site consists of a ‘binding site’, a pocket where the partner protein actually binds and a ‘catalytic site’ which gives the protein a chemical charge. This charge provides the energy for the protein to undergo a chemical reaction. In the case of DsbA, codes on the catalytic site were changed to create the mutants.

Bacteriophage: Bacteriophage or “bacteria eaters” are viruses that attack and subsequently hijack bacteria. The first step in this process requires the bacteriophage to attach itself onto the bacterial surface. Typically, the bacteriophage does this by binding to F-pilus, an appendage-like structure found on the bacteria’s surface.

Shinya Sutoh, Yuko Uemura, Yuko Yamaguchi, Asako Kiyotou, Rena Sugihara, Makiko Nagayasu, Mihoko Kurokawa, Koreaki Ito, Naoki Tsunekawa, Michiko Nemoto, Kenji Inagaki, Takashi Tamura. Redox-tuning of oxidizing disulfide oxidoreductase generates a potent disulfide isomerase. Biochimica et Biophysica Acta - Proteins and Proteomics, 1867(2019), 194-201.
DOI : doi.org/10.1016/j.bbapap.2018.12.005

Correspondence to
Professor Takashi Tamura, Ph.D.
Department of Bioresources Chemistry,
Okayama University Graduate School of Environmental
and Life Science, 1-1-1, Tsushima-naka, Kita-ku, Okayama
700-8530, Japan.
E-mail: tktamura(a)okayama-u.ac.jp
For inquiries, please contact us by replacing (a) with the @ mark.

Okayama University Medical Research Updates (OU-MRU)
The whole volume : OU-MRU (1- )
Vol.1:Innovative non-invasive ‘liquid biopsy’ method to capture circulating tumor cells from blood samples for genetic testing
Vol.2:Ensuring a cool recovery from cardiac arrest
Vol.3:Organ regeneration research leaps forward
Vol.4:Cardiac mechanosensitive integrator
Vol.5:Cell injections get to the heart of congenital defects
Vol.6:Fourth key molecule identified in bone development
Vol.7:Anticancer virus solution provides an alternative to surgery
Vol.8:Light-responsive dye stimulates sight in genetically blind patients
Vol.9:Diabetes drug helps towards immunity against cancer
Vol.10:Enzyme-inhibitors treat drug-resistant epilepsy
Vol.11:Compound-protein combination shows promise for arthritis treatment
Vol.12:Molecular features of the circadian clock system in fruit flies
Vol.13:Peptide directs artificial tissue growth
Vol.14:Simplified boron compound may treat brain tumours
Vol.15:Metamaterial absorbers for infrared inspection technologies
Vol.16:Epigenetics research traces how crickets restore lost limbs
Vol.17:Cell research shows pathway for suppressing hepatitis B virus
Vol.18:Therapeutic protein targets liver disease
Vol.19:Study links signalling protein to osteoarthritis
Vol.20:Lack of enzyme promotes fatty liver disease in thin patients
Vol.21:Combined gene transduction and light therapy targets gastric cancer
Vol.22:Medical supportive device for hemodialysis catheter puncture
Vol.23:Development of low cost oral inactivated vaccines for dysentery
Vol.24:Sticky molecules to tackle obesity and diabetes
Vol.25:Self-administered aroma foot massage may reduce symptoms of anxiety
Vol.26:Protein for preventing heart failure
Vol.27:Keeping cells in shape to fight sepsis
Vol.28:Viral-based therapy for bone cancer
Vol.29:Photoreactive compound allows protein synthesis control with light
Vol.30:Cancer stem cells’ role in tumor growth revealed
Vol.31:Prevention of RNA virus replication
Vol.32:Enzyme target for slowing bladder cancer invasion
Vol.33:Attacking tumors from the inside
Vol.34:Novel mouse model for studying pancreatic cancer
Vol.35:Potential cause of Lafora disease revealed
Vol.36:Overloading of protein localization triggers cellular defects
Vol.37:Protein dosage compensation mechanism unravelled
Vol.38:Bioengineered tooth restoration in a large mammal
Vol.39:Successful test of retinal prosthesis implanted in rats
Vol.40:Antibodies prolong seizure latency in epileptic mice
Vol.41:Inorganic biomaterials for soft-tissue adhesion
Vol.42:Potential drug for treating chronic pain with few side effects
Vol.43:Potential origin of cancer-associated cells revealed
Vol.44:Protection from plant extracts
Vol.45:Link between biological-clock disturbance and brain dysfunction uncovered
Vol.46:New method for suppressing lung cancer oncogene
Vol.47:Candidate genes for eye misalignment identified
Vol.48:Nanotechnology-based approach to cancer virotherapy
Vol.49:Cell membrane as material for bone formation
Vol.50:Iron removal as a potential cancer therapy
Vol.51:Potential of 3D nanoenvironments for experimental cancer
Vol.52:A protein found on the surface of cells plays an integral role in tumor growth and sustenance
Vol.53:Successful implantation and testing of retinal prosthesis in monkey eyes with retinal degeneration
Vol.54:Measuring ion concentration in solutions for clinical and environmental research
Vol.55:Diabetic kidney disease: new biomarkers improve the prediction of the renal prognosis
Vol.56:New device for assisting accurate hemodialysis catheter placement
Vol.57:Possible link between excess chewing muscle activity and dental disease
Vol.58:Insights into mechanisms governing the resistance to the anti-cancer medication cetuximab
Vol.59:Role of commensal flora in periodontal immune response investigated
Vol.60:Role of commensal microbiota in bone remodeling
Vol.61:Mechanical stress affects normal bone development
Vol.62:3D tissue model offers insights into treating pancreatic cancer
Vol.63:Promising biomarker for vascular disease relapse revealed
Vol.64:Inflammation in the brain enhances the side-effects of hypnotic medication