Phage therapy subjects from Sellano town : D29 phage integrase, Prophage and prophage integrase of M.ulcerans

From Wikipedia

If the target host* of a phage therapy treatment is not an animal the term "biocontrol" (as in phage-mediated biocontrol of bacteria) is usually employed, rather than "phage therapy".

"In silico"
From:"Genomics,Proteomics and Clinical Bacteriology", N.Woodford and Alan P.Johnson

Phrase that emphasizes the fact that many molecular biologists spend increasing amounts of their time in front of a computer screen, generating hypotheses that can subsequently be tested and (hopefully) confirmed in the laboratory.

Thursday, 28 August 2014

D29 phage integrase, Prophage and prophage integrase of M.ulcerans

My working hypotesis

"If before phiMU01 and phiMU02 prophages were active mycobacteriophages probably Phage integrase of D29 mycobacteri0phage (or L5) could have some common features with these prophages and with the prophage integrase inside the genome of Mycobacterium ulcerans ".
This analysis could give strength to my conviction about the presence of a new specific and unknown mycobateriophage usable in Buruli disease but at moment this phage has not been isolated in the soil or in fresch water or in other sources .

Mycobacteriophage D29

D29p32

predicted 40.0 kD protein; integrase

Integrase [DNA replication, recombination, and repair]; Region: XerC; COG0582

Phage integrase family; Region: Phage_integrase; pfam00589

Phage integrase, N-terminal SAM-like domain; Region: Phage_int_SAM_3; pfam14659

Statistics on the protein properties:

Distinguishing mark: VAL is present 27 times

Prophage integrase sequences from Mycobacterium ulcerans genome.

I have chosen MUL 0529:

MUL 0529

Site-specific recombinase XerC [DNA replication, recombination, and repair]; Region: XerC; COG4973

DNA breaking-rejoining enzymes, C-terminal catalytic domain. The DNA breaking-rejoining enzyme superfamily includes type IB topoisomerases and tyrosine recombinases that share the same fold in their catalytic domain containing six conserved active site...; Region: DNA_BRE_C; cl00213

Statistics on the protein properties:

Distinguishing mark: VAL is present 27 times

Comparison:

MUL 0529 Protein / D29p32 Protein Dot plot

D29p32 and MUL 0529 alignment

In this first part of the analysis is not clear if my working hypotesis is confirmed but if I use the observation: VAL is present 27 times, I can obtain my goal after 1 h0urs of work .

1-by Jemboss and by Wordcount software I select the word with 3 Aa but I chose only the words that contain Val Aa.
2- in the protein sequence I write all positions of VAL Aa,the start and the end of the main miscellaneous features.
3- in the protein sequence I check the positions of the words with the Val Aa.

In Position 91 in both the sequences is present VAL Aa .
In position 167 and 166 there is a VAL Aa.
LDV and TVP words are present in both the sequences and my working hypotesis is in part confirmed.

phiMU01 prophage

In the alignment with phiMU01 prophage and D29 phage integrase
I have the confirmation of my working hypotesis.

By Swiss-Model there is also the confirmation:

The reference Model :

My contribution by Discovery Studio 4.0:

Monitoring

Year 2010 (2011,2012,2013,2014,2015,2016,2017,2018..)

- At present there are Strict rules about Drugs.

Positive and continuous trend in the request of new anti-bacterial drugs.

Year 2025?- Drug regulations changes by a swing in public Opinion and Phage Therapy Units starting inside the Hospitals.

I have read a lot of scientific studies concerning different topics about Phage Therapy and many opinions from the academic world. These comments about the use of Phages in therapy are often sceptical and also sarcastic.
I share some their opinion but the trend of antibiotic resistance is characterising by a relentless advance. In the absence of new antibiotics we are obliged to act with fairness and to weigh the pros and cons of Phage therapy.

Phage Therapy is better than nothing.

Sellano is touched by History

Potential application of Mycobacterium phages in Buruli disease

I have been studying since January 2009 if Phage Therapy could be considered in Buruli ulcer. Patients shed large numbers of bacilli from their wounds.
"In the first stage of disease Mycobacterium ulcerans bacilli are typically found extracellularly, where it might be immediately accessible by phages."
Children under the age of 15 years ( range 2-14 years) are predominantly affected.
After my trip in Ivory Coast it is my personal project and I am exploring if this working hypothesis is possible.

Theory and Practical Applications of Phage Therapy in Human Field.

I must remember that Phage Therapy is not equivalent to the Antibiotic Therapy but in some pathological situations, with well definite circustances and when we have a bacterial infection caused by bacteria resistant to all antibiotics, in that case Phage Therapy would remain the unique and possible treatment with a tangible chance of succes.

A complete and schematized process for working with Phages by Phage Cocktails. Phage Therapy is praticable both in Veterinary Science and in Agricultural and Food Industry. Phage Therapy in Human field is, on the contrary, a demanding job.

I'd like to explain several key points of Phage Therapy, for example:

How to prepare Phages
How to select Phages
How to purify Phages
How to administer Phages

Patenting Issues and Defense of Intellectual Property
One relevant factor in the development of all bacteriophage-based therapies is their intellectual property status, because the idea of using bacteriophages as therapeutic tools is almost a hundred years old, and as such , unpatentable.

Main Obstacles to Phages Therapy

• Pervasive fixation on chemical antibiotics within the clinical establishment.

• Resistance of the pharmaceutical sector, which is heavily invested in chemical antibiotics.

• Physicians' reluctance to forego wide-spectrum antibiotics in favor of the highly specific phages.

• Structural and functional reorganization required for a coordinated and responsive diagnosis-production-administration chain.

• Pervasive aversion within the biotech research establishment to revert to "archaic" microbiology.

• Need to constantly adapt and refresh phage preparations in response to pathogen evolution.

• Delay between clinical presentation and antibacterial administration.

• General disregard for Russian research and clinical practices.

• Concerns with bacterial evolution of resistance to phages.

• Lack of a regulatory reference basis.

Phage therapy subjects from Sellano town

information

Phage therapy is influenced by:

From Wikipedia

Thursday, 28 August 2014

D29 phage integrase, Prophage and prophage integrase of M.ulcerans

The authentic Sellano's gonfalon (the year of 1936)

Sellano's gonfalon

The last story from Selllano's castle and its territory.Click on this image:

Phage Therapy Light and Shade

Potential application of Mycobacterium phages in Buruli disease

Plagiarism?No!But,from the Net to the Net!

Sellano's coat of arms.Click on this image:

Subject index

Links List

Call