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The WHO estimates up to 700,000 patients died in of multidrug resistant bacterial infections globally in 2016. This rise of multidrug resistant bacteria, prompted researchers to explore phage therapy again with spectacular successes. Several publications have recently reported spectacular successes in the fight against multidrug resistant bacterial infections in humans but also life stock. While in the past phage therapy was shunned by pharma companies for various challenges, now the commercial potential and advances in genetics have enticed biotech companies to exploit the potential of phage therapy as a secret weapon to kill superbugs.

More than 100 years ago the French scientist Felix d’Herelle identified bacteriophages! They look like spaceships from another world and are most fearsome killing machines, fortunately they are targeting exclusively bacteria. D’Herelle and his colleague George Eliava immediately realised phages could be weaponised to help patients to fight off bacterial infections. However, in the western hemisphere the control of life-threatening bacterial infections was soon achieved with antibiotics, while phages and viruses became favourite research tools of geneticists. This explains why the bacteriophage T4, which is depicted here, is one of the most intensely studied biological objects. However, phage therapy was pioneered by the Eliava Institute in Georgia, where it has been advanced ever since its discovery.

Phages stick to bacteria with their leg-like fibres, which triggers a change in the protein conformation ramming their shaft into the bacterial hull. The interior of the shaft contains a needle, which punctures the bacterial envelope enabling the phage to inject its genetic material. The phage genome within minutes overcomes the bacterial defences, phage components are assembled within the cell before it ruptures to release a new wave of phages. Several biotech companies are now ready to exploit the deadly potential of phage therapy as a secret weapon to kill superbugs.

Phagetherapy frequently relies on extensive phage collections. One of them is maintained with the support of students searching phages, which can be found virtually everywhere. SEA-PHAGES (https://seaphages.org/) is a two-semester, discovery-based undergraduate research course that begins with simple digging in the soil to find new viruses, but progresses through a variety of microbiology techniques and eventually to complex genome annotation and bioinformatic analyses. It hzas assembled under the supervision of Graham Hatfull’s group at the University of Pittsburgh and the Howard Hughes Medical Institute’s Science Education division a collection of more than 15.000 phages.

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References:

WHO on antimicrobial resistant bacteria: https://www.who.int/…/fact-…/detail/antimicrobial-resistance

The dawn of phage therapy. Sana Rehman et al. https://doi.org/10.1002/rmv.2041

Engineered bacteriophages for treatment of a patient with a disseminated drug-resistant Mycobacterium abscessus. Rebekah M. et al. Nature Medicine volume 25, pages730–733 (2019) https://www.nature.com/articles/s41591-019-0437-z

Specific and Selective Bacteriophages in the Fight against Multidrug-resistant Acinetobacter baumannii. Bagińska N, et al. Virol Sin. 15. doi: 10.1007/s12250-019-00125-0.

Successful adjunctive use of bacteriophage therapy for treatment of multidrug-resistant Pseudomonas aeruginosa infection in a cystic fibrosis patient. Law N, et al., Infection. 2019 May 17. doi: 10.1007/s15010-019-01319-0.

Synergistic effect of phage therapy using a cocktail rather than a single phage in the control of severe colibacillosis in quails. Naghizadeh M et al., Poult Sci. 2019 Feb 1;98(2):653-663. doi: 10.3382/ps/pey414.