Using the bio-diversity and bio-specificity of the DSMZ
The open DSMZ collection of bacteria and Archaea is known for its broad diversity but also for some world-wide unique specialized collections, their curators are renowned experts. For this diversity on the one hand and the specialty on the other hand, a substantial extension of the bacteriophage collection is a true demand! Bacteriophages (phages) can probably be found for all species, they are the viruses of the bacteria and usually highly specific for one bacterial species or some strains of a species.
Why phages? Their role for research and application has been recognised again during the past few years: obligately lytic phages can be useful “tools” where bacteria cause problems, phages have a potential for application that cannot be overestimated. Temperate phages can integrate into the host’s genome as prophages and change between a lytic and a lysogenic cycle and can sometimes also change hosts. Because of this “mobility” they bear a great potential of open research questions. Such phages are able to transmit parts of the host’s genome and hence, they are driving forces of biodiversification processes in all kinds of habitats, e.g. ocean water, sediments, soil, mud, all kinds of water reservoirs, extreme habitats and also of the human, animal or plant microbiomes. Phages and bacteria are co-existing in a balance, they develop in co-evolution. The number of phages depends on the availability of their hosts, this is one aspect of evolution dynamics. Natural systems like wind or water carry bacteria and phages in huge amounts through the biosphere and mix continuously the gigantic gene pool of phage-bacteria systems.
The earth has been designated a planet of phages: phages are the most abundant living entities, experts estimated their particle number at about 1031, tenfold the number of bacteria. The human microbiome, the complete microbial community within and on the human body, bears about estimated 1014 bacteria, tenfold the number of cells of the body. But, also pathogenic bacteria can colonise this microbiome. Phages would often have the power to rescue life (hospital infections). Today, pathogenic bacteria that occur in the industrial livestock farming develop to be serious zoonotic disease-causing agents. Huge amounts of antibiotic substances are applied there; this has become one of the main causes of the vicious circle of multiresistances against antibiotics. Also, plant-pathogenic bacteria could be eradicated by applying phages, without side effects. Bacteria easily colonise food, especially on surfaces. Listeria monocytogenes, a dangerous pathogen, can contaminate cheese, phages are already successfully used to prevent such food contamination. Furthermore, phages can be used as indicators, e.g. for fecal bacteria. Without doubt, the useful potential of phages is much higher and therefore, broad phage diversity is an important aim of the DSMZ. It is also fundamental for research projects to establish a big pool of phages and to maintain them authentic and stable for future generations.
Phages at the DSMZ
Because of the phage expertise the DSMZ was leading a work package under the EU project CABRI to develop methodological quality guidelines for phage collections. This expertise is one of the DSMZ’s unique features: the DSMZ has been acknowledged to have the leading role in Europe in this area, together with two other well-known centres in the USA and Canada. Internationally, a growing interest in phages can be observed. The repertoire of bacteria and Archaea held at the DSMZ means a profound basis for a substantial extension of the phage collection, as a pool for biodiversity research and as a pool for phage screening to select phages for practical applications. It is a must in biodiversity research to look at the role of phages. One of DSMZ’s key aspects are medically relevant bacteria, also in the context of DZIF consortium (Deutsches Zentrum für Infektionsforschung, German Centre for Infection Research). The most obvious application of lytic phages is in the medical area: phages can help when antibiotics against multiresistant pathogens become ineffective. MRSA (Methicillin-resistant Staphylococcus aureus) and ESBL (Extended Spectrum Beta-Lactamases) bacteria are the most wellknown and much-feared examples. These bacteria cause many thousands of deadly nosocomial infections in Germany and elsewhere (annual reports of the Robert-Koch Institute). In collaboration with the Eliava Institute IBMV, Tbilisi, Georgia, the DSMZ has finished a phage project to fight against MRSA. One actual phage research focus at the DSMZ aims at bacteria of the order Burkholderiales that play a role in the biofilms of patients’ lungs suffering from COPD (chronically obstructive pulmonary disease) or cystic fibrosis. Besides enlarging the phage diversity for as many bacterial phyla as possible, the DSMZ focuses on the collection of phages against pathogens. The DSMZ provides the phage diversity for the scientific community in controlled high-titre quality, phages are preserved according to two methods for the long-term. Host spectra of many phages are checked, one of the main parameters of a phage. In close vicinity to the DSMZ, phage morphology can be examined at the HZI (Helmholtz-Zentrum für Infektionsforschung, Helmholtz Centre for Infection Research). State-of-the-art genomics with bio-informatic analyses can be done at the DSMZ.
Phage trapper with the DSMZ: Students take part in biodiversity research
In the scientific community and in the public community as well, phages shall become important key topic: i) by way of an application perspective: how can phages be used as active substances? and ii) by way of the perspective in fundamental research: which new phages can be isolated from the phage world? Both perspectives require clear framing of target bacteria to be selected. This is a call to universities to take part and help select these phage targets! The initiative, together with universities shall extend DSMZ’s phage holdings significantly. It shall contribute to gain deeper insight into the role of phages in the complexity of biodiversity. Students’ curricula shall be designed to screen habitats for new phages under the guiding motif ”There are only interesting phages”. Characterising including genome sequencing and molecular description towards systems biology (phage-host interrelation) are superior aims but actually, integrating new phages into the open collection and making them available is superficial.
The DSMZ invites Universities to take part in the continuous Project Phage Collectors. The Technical University of Braunschweig, The University of Bielefeld, the University of Göttingen, the University of Hohenheim, the University of Saarbrücken and The Fachhochschule Südwestfalen, Iserlohn, have started with this collaboration.
For the students‘ academic education, the project provides the following useful aspects:
- Students will be introduced into fundamental microbiological methods and bacterial diversity, selected target bacteria for phage screening will be provided by the DSMZ
- The DSMZ will offer the required course protocols
- Students can explore habitats, e.g. sewage water, other kinds of water sources, soil
- Students can give names to the new phages they found; such phages are often interesting enough to be published and students will be the official depositors with the DSMZ
- J. Barylski et al.: Analysis of Spounaviruses as a Case Study for the Overdue Reclassification of Tailed Phages. Syst Biol. (2019)
- I. Korf et al.: Still Something to Discover: Novel Insights into Escherichia coli Phage Diversity and Taxonomy. Viruses. (2019)
- J. Akhwale et al.: Isolation, characterization and analysis of bacteriophages from the haloalkaline lake Elmenteita, Kenya. PLoS One. (2019)
- J. Akhwale et al.: Comparative genomic analysis of eight novel haloalkaliphilic bacteriophages from Lake Elmenteita, Kenya. PLoS One. (2019)
- C. Rohde et al.: Bacteriophages: A Therapy Concept against Multi-Drug-Resistant Bacteria. Surg Infect (2018)
- N. Hoyle et al.: Phage therapy against Achromobacter xylosoxidans lung infection in a patient with cystic fibrosis: a case report. Res Microbiol. (2018)
- E. Adriaenssens et al.: Taxonomy of prokaryotic viruses: 2017 update from the ICTV Bacterial and Archaeal Viruses Subcommittee. Arch Virol. (2018)
- W. Sybesma et al.: Silk Route to the Acceptance and Re-Implementation of Bacteriophage Therapy-Part II. Expert round table on acceptance and re-implementation of bacteriophage therapy. Antibiotics. (2018)
- C. Rohde et al.: Expert Opinion on Three Phage Therapy Related Topics: Bacterial Phage Resistance, Phage Training and Prophages in Bacterial Production Strains. Viruses (2018)
- B. Dreiseikelmann et al.: Characterization and genome comparisons of three Achromobacter phages of the family Siphoviridae. Arch Virol. (2017)
- L. Debarbieux et al.: A bacteriophage journey at the European Medicines Agency. FEMS Microbiol Lett. (2016)
- J.-P. Pirnay et al.: Quality and safety requirements for sustainable phage therapy products. Pharm Res. (2015)
- J. Wittmann et al.: Taxonomic reassessment of N4-like viruses using comparative genomics and proteomics suggests a new subfamily - "Enquartavirinae". Arch Virol. (2015)
- H. Beims et al.: Paenibacillus larvae-Directed Bacteriophage HB10c2 and Its Application in American Foulbrood-Affected Honey Bee Larvae. Appl Environ Microbiol. (2015)
- J. Wittmann et al.: Isolation and Characterization of Numerous Novel Phages Targeting Diverse Strains of the Ubiquitous and Opportunistic Pathogen Achromobacter xylosoxidans. PLoSone (2014)
- J. Wittmann et.al : First genome sequences of Achromobacter phages reveal new members of the N4 family. Virology Journal (2014), 11:14 http://www.virologyj.com/content/11/1/14
- K. Selezska et al.: Pseudomonas aeruginosa population structure revisited under environmental focus: impact of water quality and phage pressure. Environ. Microbiol. (2012)
- L. Kvachadze et al.: Evaluation of lytic activity of staphylococcal bacteriophage Sb-1 against freshly isolated clinical pathogens. Microbial Biotechnol. (2011)
- C. Rohde & J. Sikorski: Bakteriophagen – Vielfalt, Anwendung und ihre Bedeutung für die Wissenschaft vom Leben. Naturwiss. Rundschau (2011)