Since a decade we are studying how virulent phages target bacterial cells within the intestinal tract of mammals using different murine models. I will briefly reviewed what we learned about phage-bacteria interactions in the gut and how this knowledge can help understanding these dynamics in relation to human health.

Phage therapy has been historically used to treat patients with bone and joint infections, with contradictory results. As bacteriophages have anti-biofilm effect, they are nevertheless promising to treat such infections, especially in the era of antimicrobial resistance. Since 2017, we implemented a multidisciplinary group dedicated to phage therapy for patients with complex bone and joint infection. We found that phage therapy has the potential to keep the function in patients with severe relapsing prosthetic joint infection. Based on our experience, identifying relevant clinical indications (such as prosthetic joint infection), and having multidisciplinary approach with international academic collaborations and interactions with national health authority and industry, are essential to go ahead and develop phage therapy in a close future.

Phages were genetically engineered to contain reporter enzymes and allow for covalent and oriented conjugation on magnetic nanoparticles. The phages were used to detect E. coli in drinking water and provided and compared favourably to current testing methods.

The talk will cover encapsulation approaches that can be used for bacteriophages including spray drying, microfluidic and membrane emulsification methods. Encapsulation affords phages protection from environmental and processing stresses. Phages administered via the oral route may lose activity upon exposure to gastric acidity and enzymatic activity. Targeted delivery and controlled release of high tires of phages may significantly improve phage treatment outcomes. Experimental results using pH triggered responsive formulations will be presented.

American Foulbrood (AFB) is a bacterial disease affecting honeybees, with no currently available treatment. The infectious process begins when adult bees provide spore-contaminated food to their larvae. We investigated the possibility of using phages to control AFB, orally administered to adult bees, by characterizing phage safety, biodistribution and activity in hive conditions.

The talk will described recent discoveries on new mechanisms by which bacteria defend themselves against phages.

Bacteria CRISPR-Cas systems provide immunity against bacteriophages and mobile genetic elements. Although some bacteria modulate CRISPR-Cas in response to population density and other factors, a lack of high-throughput methods to systematically reveal regulators has hampered efforts to understand when and how immune strategies are deployed. Here, I will discuss multiple regulatory networks controlling CRISPR-Cas immunity that we have discovered through our development and application of a robust genome-wide approach.

The molecular hijacking of the bacterial cell is driven by a remarkable diversity of phage-encoded mechanisms that modify replication, transcription and (post)translational modifications within the cell. In future, these systems may be exploited for antibacterial design strategies and biotechnological applications.

Bacteriophages frequently use cell-wall carbohydrates as specific ligands for recognition and binding, important for both entry and exit from a bacterial host cell. While phage challenge may result in altered surface glycosylation of resistant bacteria, these mutants often suffer from significant trade-offs between gain of phage insensitivity and attenuation of virulence, environmental fitness, or other properties. I will present the case of the Gram-positive pathogen Listeria monocytogenes, where phage-induced loss of specific sugars from cell wall teichoic acids results in serovar conversion and lack of cell wall-associated virulence factors.

Recombinant phage endolysins can in general access the cell wall of Gram-positive bacteria because these lack an outer membrane. Under favourable conditions, the enzymes can cut the cell wall and cause cell lysis, setting the basis for their exploration as enzybiotics. However, in conditions promoting bacterial growth, cells can be much less susceptible to endolysin attack. In this talk I will present factors involved in this endolysin tolerance and how to subvert it to improve lysis. I will also briefly mention other endolysin features that have been, so far, mostly disregarded.

We investigated plaque development by lytic phages infecting their Bacillus subtilis host. We revealed that plaque spread is limited by activation of a transient phage tolerance response in non-infected bacteria in response to lysis of their neighbors. This temporary tolerance is achieved by remodeling of bacterial surface components to restrict phage attachment.

Phages with contractile tails carry a central spike complex at the membrane-attacking end of the tail tube. Depending on the system, the central spike complex can be encoded by one, two, or three separate genes. In this talk, we will discuss the structure and function of central spike complex components.

I will talk about the extraordinary stability of recently discovered giant viruses. This work is related to developing methods to trigger capsid opening in vitro. Evolutionarily divergent giant viruses share a common biochemical mechanism. We paired this opening protocol with cryo-EM and mass spectrometry to reveal intermediates states during capsid opening and to identify the proteins released from the capsid into the cell during the initial entry step. Since these viruses are so complex, many of these proteins have no known function or structures. Therefore identifying which ones are released during entry will set us up for downstream studies to tease apart how many of these “hypothetical” viral proteins work in the life cycle of these viruses.

Tailed DNA bacteriophages are the most ubiquitous viruses on earth. Their icosahedral capsids are highly robust and stable macromolecular assemblies that contain and protect the viral genome. Despite their size diversity, phage capsids are assembled in a conserved stepwise and tightly regulated process. The large capsid of bacteriophage T5 is a model of choice to understand the molecular mechanisms sustaining the sequential events that take place during capsid assembly. I will discuss how this knowledge opens avenues in engineering nanocarriers of major therapeutic and biotechnological interest.

The most widespread human phage - crAssphage - has been found in 2/3 of the countries on the planet so far, but the genomic signatures belie global dissemination and demonstrate unique regional and local evolution.

Haptophytes are key components of the phytoplankton community in the ocean, playing important roles both as primary producers and as mixotrophs that graze on bacteria and protists. In this talk I will discuss the adaptive evolution of haptophyte-infecting viruses, from those that cause acute infections to those that stably coexist with their host, and identify traits of importance for successful survival in the ocean.

CrAssphage are the most abundant bacteriophage in the human gut, representing more than 90% of the total phage population in some individuals. It is an unusual phage that has co-evolved with the human microbiome and has an unusual lifestyle in that it co-exists with its bacterial host in high numbers. I will discuss our progress so far in understanding this abundant but elusive phage.