"French Phage Network" Annual Conference-Seventh Meeting Report.

The French Phage Network (Phages.fr) has continuously grown since its foundation, eight years ago. The annual conference, held at the Institut Pasteur in Paris, attracted 164 participants from the 11th to the 13th of October 2022.

Comparison of interferometric light microscopy with nanoparticle tracking analysis for the study of extracellular vesicles and bacteriophages.

Research on extracellular vesicles (EVs) and bacteriophages (phages) has been steadily expanding over the past decades as many of their roles in medicine, biology, and ecosystems have been unveiled. Such interest has brought about the need for new tools to quantify and determine the sizes of these biological nanoparticles. A new device based on interferometric light microscopy (ILM), the Videodrop, was recently developed for this purpose.

3-oxo-C12:2-HSL, quorum sensing molecule from human intestinal microbiota, inhibits pro-inflammatory pathways in immune cells via bitter taste receptors.

In the gut ecosystem, microorganisms regulate group behaviour and interplay with the host via a molecular system called quorum sensing (QS). The QS molecule 3-oxo-C12:2-HSL, first identified in human gut microbiota, exerts anti-inflammatory effects and could play a role in inflammatory bowel diseases where dysbiosis has been described. Our aim was to identify which signalling pathways are involved in this effect.

Gut bacteriophages and the pinball challenge.

Five years ago, my first study on the mechanisms that govern the coexistence of intestinal bacteria and bacteriophages was published in Cell Host & Microbe. In this commentary, I use the following evolutionary steps of my career to discuss the larger frame of bacteriophage biology in gut health and disease.

The intestinal virome: lessons from animal models.

Mucosal surfaces in contact with the environment host specific microbiota. The intestinal tract harbours the most abundant and diverse bacterial and viral populations interacting with each other as well as with the host. Viruses of the microbiota are important components of this ecosystem, as shown by viral alterations associated with various pathologies.

Cross-reactivity between tumor MHC class I-restricted antigens and an enterococcal bacteriophage.

Intestinal microbiota have been proposed to induce commensal-specific memory T cells that cross-react with tumor-associated antigens. We identified major histocompatibility complex (MHC) class I-binding epitopes in the tail length tape measure protein (TMP) of a prophage found in the genome of the bacteriophage Mice bearing harboring this prophage mounted a TMP-specific H-2K-restricted CD8 T lymphocyte response upon immunotherapy with cyclophosphamide or anti-PD-1 antibodies. Administration of bacterial strains engineered to express the TMP epitope improved immunotherapy in mice.

The Spatial Heterogeneity of the Gut Limits Predation and Fosters Coexistence of Bacteria and Bacteriophages.

The ecological dynamics underlying the coexistence between antagonistic populations of bacteria and their viruses, bacteriophages (phages), in the mammalian gut microbiota remain poorly understood. We challenged a murine synthetic bacterial community with phages to study the factors allowing phages-bacteria coexistence. Coexistence was not dependent on the development of phage-resistant clones nor on the ability of phages to extend their host range.

New Bacteriophages against Emerging Lineages ST23 and ST258 of and Efficacy Assessment in Larvae.

is a bacterial pathogen of high public health importance. Its polysaccharide capsule is highly variable but only a few capsular types are associated with emerging pathogenic sublineages. The aim of this work is to isolate and characterize new lytic bacteriophages and assess their potential to control infections by the ST23 and ST258 sublineages using a larvae model.

The Battle Within: Interactions of Bacteriophages and Bacteria in the Gastrointestinal Tract.

The intestinal microbiota is intimately linked to human health. Decoding the mechanisms underlying its stability in healthy subjects should uncover causes of microbiota-associated diseases and pave the way for treatment. Bacteria and bacteriophages (phages) are the most abundant biological entities in the gastrointestinal tract, where their coexistence is dynamic and affixed.

The Diversity of Bacterial Lifestyles Hampers Bacteriophage Tenacity.

Phage therapy is based on a simple concept: the use of a virus (bacteriophage) that is capable of killing specific pathogenic bacteria to treat bacterial infections. Since the pioneering work of Félix d’Herelle, bacteriophages (phages) isolated in vitro have been shown to be of therapeutic value. Over decades of study, a large number of rather complex mechanisms that are used by phages to hijack bacterial resources and to produce their progeny have been deciphered.

"I will survive": A tale of bacteriophage-bacteria coevolution in the gut.

Viruses that infect bacteria, or bacteriophages, are among the most abundant entities in the gut microbiome. However, their role and the mechanisms by which they infect bacteria in the intestinal tract remain poorly understood. We recently reported that intestinal bacteria are an evolutionary force, driving the expansion of the bacteriophage host range by boosting the genetic variability of these viruses.

The Gut Microbiota Facilitates Drifts in the Genetic Diversity and Infectivity of Bacterial Viruses.

The intestinal microbiota and human health are intimately linked, but interactions between bacteria and bacteriophages in the context of the mammalian intestine remain largely unexplored. We used comparative population genomics to study a tripartite network consisting of a virulent bacteriophage, its bacterial host, and a phage-insensitive bacterial strain both in vitro and within the murine gut. The bacteriophage adapted to infect the insensitive strain when the three partners co-existed in the gut of conventional mice, but not in dixenic mice or in planktonic cultures.

Bacteriophages Targeting Adherent Invasive Escherichia coli Strains as a Promising New Treatment for Crohn's Disease.

Background And Aims: Adherent invasive Escherichia coli [AIEC] are abnormally predominant on the ileal mucosa of Crohn's disease [CD] patients. They bind to the CEACAM6 receptor expressed on the surface of epithelial cells. We aimed to assess the potential of bacteriophages, viruses infecting bacteria, to decrease the levels of AIEC bacteria associated with the intestinal mucosa.

Bacteriophages to reduce gut carriage of antibiotic resistant uropathogens with low impact on microbiota composition.

Uropathogenic Escherichia coli (UPEC) is the leading cause of urinary tract infections (UTIs) worldwide, causing over 150 million clinical cases annually. There is currently no specific treatment addressing the asymptomatic carriage in the gut of UPEC before they initiate UTIs. This study investigates the efficacy of virulent bacteriophages to decrease carriage of gut pathogens.

Development of Photodynamic Antimicrobial Chemotherapy (PACT) for Clostridium difficile.

Background: Clostridium difficile is the leading cause of antibiotic-associated diarrhoea and pseudo membranous colitis in the developed world. The aim of this study was to explore whether Photodynamic Antimicrobial Chemotherapy (PACT) could be used as a novel approach to treating C. difficile infections.

Functional characterization of the small heat shock protein Hsp12p from Candida albicans.

Hsp12p is considered to be a small heat shock protein and conserved among fungal species. To investigate the expression of this heat shock protein in the fungal pathogen Candida albicans we developed an anti-CaHsp12p antibody. We show that this protein is induced during stationary phase growth and under stress conditions including heat shock, osmotic, oxidative and heavy metal stress.

The quorum-sensing molecules farnesol/homoserine lactone and dodecanol operate via distinct modes of action in Candida albicans.

Living as a commensal, Candida albicans must adapt and respond to environmental cues generated by the mammalian host and by microbes comprising the natural flora. These signals have opposing effects on C. albicans, with host cues promoting the yeast-to-hyphal transition and bacteria-derived quorum-sensing molecules inhibiting hyphal development.

CO(2) acts as a signalling molecule in populations of the fungal pathogen Candida albicans.

When colonising host-niches or non-animated medical devices, individual cells of the fungal pathogen Candida albicans expand into significant biomasses. Here we show that within such biomasses, fungal metabolically generated CO(2) acts as a communication molecule promoting the switch from yeast to filamentous growth essential for C. albicans pathology.

Quorum sensing and fungal-bacterial interactions in Candida albicans: a communicative network regulating microbial coexistence and virulence.

Microorganisms have evolved a complex signature of communication termed quorum sensing (QS), which is based on the exchange and sensing of low molecular- weight signal compounds. The ability to communicate within the microbial population gives the advantage to coordinate a groups behaviour leading to a higher fitness in the environment. The polymorphic fungus Candida albicans is an opportunistic human pathogen able to regulate virulence traits through the production of at least two QS signal molecules: farnesol and tyrosol.

LasI/R and RhlI/R quorum sensing in a strain of Pseudomonas aeruginosa beneficial to plants.

Pseudomonas aeruginosa possesses three quorum-sensing (QS) systems which are key in the expression of a large number of genes, including many virulence factors. Most studies of QS in P. aeruginosa have been performed in clinical isolates and have therefore focused on its role in pathogenicity.

The presence, type and role of N-acyl homoserine lactone quorum sensing in fluorescent Pseudomonas originally isolated from rice rhizospheres are unpredictable.

In Gram-negative bacteria, a typical quorum-sensing (QS) system involves the production and response to N-acyl homoserine lactones (AHLs). It still remains unclear as to how pivotal and conserved AHL QS is in root-colonizing rhizosphere Pseudomonas. We, therefore, performed a systematic study of AHL QS on a set of 50 rice rhizosphere Pseudomonas isolates.