The phage life cycle is a multi-stage process initiated by the recognition and attachment of the virus to its bacterial host. This adsorption step depends on the specific interaction between bacterial structures acting as receptors and viral proteins called Receptor Binding Proteins (RBP). The adsorption process is essential as it is the first determinant of phage host range and a sine qua non condition for the subsequent conduct of the life cycle. In phages belonging to the Caudoviricetes class, the capsid is attached to a tail, which is the central player in the adsorption as it comprises the RBP and accessory proteins facilitating phage binding and cell wall penetration prior to genome injection. The nature of the viral proteins involved in host adhesion not only depends on the phage morphology (i.e., myovirus, siphovirus, or podovirus) but also the targeted host. Here, we give an overview of the adsorption process and compile the available information on the type of receptors that can be recognized and the viral proteins taking part in the process, with the primary focus on phages infecting Gram-positive bacteria.

CRISPR-Cas and restriction-modification systems represent the core defense arsenal in Streptococcus thermophilus, but their effectiveness is compromised by phages encoding anti-CRISPR proteins (ACRs) and other counter-defense strategies. Here, we explore the defensome of 263 S. thermophilus strains to uncover other anti-phage systems. The defense landscape of S. thermophilus is enriched by 21 accessory defense systems, 13 of which have never been investigated in this species. Experimental validation of 17 systems with 14 phages reveals a range of anti-phage activities, highlighting both broad and narrow specificities across the five viral genera infecting S. thermophilus. Synergies are observed when combining CRISPR immunity with accessory systems. We also assess the fitness cost associated with the chromosomal integration of these systems in their native context and find no impact under laboratory or industrial conditions. These findings underscore the potential of these accessory defense systems to enhance the resistance of S. thermophilus, particularly against ACR-encoding phages.

Bacteriophages, viruses infecting bacteria, are estimated to outnumber their cellular hosts by 10-fold, acting as key players in all microbial ecosystems. Under evolutionary pressure by their host, they evolve rapidly and encode a large diversity of protein sequences. Consequently, the majority of functions carried by phage proteins remain elusive. Current tools to comprehensively identify phage protein functions from their sequence either lack sensitivity (those relying on homology for instance) or specificity (assigning a single coarse grain function to a protein). Here, we introduce Empathi, a protein-embedding-based classifier that assigns functions in a hierarchical manner. New categories were specifically elaborated for phage protein functions and organized such that molecular-level functions are respected in each category, making them well suited for training machine learning classifiers based on protein embeddings. Empathi outperforms homology-based methods on a dataset of cultured phage genomes, tripling the number of annotated homologous groups. On the EnVhogDB database, the most recent and extensive database of metagenomically-sourced phage proteins, Empathi doubled the annotated fraction of protein families from 16% to 33%. Having a more global view of the repertoire of functions a phage possesses will assuredly help to understand them and their interactions with bacteria better.

The phage life cycle ends with the host cell lysis, thereby releasing new virions into the environment for the next round of bacterial infection. Nowadays, there is renewed interest in phages as biocontrol agents, primarily due to their ability to cause bacterial death through lysis.

The B. cereus group is a complex cluster of closely related species, among which certain strains can be pathogenic (i.e., Bacillus anthracis , Bacillus cereus sensu stricto , and Bacillus cytotoxicus ). Nowadays, phages are receiving increasing attention for applications in controlling and detecting such pathogens.