@article{pmid40396485,

title = {The influence of early life exposures on the infant gut virome},

author = {Yichang Zhang and Josué L Castro-Mejía and Ling Deng and Shiraz A Shah and Jonathan Thorsen and Cristina Leal Rodríguez and Leon E Jessen and Moïra B Dion and Bo Chawes and Klaus Bønnelykke and Søren J Sørensen and Hans Bisgaard and Sylvain Moineau and Marie-Agnès Petit and Jakob Stokholm and Dennis S Nielsen},

doi = {10.1080/19490976.2025.2501194},

issn = {1949-0984},

year  = {2025},

date = {2025-12-01},

journal = {Gut Microbes},

volume = {17},

number = {1},

pages = {2501194},

abstract = {The factors influencing the establishment of the gut bacterial community in early life are fairly well studied. However, the factors shaping the infant gut virome remain elusive. Interestingly, early life gut virome imbalances have recently been linked with increased risk of developing diseases like type 1 diabetes and asthma. We utilized the deeply phenotyped COPSAC2010 cohort to investigate how environmental factors influence the gut virome at one year age. We demonstrate that the presence of older siblings as well as residential location (urban or rural) had the strongest impact on gut virome composition at 1 year of age. A total of 16,118 species-level clustered viral representative contigs (here termed viral Operational Taxonomic Units - vOTUs) were identified and of these 2105 vOTUs varied in abundance with environmental exposures. Of these vOTUs 94.1% were phages mainly predicted to infect , , and . Strong co-abundance of phages and their bacterial hosts was confirmed underlining the predicted phage-host connections. Furthermore, we found some gut viruses affected by environmental factors encode enzymes involved in the utilization and degradation of major dietary components, potentially affecting infant health by influencing the bacterial host metabolic capacity. These findings provide a valuable insights for understanding the early life factors that predispose to autoimmune and metabolic disorders.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41198952,

title = {An updated evolutionary classification of CRISPR-Cas systems including rare variants},

author = {Kira S Makarova and Sergey A Shmakov and Yuri I Wolf and Pascal Mutz and Han Altae-Tran and Chase L Beisel and Stan J J Brouns and Emmanuelle Charpentier and David Cheng and Jennifer Doudna and Daniel H Haft and Philippe Horvath and Sylvain Moineau and Francisco J M Mojica and Patrick Pausch and Rafael Pinilla-Redondo and Shiraz A Shah and Virginijus Siksnys and Michael P Terns and Jesse Tordoff and Česlovas Venclovas and Malcolm F White and Alexander F Yakunin and Feng Zhang and Roger A Garrett and Rolf Backofen and John van der Oost and Rodolphe Barrangou and Eugene V Koonin},

doi = {10.1038/s41564-025-02180-8},

issn = {2058-5276},

year  = {2025},

date = {2025-12-01},

journal = {Nat Microbiol},

volume = {10},

number = {12},

pages = {3346--3361},

abstract = {The known diversity of CRISPR-Cas systems continues to expand. To encompass new discoveries, here we present an updated evolutionary classification of CRISPR-Cas systems. The updated CRISPR-Cas classification includes 2 classes, 7 types and 46 subtypes, compared with the 6 types and 33 subtypes in our previous survey 5 years ago. In addition, a classification of the cyclic oligoadenylate-dependent signalling pathway in type III systems is presented. We also discuss recently characterized alternative CRISPR-Cas functionalities, notably, type IV variants that cleave the target DNA and type V variants that inhibit the target replication without cleavage. Analysis of the abundance of CRISPR-Cas variants in genomes and metagenomes shows that the previously defined systems are relatively common, whereas the more recently characterized variants are comparatively rare. These low abundance variants comprise the long tail of the CRISPR-Cas distribution in prokaryotes and their viruses, and remain to be characterized experimentally.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid40560955,

title = {CRISPR-Cas in the Cheese Industry},

author = {Audrey Leprince and Sylvain Moineau},

doi = {10.1146/annurev-virology-092623-111016},

issn = {2327-0578},

year  = {2025},

date = {2025-09-01},

journal = {Annu Rev Virol},

volume = {12},

number = {1},

pages = {491--512},

abstract = {Bacteria have evolved a wide range of defense systems to combat phage infections. In the cheese industry, lactic acid bacteria (LAB) used for milk fermentation continuously face threats from phages. Therefore, selecting or developing industrial strains with enhanced phage resistance requires a focus on robust defense systems. Among these systems, the clustered regularly interspaced short palindromic repeats (CRISPR) and their CRISPR-associated proteins (Cas) are notably prevalent in LAB. The early characterization of this adaptive immune system was closely tied to the cheese industry, particularly with  in which CRISPR-Cas systems are ubiquitous and highly active. This review underscores the contributions of  and its virulent phages to our understanding of the function and mechanisms of CRISPR-Cas systems. Additionally, we review the diversity of CRISPR-Cas systems in LAB used in the cheese industry, the counter-defense strategies employed by dairy phages, and the applications of CRISPR-Cas systems within this sector.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid40643002,

title = {Complete genome of five  phages},

author = {Martina Scarrone and Dann Turner and Johannes Wittmann and Christine Rohde and Simon J Labrie and Denise M Tremblay and Sylvain Moineau},

doi = {10.1128/mra.00463-25},

issn = {2576-098X},

year  = {2025},

date = {2025-08-01},

journal = {Microbiol Resour Announc},

volume = {14},

number = {8},

pages = {e0046325},

abstract = { tailed phages Bhz9, Bhz15, Bhz16, Bhz20, and Bhz21 were isolated from wastewater samples in Hamburg-Eppendorf (Germany). Their double-stranded DNA genomes range from 41,054 to 167,277 bp, encoding between 54 and 267 predicted genes, with a G + C content ranging from 36.4% to 48.9%. Only phage Bhz15 encodes tRNAs.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid40759662,

title = {Strengthening phage resistance of Streptococcus thermophilus by leveraging complementary defense systems},

author = {Audrey Leprince and Justine Lefrançois and Anne M Millen and Damian Magill and Philippe Horvath and Dennis A Romero and Geneviève M Rousseau and Sylvain Moineau},

doi = {10.1038/s41467-025-62408-3},

issn = {2041-1723},

year  = {2025},

date = {2025-08-01},

journal = {Nat Commun},

volume = {16},

number = {1},

pages = {7142},

abstract = {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.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid40377313,

title = { and  comparative analysis of 79  clinical isolates},

author = {Martina Scarrone and Dann Turner and Moïra Dion and Denise Tremblay and Sylvain Moineau},

doi = {10.1128/spectrum.02849-24},

issn = {2165-0497},

year  = {2025},

date = {2025-07-01},

urldate = {2025-07-01},

journal = {Microbiol Spectr},

volume = {13},

number = {7},

pages = {e0284924},

abstract = { is a significant nosocomial bacterial pathogen that poses a substantial infection risk due to its high resistance to antibiotics and ability to survive in hospital environments. In this study, we performed comprehensive  and  analyses on  clinical isolates from different geographical locations to uncover their genomic and epidemiological characteristics as well as their antibiotic and phage susceptibilities. Our findings revealed considerable genomic diversity among the isolates, as shown by average nucleotide identity (ANI) heat maps, multilocus sequence typing (MLST), and core genome MLST (cgMLST). We identified several international clones known for their high antibiotic resistance and global prevalence. Surprisingly, we also observed that the number of antimicrobial resistance genes (ARGs) was higher in isolates containing CRISPR-Cas systems. Plaque assays with 13 phages indicated that  phages have a narrow host range, with capsule loci (KL) serving as a good indicator of phage-bacteria interactions. The presence of CRISPR-Cas systems and other antiviral defense mechanisms in  genomes also appears to play a key role in providing phage resistance, regardless of the phage receptors. We also found that spacers associated with subtypes I-F1 and I-F2 CRISPR-Cas systems predominantly target prophages, suggesting a role in maintaining genomic stability and contributing to phage-bacteria co-evolution. Overall, this study provides a set of highly characterized  clinical isolates for future studies on antibiotic-phage-bacteria interactions.IMPORTANCE poses a significant challenge to the healthcare system due to its antibiotic resistance and strong survival mechanisms. This study examines a diverse collection of 79 clinical isolates to deepen our understanding of 's genetic characteristics and its defense mechanisms against both antibiotics and phages. Genomic analysis revealed globally prevalent, highly resistant clones and uncovered a complex role for CRISPR-Cas systems. Although CRISPR-Cas systems were not widespread among these isolates, they primarily targeted prophages. Additionally, the study emphasizes the importance of capsule types as indicators of phage susceptibility. Together, these findings provide insights into the pathogen's resilience and evolutionary adaptations, potentially guiding future research on infection control strategies and new therapeutic approaches to combat  infections.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid39733891,

title = {Lifespan and bioactivity improvement of bacteriophages immobilized on carboxymethylcellulose - Cationic starch-coated paper for food packaging},

author = {Charles Fort and Younès Bareha and Thi Thanh Ha Pham and Thanh Tung Lai and François Brouillette and Guy Njamen and Balázs Tolnai and Sylvain Moineau and Simon Barnabé},

doi = {10.1016/j.ijbiomac.2024.139138},

issn = {1879-0003},

year  = {2025},

date = {2025-03-01},

journal = {Int J Biol Macromol},

volume = {294},

pages = {139138},

abstract = {Bacteriophages (phages) have a great potential to target specifically foodborne bacterial pathogens, particularly in packaging materials. However, incorporating phages into packaging surfaces requires stabilizing their structure and maintaining their infectivity during the papermaking process. In this study, several coating formulations containing various ratios of carboxymethyl cellulose, cationic starch, and glycerol were applied to a base paper to assess phage stability. The anti-Listeria phage preparation LISTEX™ P100 was applied to the coated paper surface and then dried under a laminar airflow. Physical analyses of the base paper modifications were carried out and water absorption properties of the various coatings were analyzed. As the humidity level is also a critical factor for maintaining phage activity, the coated papers were stored at various relative humidity levels. The most effective coating for maintaining phage activity contained 2 % carboxymethylcellulose, 2 % cationic starch, and 5 % glycerol. The coated phage-containing paper was 16 μm thin, optically identical to base paper but heavier in grammage (15 % increase). The phage titers on the surface of the coating were maintained at 10 PFU/cm for 14 days when stored at 4 °C with 75 % relative humidity.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid40076628,

title = {Insight into crRNA Processing in  P42S and Application of SmutCas9 in Genome Editing},

author = {Cas Mosterd and Sylvain Moineau},

doi = {10.3390/ijms26052005},

issn = {1422-0067},

year  = {2025},

date = {2025-02-01},

journal = {Int J Mol Sci},

volume = {26},

number = {5},

abstract = {CRISPR-Cas is an adaptive immune system found in bacteria and archaea that provides resistance against invading nucleic acids. Elements of this natural system have been harnessed to develop several genome editing tools, including CRISPR-Cas9. This technology relies on the ability of the nuclease Cas9 to cut DNA at specific locations directed by a guide RNA. In addition, the nuclease activity of Cas9 requires the presence of a short nucleotide motif (5'-NGG-3' for Cas9 from ) called PAM, flanking the targeted region. As the reliance on this PAM is typically strict, diverse Cas9 variants recognising different PAM motifs have been studied to target a broader range of genomic sites. In this study, we assessed the potential of Cas9 from  strain P42S (SmutCas9) in gene editing. SmutCas9 recognises the rarely targeted 5'-NAA-3' and 5'-NGAA-3' PAMs. To test its efficacy, two genes of the virulent lactococcal phage p2 were edited, thereby demonstrating the potential of SmutCas9 for gene editing purposes, particularly in AT-rich genomes. Sequencing of total RNA also revealed the RNA components of this system, allowing further molecular characterisation of the type II-A CRISPR-Cas system of .},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid39834781,

title = {Viral niche-partitioning: comparative genomics of giant viruses across environmental gradients in a high Arctic freshwater-saltwater lake},

author = {Thomas M Pitot and Catherine Girard and Josephine Z Rapp and Vincent Somerville and Alexander I Culley and Warwick F Vincent and Sylvain Moineau and Simon Roux},

doi = {10.1093/ismeco/ycae155},

issn = {2730-6151},

year  = {2025},

date = {2025-01-01},

journal = {ISME Commun},

volume = {5},

number = {1},

pages = {ycae155},

abstract = {Giant viruses (GVs; ) impact the biology and ecology of a wide range of eukaryotic hosts, with implications for global biogeochemical cycles. Here, we investigated GV niche separation in highly stratified Lake A at the northern coast of Ellesmere Island, Nunavut, Canada. This lake is composed of a layer of ice-covered freshwater that overlies saltwater derived from the ancient Arctic Ocean, and it therefore provides a broad gradient of environmental conditions and ecological habitats, each with a distinct protist community and rich assemblages of associated GVs. The upper layer (mixolimnion) had measurable light and oxygen, and contained diverse GVs linked to photosynthetic protists, indicating adaptation to surface biotic and abiotic conditions. In contrast, the saline lower layer (monimolimnion), lacking oxygen and light, hosted GVs associated with predicted heterotrophic protists, some of which are known for a predatory lifestyle, and with several viral genes suggesting adaptation to deep-water anaerobic conditions. Our observations underscore the coupling between physical and chemical gradients, microeukaryotes and their associated GVs in Lake A, and provide insight into the potential for GVs to directly and indirectly impact host metabolism. There were similarities between the genetic composition of GVs and the metabolic processes of their potential hosts, implying co-evolution and niche-adaptation within the lake habitats. Notably, we found a greater presence of viral rhodopsins in deeper water layers, suggesting an evolutionary relationship with potential hosts capable of supplementing their energetic needs to thrive in low energy, anoxic conditions.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid39327211,

title = {The double play of a phage HTH regulator},

author = {Zacharie Morneau and Sylvain Moineau},

doi = {10.1016/j.tim.2024.09.005},

issn = {1878-4380},

year  = {2024},

date = {2024-11-01},

journal = {Trends Microbiol},

volume = {32},

number = {11},

pages = {1037--1038},

abstract = {Bacteriophages use anti-CRISPR (Acr) proteins to inhibit CRISPR-Cas systems. The expression of Acr is regulated by anti-CRISPR-associated (Aca) proteins, which are helix-turn-helix (HTH) repressors that bind DNA. Recently, Birkholz et al. discovered that an Aca can also repress Acr expression by binding RNA, revealing a new function for HTH repressors.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}