Strengthening phage resistance of Streptococcus thermophilus by leveraging complementary defense systems
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...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-08-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-62408-3 |
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| author | Audrey Leprince Justine Lefrançois Anne M. Millen Damian Magill Philippe Horvath Dennis A. Romero Geneviève M. Rousseau Sylvain Moineau |
| author_facet | Audrey Leprince Justine Lefrançois Anne M. Millen Damian Magill Philippe Horvath Dennis A. Romero Geneviève M. Rousseau Sylvain Moineau |
| author_sort | Audrey Leprince |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-cfe95623a86f4f35b87fb745c4d782ed |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-cfe95623a86f4f35b87fb745c4d782ed2025-08-20T03:46:15ZengNature PortfolioNature Communications2041-17232025-08-0116111610.1038/s41467-025-62408-3Strengthening phage resistance of Streptococcus thermophilus by leveraging complementary defense systemsAudrey Leprince0Justine Lefrançois1Anne M. Millen2Damian Magill3Philippe Horvath4Dennis A. Romero5Geneviève M. Rousseau6Sylvain Moineau7Département de biochimie, de microbiologie et de bio-informatique, Faculté des sciences et de génie, Université Laval, Québec City, QC, Canada. Institut de Biologie Intégrative et des Systèmes (IBIS), Pavillon Charles-Eugène-Marchand, Université LavalDépartement de biochimie, de microbiologie et de bio-informatique, Faculté des sciences et de génie, Université Laval, Québec City, QC, Canada. Institut de Biologie Intégrative et des Systèmes (IBIS), Pavillon Charles-Eugène-Marchand, Université LavalIFF Health and Biosciences, 3329 Agriculture DrIFF Health and Biosciences, CS 10010IFF Health and Biosciences, CS 10010IFF Health and Biosciences, 3329 Agriculture DrDépartement de biochimie, de microbiologie et de bio-informatique, Faculté des sciences et de génie, Université Laval, Québec City, QC, Canada. Institut de Biologie Intégrative et des Systèmes (IBIS), Pavillon Charles-Eugène-Marchand, Université LavalDépartement de biochimie, de microbiologie et de bio-informatique, Faculté des sciences et de génie, Université Laval, Québec City, QC, Canada. Institut de Biologie Intégrative et des Systèmes (IBIS), Pavillon Charles-Eugène-Marchand, Université LavalAbstract 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.https://doi.org/10.1038/s41467-025-62408-3 |
| spellingShingle | Audrey Leprince Justine Lefrançois Anne M. Millen Damian Magill Philippe Horvath Dennis A. Romero Geneviève M. Rousseau Sylvain Moineau Strengthening phage resistance of Streptococcus thermophilus by leveraging complementary defense systems Nature Communications |
| title | Strengthening phage resistance of Streptococcus thermophilus by leveraging complementary defense systems |
| title_full | Strengthening phage resistance of Streptococcus thermophilus by leveraging complementary defense systems |
| title_fullStr | Strengthening phage resistance of Streptococcus thermophilus by leveraging complementary defense systems |
| title_full_unstemmed | Strengthening phage resistance of Streptococcus thermophilus by leveraging complementary defense systems |
| title_short | Strengthening phage resistance of Streptococcus thermophilus by leveraging complementary defense systems |
| title_sort | strengthening phage resistance of streptococcus thermophilus by leveraging complementary defense systems |
| url | https://doi.org/10.1038/s41467-025-62408-3 |
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