A mutation in the methionine aminopeptidase gene provides phage resistance in Streptococcus thermophilus

Labrie, Simon J.; Mosterd, Cas; Loignon, Stéphanie; Dupuis, Marie-Ève; Desjardins, Philippe; Rousseau, Geneviève M.; Tremblay, Denise M.; Romero, Dennis; Horvath, Philippe; Fremaux, Christophe; Moineau, Sylvain

doi:10.1038/s41598-019-49975-4

Cited by 19 publications

(10 citation statements)

References 56 publications

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“…Phage adsorption assays revealed that in parallel to spacer acquisition, surface receptor mutations likely also play a role in phage resistance in S. mutans. This finding is in sharp contrast to those for S. thermophilus, where surface receptor mutations are less frequent (36,37). The receptor for phage M102AD is currently not known, and no universal mutation responsible for adsorption resistance could be found.…”

Section: Discussioncontrasting

confidence: 72%

Characterization of a Type II-A CRISPR-Cas System in Streptococcus mutans

Mosterd

Moineau

2020

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Streptococcus mutans and its virulent phages are important members of the human oral microbiota. S. mutans is also the primary causal agent of dental caries. To survive in this ecological niche, S. mutans must encode phage defense mechanisms, which include CRISPR-Cas systems. Here, we describe the CRISPR-Cas type II-A system of S. mutans strain P42S, which was found to display natural adaptation and interference activity in response to phage infection and plasmid transformation. Newly acquired spacers were integrated both at the 5′ end of the CRISPR locus and ectopically. In comparisons of the cas genes of P42S to those of other strains of S. mutans, cas1, cas2, and csn2 appear to be highly conserved within the species. However, more diversity was observed with cas9. While the nuclease domains of S. mutans Cas9 (SmCas9) are conserved, the C terminus of the protein, including the protospacer adjacent motif (PAM) recognition domain, is less conserved. In support of these findings, we experimentally demonstrated that the PAMs associated with SmCas9 of strain P42S are NAA and NGAA. These PAMs are different from those previously reported for the CRISPR-Cas system of the model strain S. mutans UA159. This study illustrates the diversity of CRISPR-Cas type II-A systems that can be found within the same bacterial species. IMPORTANCE CRISPR-Cas is one of the mechanisms used by bacteria to defend against viral predation. Increasing our knowledge of the biology and diversity of CRISPR-Cas systems will also improve our understanding of virus-bacterium interactions. As CRISPR-Cas systems acquiring novel immunities under laboratory conditions are rare, Streptococcus mutans strain P42S provides an alternative model to study the adaptation step, which is still the least understood step in CRISPR-Cas biology. Furthermore, the availability of a natural Cas9 protein recognizing an AT-rich PAM opens up new avenues for genome editing purposes.

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Section: Discussioncontrasting

confidence: 72%

Characterization of a Type II-A CRISPR-Cas System in Streptococcus mutans

Mosterd

Moineau

2020

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“…The selection of these mutants suggests taking advantage of different phage resistance mechanisms. For example, some of them may have mutations at the phage receptor level (19) or other host factors (20). However, many of these BIMs are obtained via their CRISPR-Cas systems (21).…”

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confidence: 99%

Novel Genus of Phages Infecting Streptococcus thermophilus: Genomic and Morphological Characterization

Philippe

Levesque

Dion

et al. 2020

Appl Environ Microbiol

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Streptococcus thermophilus is a lactic acid bacterium commonly used for the manufacture of yogurt and specialty cheeses. Virulent phages represent a major risk for milk fermentation processes worldwide, as they can inactivate the added starter bacterial cells, leading to low-quality fermented dairy products. To date, four genetically distinct groups of phages infecting S. thermophilus have been described. Here, we describe a fifth group. Phages P738 and D4446 are virulent siphophages that infect a few industrial strains of S. thermophilus. The genomes of phages P738 and D4446 were sequenced and found to contain 34,037 and 33,656 bp as well as 48 and 46 open reading frames, respectively. Comparative genomic analyses revealed that the two phages are closely related to each other but display very limited similarities to other S. thermophilus phages. In fact, these two novel S. thermophilus phages share similarities with streptococcal phages of nondairy origin, suggesting that they emerged recently in the dairy environment. IMPORTANCE Despite decades of research and adapted antiphage strategies such as CRISPR-Cas systems, virulent phages are still a persistent risk for the milk fermentation industry worldwide, as they can cause manufacturing failures and alter product quality. Phages P738 and D4446 are novel virulent phages that infect the food-grade Gram-positive bacterial species Streptococcus thermophilus. These two related viruses represent a fifth group of S. thermophilus phages, as they are significantly distinct from other known S. thermophilus phages. Both phages share similarities with phages infecting nondairy streptococci, suggesting their recent emergence and probable coexistence in dairy environments. These findings highlight the necessity of phage surveillance programs as the phage population evolves in response to the application of antiphage strategies.

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“…In these experiments, it is clear that the coevolutionary dynamics observed for S. thermophilus and its phage can be attributed to CRISPR-Cas-mediated immunity to the phage. Resistant bacteria only evolve if the CRISPR-Cas system is inactivated by either antisense RNA expression (76) or an anti-CRISPR (acr) gene encoded by the phage (77), with resistance due to mutations in either the receptor or intracellular host genes required for completing the phage life cycle. This system, therefore, corresponds well with the theoretical scenario in Fig.…”

Section: Lytic Phagementioning

confidence: 99%

It is unclear how important CRISPR-Cas systems are for protecting natural populations of bacteria against infections by mobile genetic elements

Westra

Levin

2020

Proc. Natl. Acad. Sci. U.S.A.

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Articles on CRISPR commonly open with some variant of the phrase “these short palindromic repeats and their associated endonucleases (Cas) are an adaptive immune system that exists to protect bacteria and archaea from viruses and infections with other mobile genetic elements.” There is an abundance of genomic data consistent with the hypothesis that CRISPR plays this role in natural populations of bacteria and archaea, and experimental demonstrations with a few species of bacteria and their phage and plasmids show that CRISPR-Cas systems can play this role in vitro. Not at all clear are the ubiquity, magnitude, and nature of the contribution of CRISPR-Cas systems to the ecology and evolution of natural populations of microbes and the strength of selection mediated by different types of phage and plasmids to the evolution and maintenance of CRISPR-Cas systems. In this perspective, with the aid of heuristic mathematical–computer simulation models, we explore the a priori conditions under which exposure to lytic and temperate phage and conjugative plasmids will select for and maintain CRISPR-Cas systems in populations of bacteria and archaea. We review the existing literature addressing these ecological and evolutionary questions and highlight the experimental and other evidence needed to fully understand the conditions responsible for the evolution and maintenance of CRISPR-Cas systems and the contribution of these systems to the ecology and evolution of bacteria, archaea, and the mobile genetic elements that infect them.

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A mutation in the methionine aminopeptidase gene provides phage resistance in Streptococcus thermophilus

Cited by 19 publications

References 56 publications

Characterization of a Type II-A CRISPR-Cas System in Streptococcus mutans

Characterization of a Type II-A CRISPR-Cas System in Streptococcus mutans

Novel Genus of Phages Infecting Streptococcus thermophilus: Genomic and Morphological Characterization

It is unclear how important CRISPR-Cas systems are for protecting natural populations of bacteria against infections by mobile genetic elements

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