Biology and Genome Sequence of Streptococcus mutans Phage M102AD

Delisle, Allan L.; Guo, Mingke; Chalmers, Natalia I.; Barcak, Gerard J.; Rousseau, Geneviève M.; Moineau, Sylvain

doi:10.1128/aem.07726-11

Cited by 26 publications

(50 citation statements)

References 47 publications

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“…Toward this end, S. mutans has long been viewed as an ideal target for lysin therapy because of its causal relationship to dental caries. However, despite the isolation of multiple S. mutans phages (35), their reported lytic activity on S. mutans biofilms (36), and sequencing of their genomes (37), no lysin active against S. mutans had been reported until our group created ClyR, a chimeric lysin, in 2015 (22).…”

Section: Discussionmentioning

confidence: 99%

Antibiofilm Activities of a Novel Chimeolysin against Streptococcus mutans under Physiological and Cariogenic Conditions

Yang

Shang

et al. 2016

Antimicrob Agents Chemother

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dStreptococcus mutans often survives as a biofilm on the tooth surface and contributes to the development of dental caries. We investigated the efficacy of ClyR, an engineered chimeolysin, against S. mutans biofilms under physiological and cariogenic conditions. Susceptibility tests showed that ClyR was active against all clinical S. mutans isolates tested as well as S. mutans biofilms that displayed resistance to penicillin. The S. mutans biofilms that formed on hydroxyapatite discs under physiological sugar conditions and cariogenic conditions were reduced ϳ2 logs and 3 logs after treatment with 100 g/ml ClyR, respectively. In comparison, only a 1-log reduction was observed in the chlorhexidine gluconate (ChX)-treated group, and no killing effect was observed in the NaF-treated group. A mouse dental colonization model showed that repeated use of ClyR for 3 weeks (5 g/day) reduced the number of colonized S. mutans cells in the dental plaques significantly (P < 0.05) and had no harmful effects on the mice. Furthermore, toxicity was not noted at concentrations exceeding those used for the in vitro and in vivo studies, and ClyRspecific antibodies could not be detected in mouse saliva after repeated use of ClyR in the oral cavity. Our data collectively demonstrate that ClyR is active against S. mutans biofilms both in vitro and in vivo, thus representing a preventative or therapeutic agent for use against dental caries.

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Section: Discussionmentioning

confidence: 99%

Antibiofilm Activities of a Novel Chimeolysin against Streptococcus mutans under Physiological and Cariogenic Conditions

Yang

Shang

et al. 2016

Antimicrob Agents Chemother

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“…One reason for the limited number of isolated oral phages is likely the narrow host range of phages. For example, Streptococcus mutans phage M102AD only infects serotype c strains (11). Meanwhile, next-generation sequencing data revealed that most oral phages are lysogenic (5,10).…”

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confidence: 99%

A Linear Plasmid-Like Prophage of Actinomyces odontolyticus Promotes Biofilm Assembly

Shen

Yang

Shen

et al. 2018

Appl Environ Microbiol

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The human oral cavity is home to a large number of bacteria and bacteriophages (phages). However, the biology of oral phages as members of the human microbiome is not well understood. Recently, we isolated subsp. strain XH001 from the human oral cavity, and genomic analysis revealed the presence of an intact prophage named xhp1. Here, we demonstrated that xhp1 is a linear plasmid-like prophage, which is a newly identified phage of The prophage xhp1 genome is a 35-kb linear double-stranded DNA with 10-bp single-stranded, 3' cohesive ends. xhp1 exists extrachromosomally, with an estimated copy number of 5. Annotation of xhp1 revealed 54 open reading frames, while phylogenetic analysis suggests that it has limited similarity with other phages. xhp1 phage particles can be induced by mitomycin C and belong to the family, according to transmission electron microscopic examination. The released xhp1 particles can reinfect the xhp1-cured XH001 strain and result in tiny blurry plaques. Moreover, xhp1 promotes XH001 biofilm formation through spontaneous induction and the release of host extracellular DNA (eDNA). In conclusion, we identified a linear plasmid-like prophage of , which enhances bacterial host biofilm assembly and could be beneficial to the host for its persistence in the oral cavity. The biology of phages as members of the human oral microbiome is understudied. Here, we report the characterization of xhp1, a novel linear plasmid-like prophage identified from a human oral isolate, subsp. strain XH001. xhp1 can be induced and reinfect xhp1-cured XH001. The spontaneous induction of xhp1 leads to the lysis of a subpopulation of bacterial hosts and the release of eDNA that promotes biofilm assembly, thus potentially contributing to the persistence of within the oral cavity.

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“…In Streptococcus mutans, one of the primary pathogens implicated in dental caries, relatively little is known about its virulent phages (43,44). Only five phages, designated M101, M102AD, M102, e10, and f1, have been shown to have lytic activity against S. mutans strains of serotypes c, e, and f, respectively (44,45).…”

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confidence: 99%

“…Only five phages, designated M101, M102AD, M102, e10, and f1, have been shown to have lytic activity against S. mutans strains of serotypes c, e, and f, respectively (44,45). Except for S. mutans strain OMZ381, all S. mutans serotype c strains, including UA159, are known to be resistant to phage infection by M102; only strain OMZ381 showed sensitivity to phage infection, resulting in cell lysis (45).…”

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confidence: 99%

Role of the Streptococcus mutans CRISPR-Cas Systems in Immunity and Cell Physiology

et al. 2015

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b CRISPR-Cas systems provide adaptive microbial immunity against invading viruses and plasmids. The cariogenic bacterium Streptococcus mutans UA159 has two CRISPR-Cas systems: CRISPR1 (type II-A) and CRISPR2 (type I-C) with several spacers from both CRISPR cassettes matching sequences of phage M102 or genomic sequences of other S. mutans. The deletion of the cas genes of CRISPR1 (⌬C1S), CRISPR2 (⌬C2E), or both CRISPR1؉2 (⌬C1SC2E) or the removal of spacers 2 and 3 (⌬CR1SP13E) in S. mutans UA159 did not affect phage sensitivity when challenged with virulent phage M102. Using plasmid transformation experiments, we demonstrated that the CRISPR1-Cas system inhibits transformation of S. mutans by the plasmids matching the spacers 2 and 3. Functional analysis of the cas deletion mutants revealed that in addition to a role in plasmid targeting, both CRISPR systems also contribute to the regulation of bacterial physiology in S. mutans. Compared to wild-type cells, the ⌬C1S strain displayed diminished growth under cell membrane and oxidative stress, enhanced growth under low pH, and had reduced survival under heat shock and DNA-damaging conditions, whereas the ⌬C2E strain exhibited increased sensitivity to heat shock. Transcriptional analysis revealed that the two-component signal transduction system VicR/K differentially modulates expression of cas genes within CRISPR-Cas systems, suggesting that VicR/K might coordinate the expression of two CRISPR-Cas systems. Collectively, we provide in vivo evidence that the type II-A CRISPR-Cas system of S. mutans may be targeted to manipulate its stress response and to influence the host to control the uptake and dissemination of antibiotic resistance genes.

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Biology and Genome Sequence of Streptococcus mutans Phage M102AD

Cited by 26 publications

References 47 publications

Antibiofilm Activities of a Novel Chimeolysin against Streptococcus mutans under Physiological and Cariogenic Conditions

Antibiofilm Activities of a Novel Chimeolysin against Streptococcus mutans under Physiological and Cariogenic Conditions

A Linear Plasmid-Like Prophage of Actinomyces odontolyticus Promotes Biofilm Assembly

Role of the Streptococcus mutans CRISPR-Cas Systems in Immunity and Cell Physiology

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