Search for bacteriophages of black-pigmented Gram-negative anaerobes from dental plaque

Sandmeier, H.; Bär, K.; Meyer, Jürg

doi:10.1111/j.1574-695x.1993.tb00324.x

Cited by 8 publications

(6 citation statements)

References 2 publications

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“…Therefore, unless there are other, yet unknown cOA synthesis pathways, it seems unlikely these molecules play a critical role in PorX-regulated signalling. Given that the BREX system and recently discovered associated genes including brxU ( 72 ) and brxR ( 73 , 74 ) are also absent in P. gingivalis , it is puzzling that bacteriophages have not yet been shown to infect P. gingivalis , which would indicate the presence of a resistance system ( 75 ). Because cOAs regulate defence systems, it is tempting to speculate that they activate an unknown anti-phage mechanism involving PorX, and this should be investigated in more detail.…”

Section: Discussionmentioning

confidence: 99%

Response regulator PorX coordinates oligonucleotide signalling and gene expression to control the secretion of virulence factors

Schmitz

Madej

Nowakowska

et al. 2022

Nucleic Acids Research

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The PglZ family of proteins belongs to the alkaline phosphatase superfamily, which consists of metallohydrolases with limited sequence identity but similar metal-coordination architectures in otherwise divergent active sites. Proteins with a well-defined PglZ domain are ubiquitous among prokaryotes as essential components of BREX phage defence systems and two-component systems (TCSs). Whereas other members of the alkaline phosphatase superfamily are well characterized, the activity, structure and biological function of PglZ family proteins remain unclear. We therefore investigated the structure and function of PorX, an orphan response regulator of the Porphyromonas gingivalis TCS containing a putative PglZ effector domain. The crystal structure of PorX revealed a canonical receiver domain, a helical bundle, and an unprecedented PglZ domain, similar to the general organization of the phylogenetically related BREX-PglZ proteins. The PglZ domain of PorX features an active site cleft suitable for large substrates. An extensive search for substrates revealed that PorX is a phosphodiesterase that acts on cyclic and linear oligonucleotides, including signalling molecules such as cyclic oligoadenylates. These results, combined with mutagenesis, biophysical and enzymatic analysis, suggest that PorX coordinates oligonucleotide signalling pathways and indirectly regulates gene expression to control the secretion of virulence factors.

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Section: Discussionmentioning

confidence: 99%

Response regulator PorX coordinates oligonucleotide signalling and gene expression to control the secretion of virulence factors

Schmitz

Madej

Nowakowska

et al. 2022

Nucleic Acids Research

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“…Surprisingly, although Pg has been the subject of study for over 40 years [ 19 ], essentially nothing is known of its phages, and the prevailing paradigm is that phages are not important in the ecology of Pg . An early study [ 20 ] using a culture-based approach to uncover prophage interactions in Pg found no evidence of plaque formation (lysis of bacteria in lawns), and though future studies with modified approaches were recommended, there is no evidence they were carried out. More recent studies using comparative genomic analyses of Pg genomes have identified candidate phage genes [ 21 ], and two Pg genomes have been noted as having candidate prophage regions, though these are not further described (ATCC 49417, with a region noted as Bacteriophage phi Pg1 in GenBank record FUFH01000018.1; and WW2952, with a candidate prophage noted as PgSL1 [ 22 ]).…”

Section: Introductionmentioning

confidence: 99%

Phages are unrecognized players in the ecology of the oral pathogen Porphyromonas gingivalis

Matrishin¹,

Haase²,

Dewhirst³

et al. 2023

Microbiome

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Background Porphyromonas gingivalis (hereafter “Pg”) is an oral pathogen that has been hypothesized to act as a keystone driver of inflammation and periodontal disease. Although Pg is most readily recovered from individuals with actively progressing periodontal disease, healthy individuals and those with stable non-progressing disease are also colonized by Pg. Insights into the factors shaping the striking strain-level variation in Pg, and its variable associations with disease, are needed to achieve a more mechanistic understanding of periodontal disease and its progression. One of the key forces often shaping strain-level diversity in microbial communities is infection of bacteria by their viral (phage) predators and symbionts. Surprisingly, although Pg has been the subject of study for over 40 years, essentially nothing is known of its phages, and the prevailing paradigm is that phages are not important in the ecology of Pg. Results Here we systematically addressed the question of whether Pg are infected by phages—and we found that they are. We found that prophages are common in Pg, they are genomically diverse, and they encode genes that have the potential to alter Pg physiology and interactions. We found that phages represent unrecognized targets of the prevalent CRISPR-Cas defense systems in Pg, and that Pg strains encode numerous additional mechanistically diverse candidate anti-phage defense systems. We also found that phages and candidate anti-phage defense system elements together are major contributors to strain-level diversity and the species pangenome of this oral pathogen. Finally, we demonstrate that prophages harbored by a model Pg strain are active in culture, producing extracellular viral particles in broth cultures. Conclusion This work definitively establishes that phages are a major unrecognized force shaping the ecology and intra-species strain-level diversity of the well-studied oral pathogen Pg. The foundational phage sequence datasets and model systems that we establish here add to the rich context of all that is already known about Pg, and point to numerous avenues of future inquiry that promise to shed new light on fundamental features of phage impacts on human health and disease broadly.

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“…Such dynamics would have the potential to limit colonization by new strains of Pg , either at the level of the person or at the level of individual periodontal pockets, as a result of killing by resident Pg phages. Recent work has also shown that in the related gut-associated Bacteroides fragilis , activated prophages are an important mechanism of intra-species antagonism and cross-killing 59 , and in Sandmeier’s search for Pg prophages in 1993 16 he observed antagonism between strains of Pg , though he could not link it to phages. As individuals with Pg often harbor multiple strains of the species, with increasing numbers observed in periodontal disease 69 , the potential for phage-mediated intra-species antagonism also raises the possibility that bursts of disease progression are the result of bouts of phage-mediated cross-killing.…”

Section: Discussionmentioning

confidence: 99%

“…Surprisingly, although Pg has been the subject of study for over 40 years 15 , essentially nothing is known of its phages, and the prevailing paradigm is that phages are not important in the ecology of Pg . An early study 16 using a culture-based approach to uncover prophage interactions in Pg found no evidence of plaque formation (lysis of bacteria in lawns), and though future studies with modified approaches were recommended there is no evidence they were carried out. More recent studies using comparative genomic analyses of Pg genomes have identified candidate phage genes 17 , and two Pg genomes have been noted as having candidate prophage regions, though these are not further described (ATCC 49417, with a region noted as Bacteriophage phi Pg1 in GenBank record FUFH01000018.1; and WW2952, with a candidate prophage noted as PgSL1 18 ).…”

Section: Introductionmentioning

confidence: 99%

Phages are important unrecognized players in the ecology of the oral pathogenPorphyromonas gingivalis

Matrishin¹,

Haase²,

Dewhirst

et al. 2022

Preprint

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Background.Porphyromonas gingivalis(hereafter "Pg") is an oral pathogen that can act as a keystone driver of inflammation and periodontal disease. AlthoughPgis most readily recovered from individuals with actively progressing periodontal disease, healthy individuals and those with stable non-progressing disease are also colonized byPg. Insights into the factors shaping the striking strain-level variation inPg, and its variable associations with disease, are needed to achieve a more mechanistic understanding of periodontal disease and its progression. A key force shaping strain level diversity in all microbial communities is infection of bacteria by their viral (phage) predators and symbionts. Surprisingly, althoughPghas been the subject of study for over 40 years, essentially nothing is known of its phages, and the prevailing paradigm is that phages are not important in the ecology ofPg.Results.Here we systematically addressed the question of whetherPgare infected by phages - and we found that they are. We found that prophages are common inPg, they are genomically diverse, and they encode genes that have the potential to alterPgphysiology and interactions. We found that phages represent unrecognized targets of the prevalent CRISPR-Cas defense systems inPg, and thatPgstrains encode numerous additional mechanistically diverse candidate anti-phage defense systems. We also found that phages and candidate anti-phage defense system elements together are major contributors to strain level diversity and the species pangenome of this oral pathogen. Finally, we demonstrate that prophages harbored by a modelPgstrain are active in culture, producing extracellular viral particles in broth cultures.Discussion.This work definitively establishes that phages are a major unrecognized force shaping the ecology and intraspecies strain-level diversity of the well-studied oral pathogenPg. The foundational phage sequence datasets and model systems that we establish here add to the rich context of all that is already known aboutPg, and point to numerous avenues of future inquiry that promise to shed new light on fundamental features of phage impacts on human health and disease broadly.

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Search for bacteriophages of black-pigmented Gram-negative anaerobes from dental plaque

Cited by 8 publications

References 2 publications

Response regulator PorX coordinates oligonucleotide signalling and gene expression to control the secretion of virulence factors

Response regulator PorX coordinates oligonucleotide signalling and gene expression to control the secretion of virulence factors

Phages are unrecognized players in the ecology of the oral pathogen Porphyromonas gingivalis

Phages are important unrecognized players in the ecology of the oral pathogenPorphyromonas gingivalis

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