Comparing the cariogenic species<i>Streptococcus sobrinus</i>and<i>S. mutans</i>on whole genome level

Conrads, Georg; Soet, Hans J. de; Song, Lifu; Henne, Karsten; Sztajer, Helena; Wagner‐Döbler, Irene; Zeng, An‐Ping

doi:10.3402/jom.v6.26189

Cited by 87 publications

(75 citation statements)

References 80 publications

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“…S. mutans is the predominant causative agent of dental caries (Loesche, 1986; Metwalli et al, 2013), while S. sobrinus has also been implicated in its causation, albeit to a lesser extent than S. mutans (Conrads et al, 2014). Synergistic effects were obtained when PsVP-10 was combined with chlorhexidine, whereas partial synergistic/additive effects were apparent with PsVP-10-triclosan combinations in the study by Lobos et al (2009).…”

Section: Effects Of Antimicrobial Combinations Involving Bacteriocinsmentioning

confidence: 99%

Bacteriocin-Antimicrobial Synergy: A Medical and Food Perspective

et al. 2017

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The continuing emergence of multi-drug resistant pathogens has sparked an interest in seeking alternative therapeutic options. Antimicrobial combinatorial therapy is one such avenue. A number of studies have been conducted, involving combinations of bacteriocins with other antimicrobials, to circumvent the development of antimicrobial resistance and/or increase antimicrobial potency. Such bacteriocin-antimicrobial combinations could have tremendous value, in terms of reducing the likelihood of resistance development due to the involvement of two distinct mechanisms of antimicrobial action. Furthermore, antimicrobial synergistic interactions may also have potential financial implications in terms of decreasing the costs of treatment by reducing the concentration of an expensive antimicrobial and utilizing it in combination with an inexpensive one. In addition, combinatorial therapies with bacteriocins can broaden antimicrobial spectra and/or result in a reduction in the concentration of an antibiotic required for effective treatments to the extent that potentially toxic or adverse side effects can be reduced or eliminated. Here, we review studies in which bacteriocins were found to be effective in combination with other antimicrobials, with a view to targeting clinical and/or food-borne pathogens. Furthermore, we discuss some of the bottlenecks which are currently hindering the development of bacteriocins as viable therapeutic options, as well as addressing the need to exercise caution when attempting to predict clinical outcomes of bacteriocin-antimicrobial combinations.

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Section: Effects Of Antimicrobial Combinations Involving Bacteriocinsmentioning

confidence: 99%

Bacteriocin-Antimicrobial Synergy: A Medical and Food Perspective

et al. 2017

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“…Previous studies have searched for ComDE and ComRS systems in S. sobrinus [14,17]. Although some homologs of genes in the S. mutans ComDE or ComRS pathways were found in S. sobrinus, the pathways were largely incomplete and thought to be nonfunctional.…”

Section: Resultsmentioning

confidence: 99%

“…Both the ComRS and ComDE systems activate the sigma factor ComX and other subsequent competence genes. S. mutans has functional ComDE and ComRS pathways, but genomic studies predict that both pathways are missing or incomplete in S. sobrinus [14,17]. It is unclear how S. sobrinus can form communities and infect humans without a functional competence pathway.…”

Section: Introductionmentioning

confidence: 99%

A ComRS competence pathway in the oral pathogen Streptococcus sobrinus

Wyllie

Jensen

2020

Preprint

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Streptococcus sobrinus is one of two species of bacteria that cause dental caries (tooth decay) in humans. Our knowledge of S. sobrinus is limited despite the organism's important role in oral health. It is widely believed that S. sobrinus lacks the natural competence pathways that are used by other streptococci to regulate growth, virulence, and quorum sensing. The lack of natural competence has also prevented genetic manipulation of S. sobrinus, limiting our knowledge of its pathogenicity.We discovered a functional ComRS competence system in S. sobrinus. The ComRS pathway in S. sobrinus has a unique structure, including two copies of the transcriptional regulator ComR and a peptide pheromone (XIP) that lacks aromatic amino acids. We show that synthetic XIP allows transformation of S. sobrinus with plasmid or linear DNA, and we leverage this newfound genetic tractability to confirm that only one of the ComR homologs is required for induced competence.Although S. sobrinus is typically placed among the mutans group streptococci, the S. sobrinus ComRS system is structurally and functionally similar to the competence pathways in the salivarius group. Like S. salivarius, the ComRS gene cluster in S. sobrinus includes a peptide cleavage/export gene, and the ComRS system appears coupled to a bacteriocin response system. These findings raise questions about the true phylogenetic placement of S. sobrinus.Finally, we identified two strains of S. sobrinus appear to be "cheaters" by either not responding to or not producing XIP. While the mechanisms of cheating could be independent, we show how a recombination event in the non-responsive strain would restore function of the ComRS pathway but delete the gene encoding XIP. Thus the S. sobrinus ComRS pathway provides a lens into the evolution of ecological cheaters.

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“…Both cariogenic bacteria are equally virulent with regard to dental caries (Conrads et al ). However, Strep mutans is more frequently isolated from the oral cavity (Loesche ) and it is first to adhere to teeth through adhesins such as Ag I/II.…”

Section: Virulence Properties Of Strep Mutans and The Targets For Vamentioning

confidence: 99%

Dental caries vaccine: are we there yet?

Patel

2020

Letters in Applied Microbiology

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Dental caries, caused by Streptococcus mutans, is a common infection. Caries vaccine has been under investigation for the last 40 years. Many in vitro and in vivo studies and some human clinical trials have determined many pertinent aspects regarding vaccine development. The virulence determinants of Strep. mutans, such as Ag I/II, responsible for adherence to surfaces, glucosyltransferase, responsible for the production of glucan, and the glucan‐binding protein, responsible for the attachment of glucan to surfaces, have been known to elicit an antigen‐specific immune response. It is also known that more than one antigen or a functional part of the genome responsible for these virulence determinants provide a better host response compared with the monogenic vaccine or complete genome of a specific antigen. To enhance the host response, the use of adjuvants has been studied and the routes of antigen administration have been investigated. In recent years, some promising vaccines such as pGJA‐P/VAX, LT derivative/Pi39‐512, KFD2‐rPAc and SBR/GBR‐CMV‐nirB have been developed and tested in animals. New virulence targets need to be explored. Multicentre collaborative studies and human clinical trials are required and some interest from funders and public health experts should be generated to overcome this hurdle. Significance and Impact of the Study Dental caries is an irreversible, multifactorial opportunistic infection. The treatment is costly, making it a public health problem. Despite many years of promising laboratory research, animal studies and clinical trials, there is no commercially available vaccine today. The research objectives have become more refined from lessons learnt over the years. Multigenic DNA/recombinant vaccines, using the best proved adjuvants with a delivery system for the nasal or sublingual route, should be developed and researched with multicentre collaborative efforts. In addition, new vaccine targets can be identified. To overcome the economic hurdle, funders and public health interest should be stimulated.

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Comparing the cariogenic speciesStreptococcus sobrinusandS. mutanson whole genome level

Cited by 87 publications

References 80 publications

Bacteriocin-Antimicrobial Synergy: A Medical and Food Perspective

Bacteriocin-Antimicrobial Synergy: A Medical and Food Perspective

A ComRS competence pathway in the oral pathogen Streptococcus sobrinus

Dental caries vaccine: are we there yet?

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