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Updated: Jun 13, 2025
Porphyromonas gingivalis as a Model Organism for Assessing Interaction of Anaerobic Bacteria with Host Cells
Published on: December 17, 2015
Phage-based biocontrol of Porphyromonas gingivalis through indirect targeting
Chuncheng Wu1, Jumpei Fujiki2, Jacques Mathieu1
1Department of Civil and Environmental Engineering, Rice University, Houston, Texas, USA.
Abstract:
Bacteriophages offer an opportunity for chemical-free, precise control of problematic bacteria, but this approach can be limited when lytic phages are difficult to obtain for the target host. In such cases, phage-based targeting of cooperating or cross-feeding bacteria (e.g., Streptococcus gordonii) can be an effective approach to control the problematic bacteria (e.g., Porphyromonas gingivalis). Using a dual-species biofilm system, phage predation of S. gordonii (108 PFU·mL-1) decreased the abundance of pathogenic P. gingivalis by >99% compared with no-treatment controls, while also inhibiting the production of cytotoxic metabolic end products (butyric and propionic acids). Phage treatment upregulated genes associated with interspecies co-adhesion (5- to 8-fold) and quorum sensing (10-fold) in residual P. gingivalis, which is conducive to increased potential to bind to S. gordonii. Counterintuitively, lower-titer phage applications (104 PFU·mL-1) increased the production of extracellular polymeric substance (EPS) by 22% and biofilm biomass by 50%. This overproduction of EPS may contribute to the phenomenon where the biofilm separated into two distinct species layers, as observed by confocal laser scanning microscopy. Although more complex mixed-culture systems should be considered to delineate the merits and limitations of this novel biocontrol approach (which would likely require the use of phage cocktails), our results offer proof of concept that indirect phage-based targeting can expand the applicability of phage-based control of pathogenic bacteria for public health protection.
Importance:
Lytic phages are valuable agents for targeted elimination of bacteria in diverse applications. Nevertheless, lytic phages are difficult to isolate for some target pathogens. We offer proof of concept that this limitation may be overcome via indirect phage targeting, which involves knocking out species that interact closely with and benefit the primary problematic target bacteria. Our target (P. gingivalis) only forms a periodontal pathogenic biofilm if the pioneer colonizer (S. gordonii) offers its surface for P. gingivalis to attach. Phage predation of the co-adhesive S. gordonii significantly reduced abundance of the target pathogen by >99%, decreased the total biofilm biomass by >44%, and suppressed its production of cytotoxic metabolic byproducts. Thus, this research extends the scope of phage-based biocontrol for public health protection.
Insights
Bacteriophages can control harmful bacteria like Porphyromonas gingivalis by targeting beneficial bacteria such as Streptococcus gordonii. This indirect phage therapy significantly reduces pathogen levels and harmful byproducts, offering a novel biocontrol strategy.
Area of Science:
- Microbiology and Biotechnology
- Bacteriophage Therapy
- Biofilm Control
Background:
- Bacteriophages (phages) offer precise, chemical-free bacterial control but are limited when lytic phages for target pathogens are unavailable.
- Pathogenic bacteria like Porphyromonas gingivalis often rely on synergistic interactions with other species, such as Streptococcus gordonii, for biofilm formation.
Purpose of the Study:
- To demonstrate the proof of concept for indirect phage targeting as a method to control problematic bacteria.
- To investigate the efficacy of phage predation on Streptococcus gordonii to reduce Porphyromonas gingivalis abundance and pathogenicity in a dual-species biofilm.
Main Methods:
- Utilized a dual-species biofilm model involving Porphyromonas gingivalis and Streptococcus gordonii.
- Applied bacteriophages targeting Streptococcus gordonii at high (10^8 PFU·mL^-1) and low (10^4 PFU·mL^-1) titers.
- Quantified P. gingivalis abundance, measured cytotoxic metabolic end products, analyzed gene expression (co-adhesion, quorum sensing), and assessed biofilm biomass and extracellular polymeric substance (EPS) production.
Main Results:
- High-titer phage predation of S. gordonii reduced P. gingivalis abundance by >99% and inhibited cytotoxic acid production.
- Phage treatment upregulated genes related to interspecies co-adhesion and quorum sensing in residual P. gingivalis.
- Low-titer phage application paradoxically increased EPS production by 22% and biofilm biomass by 50%, leading to biofilm stratification.
Conclusions:
- Indirect phage targeting of cooperating bacteria is a viable strategy to control difficult-to-target pathogens like P. gingivalis.
- This approach expands the applicability of phage-based biocontrol for public health, particularly in managing polymicrobial infections.
- Further research in complex mixed-culture systems using phage cocktails is warranted to optimize this novel biocontrol method.
