Project Description

Cavities are among the most common chronic diseases worldwide, affecting over 2.5 billion people. The kicker? They’re often a sign of deeper imbalance in the mouth.

Description

Cavities remain one of the most common chronic diseases worldwide, affecting billions of people and often signaling deeper microbial imbalance. Our project seeks to address this issue with a living, self-regulating probiotic therapy that can detect and inhibit Streptococcus mutans, the primary cause of tooth decay, while preserving the oral microbiome’s natural balance.

LactoLock is a probiotic-based system built on a quorum-sensing gene circuit within Lactobacillus. The circuit enables the cell to “sense” when S. mutans is present and respond by secreting targeted antimicrobial peptides (AMPs) such as nisin or mutacin-1140. When no harmful bacteria are detected, the system remains inactive, ensuring protection without unnecessary disruption.

By integrating culture & biofilm characterization, vector design, AMP production, and killswitch safety, our design forms a smart probiotic capable of precise, self-regulating biocontrol that prioritizes both efficacy and ecological safety in oral care.

Global burden hero: world map overlayed on tooth silhouette
Global oral health burden: cavities affect over 3.5 billion people worldwide.

Background

Tooth decay persists as a global health burden despite decades of innovation in oral hygiene. Traditional approaches, such as fluoride, antibacterial mouthwashes, and chemical treatments, have reduced disease prevalence, but they also highlight a critical limitation: these methods are non-selective. They target all microbes at once, disrupting beneficial bacterial communities that are vital for maintaining pH stability, nutrient cycling, and immune defense.

The result is a recurring cycle of imbalance. Beneficial species are eliminated alongside pathogens, allowing Streptococcus mutans to recolonize and restart the decay process. This underscores the need for strategies that treat disease without compromising the microbial ecosystem.

Advances in synthetic biology and probiotic engineering now enable a smarter alternative. By designing cells that respond only to harmful signals, we can target pathogens precisely while preserving healthy bacteria. LactoLock builds on this principle by combining quorum-sensing detection with targeted AMP secretion to create a probiotic therapy that adapts intelligently to its environment.

Split: chemical oral care vs probiotic barrier
Traditional oral care focuses on eradication. LactoLock focuses on equilibrium and treats the cause without harming the community.

Rethinking Oral Health: Why This Matters

Conventional oral care products, such as fluoride toothpaste and antiseptic mouthwashes, operate as “always-on” systems. They continuously act on the oral microbiome, killing both harmful and beneficial bacteria alike. While effective at reducing short-term bacterial load, these broad-spectrum methods can disrupt microbial balance and allow opportunistic species like Streptococcus mutans to quickly recolonize after treatment.

Our approach is designed for precision and balance rather than constant chemical action. LactoLock uses a quorum-sensing regulated circuit that detects when S. mutans reaches harmful levels and then triggers antimicrobial peptide (AMP) production only in response. This means the system remains inactive under healthy conditions and selectively active when needed. The goal is to protect the oral microbiome while suppressing the root cause of cavities.

Comparison of always-on and quorum-sensing-controlled oral therapies
Traditional “always-on” oral products act indiscriminately on the microbiome. In contrast, LactoLock’s quorum-sensing system activates only when S. mutans signals are detected, which enables targeted antimicrobial action and microbiome preservation.

Relevancy

Dental care is often neglected, especially in low-income communities with limited access to routine care. Cavities can progress without timely treatment. With LactoLock, we aim to provide an inexpensive and effective option that works with the oral microbiome and supports better oral health in underserved settings.

Communities connected to a central probiotic icon
Who benefits most: equity and access.

What Inspired Us

Our inspiration came from three key observations. First, despite decades of progress in oral hygiene, tooth decay remains one of the most widespread chronic diseases worldwide. Second, current treatments like fluoride and antiseptic rinses act broadly and often disrupt both harmful and beneficial microbes. Third, advances in synthetic biology and quorum-sensing control now make it possible to engineer living systems that can respond only when needed, which provides a smarter and more balanced approach.

By combining these insights, our team envisioned LactoLock, a probiotic solution that leverages engineered genetic circuits to detect and neutralize Streptococcus mutans while maintaining harmony within the oral microbiome. This intersection of clinical need, biological innovation, and systems design is what inspired our project.

How It Works

  1. Sensing: an engineered Lactobacillus detects quorum signals from nearby S. mutans.
  2. Actuation: detection triggers gene expression and AMP secretion. Producer immunity keeps the host safe.
  3. Outcome: AMPs target S. mutans and reduce biofilm clusters while sparing commensals.
  4. Balance: a healthier and more stable oral microbiome forms around the tooth surface.
Four-stage flow: Sensing → Actuation → Outcome → Balance

Why It’s Different & Broader Impacts

Compared to current options
  • Targeted, on-demand AMP expression instead of constant broad antiseptics.
  • Potential persistence between brushings through colonization.
  • Modular design: swap AMPs or sensing logic as evidence evolves.
Risks & mitigations
  • Resistance: AMP cocktails or alternation.
  • Microbiome disruption: specificity testing and gated expression.
  • HGT and containment: chromosomal integration and kill-switch strategies.
Comparison: chemical mouthwash vs living probiotic therapy

Looking Ahead (Future Plans)

Wet Lab
  • Co-culture CFU and biofilm assays (CLSM or crystal violet).
  • Quorum threshold tuning and immunity validation.
Safety & Stability
  • Chromosomal integration and stability studies.
  • Biocontainment (killswitch) prototyping.
Human Practices
  • Stakeholder interviews with dentists, patients, and regulators.
  • Risk and benefit mapping plus ethical considerations.

References

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