Discover how Streptococcus gordonii uses glucosyltransferase phase variation to modify adhesion to teeth surfaces, affecting dental plaque formation and systemic health.
Imagine your tooth surface as a precious territory coveted by millions of microscopic inhabitants. Among the first colonists seeking to claim this space is Streptococcus gordonii, a bacterial pioneer that plays both sides—it's a normal resident of our oral ecosystem but can transform into an opportunistic pathogen when conditions allow 2 . The initial attachment of these bacteria to the thin layer of salivary proteins coating our teeth, called the salivary pellicle, represents one of the most critical steps in the formation of dental plaque 1 6 .
What makes this process particularly fascinating is the molecular machinery bacteria employ to secure their foothold, and perhaps none is more intriguing than the glucosyltransferase (GTF) enzymes that can dramatically change their adhesion properties through a random switch known as "phase variation."
Recent research has uncovered that this random switching modifies the bacterium's ability to stick to tooth-like surfaces in surprising ways that challenge conventional wisdom about bacterial adhesion. The implications extend beyond basic science, potentially influencing future approaches to preventing not just dental plaque but also serious systemic conditions like infective endocarditis, a life-threatening heart infection that oral bacteria can cause when they enter the bloodstream 2 .
Complex biofilm community where S. gordonii acts as a pioneer colonizer
Oral bacteria can cause infective endocarditis when entering bloodstream
Glucosyltransferases (GTFs) are specialized enzymes produced by oral streptococci that build glucans from dietary sugars, particularly sucrose. These glucans act like a molecular glue, helping bacteria adhere to tooth surfaces and to each other, facilitating the development of complex biofilm communities that we know as dental plaque 4 .
What makes S. gordonii's GTF particularly interesting is its capacity for "phase variation"—a random, reversible switch between two distinct phenotypic states: one that produces high levels of GTF activity (Spp+) and another that produces significantly lower levels (Spp-) 4 . This phenomenon represents a bet-hedging strategy for the bacterial population, ensuring that at least some cells are prepared for changing environmental conditions, much like how some people carry both umbrellas and sunglasses on a partly cloudy day.
Phase variation occurs through genetic mechanisms that randomly turn genes on or off, creating subpopulations with different characteristics within the same bacterial strain. This generates diversity without requiring evolutionary timescales, providing immediate adaptability. For S. gordonii, this means some cells are optimized for glucan production while others may excel at direct attachment to salivary pellicles.
Random on/off switching of GTF genes
Creation of Spp+ and Spp- subpopulations
Preparedness for changing environments
In 1992, a landmark study published in Oral Microbiology and Immunology set out to investigate how this phase variation between Spp+ and Spp- phenotypes affected S. gordonii's ability to adhere to saliva-coated surfaces 4 . The researchers designed a series of elegant experiments that would reveal unexpected truths about bacterial adhesion.
The scientists worked with isogenic strains (genetically identical except for the phase variation status) of S. gordonii that had spontaneously switched to either Spp+ or Spp- phenotypes.
They created a laboratory model of tooth enamel by using hydroxyapatite (HA), the primary mineral component of teeth. Some HA beads were coated with human saliva to create saliva-coated hydroxyapatite (S-HA), mimicking the natural pellicle on teeth, while others were left uncoated.
The researchers measured bacterial adhesion using a washed-cell adhesion test. They standardized the number of bacterial cells and allowed them to interact with the HA or S-HA surfaces for a specific time period under controlled conditions.
The experiments were conducted both with and without sucrose present to determine whether the sugar source influenced adhesion capabilities differently for the two phenotypes.
Since cell surface hydrophobicity often correlates with adhesion ability, the team also compared this property between Spp+ and Spp- variants to determine if observed adhesion differences could be explained by surface chemistry changes.
The findings contradicted what many researchers expected:
| Property | Spp+ (High GTF) | Spp- (Low GTF) |
|---|---|---|
| GTF Activity | High (5x higher than Spp-) | Low |
| Adhesion to S-HA | Lower | Significantly Higher |
| Adhesion to Plain HA | Similar to Spp- | Similar to Spp+ |
| Response to Sucrose on HA | Increased adhesion | Increased adhesion |
| Response to Sucrose on S-HA | No effect | No effect |
| Cell Surface Hydrophobicity | No correlation with adhesion | No correlation with adhesion |
The most striking discovery was that the Spp- variants, despite producing considerably less glucosyltransferase enzyme, adhered much more effectively to saliva-coated hydroxyapatite than their Spp+ counterparts 4 . This finding directly challenged the prevailing assumption that higher GTF activity would naturally lead to better adhesion.
Even more surprisingly, sucrose increased adhesion to plain HA surfaces for both variants but had no significant effect on their attachment to saliva-coated surfaces 4 . This suggested that the presence of the salivary pellicle fundamentally changed the adhesion mechanism. The researchers noted that this effect wasn't unique to sucrose—other carbohydrates and even sodium chloride produced similar results, indicating this might be a general ionic strength effect rather than a sucrose-specific phenomenon 4 .
| Surface Type | Effect of Sucrose on Spp+ | Effect of Sucrose on Spp- |
|---|---|---|
| Plain HA | Increased adhesion | Increased adhesion |
| Saliva-Coated HA | No significant effect | No significant effect |
Most intriguingly, the research team concluded that the phase variation process must affect additional bacterial properties beyond just GTF production—other changes "relevant to adhesion" were clearly occurring, though their exact nature remained to be discovered 4 .
While the glucosyltransferase phase variation represents a fascinating adaptation, it's just one piece of the adhesion puzzle for S. gordonii. Research has revealed that this bacterium employs a diverse arsenal of adhesins—specialized surface proteins that recognize and bind to specific receptors—each contributing to its ability to colonize different surfaces and tissues.
| Adhesin | Type/Function | Binding Targets |
|---|---|---|
| Hsa | Serine-rich repeat adhesin | Sialic acid on salivary glycoproteins, platelets 1 6 |
| GspB | Serine-rich repeat adhesin | Sialic acid residues on platelet GPIbα 8 |
| SspA/SspB | Antigen I/II family polypeptides | β1 integrins on epithelial cells 3 |
| CshA | Fibrillar adhesin | Fibronectin, multiple host molecules 5 |
| AbpA | Amylase-binding protein | Salivary amylase 7 |
| Ash1/Ash2 | Novel adhesins | Sialidase-treated erythrocytes (sialic acid-independent) 6 |
This impressive adhesion repertoire allows S. gordonii to interact with diverse surfaces—from salivary pellicles on teeth to heart valves—explaining its dual nature as both a commensal oral inhabitant and a potential pathogen 2 .
The serine-rich repeat adhesins like Hsa and GspB deserve special attention. These sialic-acid binding proteins not only facilitate attachment to teeth and platelets but also play a significant role in immune recognition.
A 2017 study demonstrated that S. gordonii's SRR adhesins contribute significantly to the maturation and activation of human dendritic cells—key sentinels of our immune system . When researchers compared wild-type bacteria to mutant strains lacking Hsa or GspB, they found the adhesin-deficient mutants bound much more poorly to dendritic cells and triggered weaker immune responses . This suggests these adhesins do more than just mediate physical attachment—they actively shape the host's immune reaction to the bacterium.
The CshA fibrillar adhesin represents another marvel of bacterial engineering. Research published in the Journal of Biological Chemistry revealed that CshA employs a sophisticated "catch-clamp" mechanism for binding fibronectin 5 .
The adhesin's N-terminal region acts as a disordered domain that first "catches" the fibronectin molecule, forming a rapidly assembled but easily dissociated pre-complex. This then allows a neighboring ligand-binding domain to tightly "clamp" the two molecules together in a stable embrace 5 . This two-step process combines flexibility with strength, optimizing bacterial attachment under dynamic physiological conditions.
The discovery that S. gordonii's glucosyltransferase phase variation modifies adhesion in unexpected ways—with low-GTF variants actually adhering better to salivary pellicles—has reshaped our understanding of early dental plaque formation. It suggests that bacterial diversity generated through phase variation may be more important than previously appreciated, with different subpopulations potentially playing distinct roles in biofilm development.
From a clinical perspective, understanding these adhesion mechanisms opens possibilities for novel anti-adhesive therapies that could disrupt the initial attachment of pioneer bacteria like S. gordonii, potentially preventing not just plaque formation but also subsequent serious conditions like infective endocarditis 2 5 .
The finding that SRR adhesin function can be blocked by molecules like 3'-sialyllactose suggests that specific receptor analogs might one day be used to interfere with harmful bacterial colonization without indiscriminately killing our microbial flora.
As we continue to unravel the complexities of S. gordonii's adhesion strategies, we gain not only fundamental insights into microbial ecology but also potential avenues for manipulating these interactions to improve human health. The humble bacterial switch between Spp+ and Spp- states reminds us that in microbiology, as in life, apparent weaknesses can sometimes be hidden strengths, and the most obvious explanations often conceal surprising truths.
| Research Tool | Function in Adhesion Studies |
|---|---|
| Hydroxyapatite (HA) Beads | Mimics tooth mineral surface for adhesion assays 4 |
| Saliva-Coated Hydroxyapatite (S-HA) | Represents the natural salivary pellicle on teeth 1 4 |
| Isogenic Bacterial Strains | Genetically identical except for specific traits (e.g., Spp+/Spp-), allowing fair comparison 4 |
| Recombinant Adhesin Proteins | Purified adhesion molecules for studying binding mechanisms 5 |
| Lactococcus lactis Expression System | Non-adherent bacterium used to express individual S. gordonii adhesins, simplifying functional studies 5 |
| 3'-Sialyllactose | SRR adhesin inhibitor used to block bacterial binding to host cells |
| Flow Cell Biofilm Models | Allows real-time observation of biofilm development under controlled conditions 7 |