UCSF

Background: Zinc is widely used in oral care products due to its antimicrobial and anti-biofilm properties; however, the molecular mechanisms by which zinc influences Streptococcus mutans (S. mutans) physiology remain incompletely understood. The AdcABC system is the primary high-affinity zinc transporter in S. mutans. We investigated whether loss of adcBC is associated with altered physiological responses in S. mutans. Material and methods: Wild-type (WT), ΔadcBC mutant, and complemented S. mutans UA159 strains were evaluated under zinc-replete and zinc-limited conditions using zinc sulphate (ZnSO₄) at defined concentrations. Growth, carbohydrate utilization, acidogenicity, acid tolerance, aggregation, biofilm formation, and expression of stress response and regulatory genes were assessed. Results: Loss of adcBC impaired growth and reduced utilization of multiple carbohydrates, including key glycolytic substrates, indicating altered metabolism. Zinc supplementation restored growth but did not consistently recover redox-based metabolic activity. Expression of pflA, associated with fermentative metabolism, was reduced in the mutant. Acid tolerance was unaffected by AdcBC. Zinc enhanced aggregation and surface attachment independently of AdcBC, whereas biofilm biomass showed partial dependence on AdcBC-mediated zinc uptake. The ΔadcBC mutant also exhibited altered expression of genes involved in oxidative stress, metal homeostasis, and regulatory pathways. Conclusion: Loss of adcBC is associated with altered physiological responses in S. mutans. Zinc influences bacterial physiology through both uptake-dependent and uptake-independent mechanisms, highlighting its context-dependent role in oral environments.