We observed a significantly higher bacterial burden in the nasopharynx of mice given 50% sucrose in their drinking water compared to controls during the first 3 days post infection. This observation was mirrored at later timepoints but was no longer significant as the bacterial burden became more heterogenous in both groups. One limitation of using bioluminescence as a surrogate for bacterial burden is the high detection limit of 104 CFU7. We therefore also used a second measure by assessing nasal shedding of bacteria by direct sampling. A corresponding, but non-significant trend was observed, where increased shedding was observed in the sucrose group.
How sucrose in drinking water increases the bacterial burden in the nasopharynx has not been addressed in this study, however, it may be that the presence of sucrose in the local environment provides optimal growth conditions for the bacteria. Indeed, S. pyogenes relies heavily on sugar fermentation for growth and energy production. Changes in environmental pH resulting from sugar fermentation can also lead to microcolony and biofilm formation, that are beneficial during the initial stages of infection8. Furthermore, sugar metabolism has also been linked to virulence gene regulation through directly affecting the activity of the Mga regulon9. The Mga regulon is a ubiquitous stand-alone regulator of S. pyogenes that influences approximately 10% of the S. pyogenes genome. These effects include regulation of important virulence genes such as emm, fba, sclA, and scpA, as well as those involved in sugar transport and utilisation10.
In our study, the primary bacterial burden was observed in the nose rather than throats of mice. While the nasal-associated lymphoid tissues (NALT) in the mouse are thought to be functionally equivalent to human tonsils11 and may act an important reservoir for bacteria, the location of the NALT in mice, on the posterior side of the palate11, begs to question the direct influence of sucrose at this location. As we noted an increase in energy intake in the sucrose group, we cannot exclude the possibility that our results are not a direct effect of sucrose, but rather a consequence of metabolic adaptions in these mice. This could be addressed in future studies by matching energy intake by pair feeding mice.
Interestingly, while previous research showed that consumption of sugar sweetened beverages was associated with increased risk of ARF6, consumption was not associated with increased risk of S. pyogenes skin and throat infection in humans12. Since our findings support the idea that sugary drinks promote S. pyogenes growth or survival in the nasopharynx, one could speculate that elevated bacterial burden maintained in a carrier state might lead to increased transmission within household members or increased chance of self-reinfection. This idea is supported by a recent classroom transmission study which pointed to ongoing transmission from asymptomatic carriers who are heavy shedders of bacteria13. Further research would be needed to investigate these potential pathways to disease.