The Two-Component System 09 Regulates Pneumococcal Carbohydrate Metabolism and Capsule Expression.

two-component regulatory systems (TCSs) are important systems that perceive and respond to various host environmental stimuli. In this study, we have explored the role of TCS09 on gene expression and phenotypic alterations in D39. Our comparative transcriptomic analyses identified 67 differently expressed genes in total. Among those, and the operon involved in galactose metabolism showed the highest changes. Intriguingly, the encapsulated and nonencapsulated -mutants showed significant growth defects under nutrient-defined conditions, in particular with galactose as a carbon source. Phenotypic analyses revealed alterations in the morphology of the nonencapsulated - and -mutants, whereas the encapsulated - and -mutants produced higher amounts of capsule. Interestingly, the encapsulated D39∆ showed only the opaque colony morphology, while the D39∆- and D39∆-mutants had a higher proportion of transparent variants. The phenotypic variations of D39ΔΔ and D39ΔΔ are in accordance with their higher numbers of outer membrane vesicles, higher sensitivity against Triton X-100 induced autolysis, and lower resistance against oxidative stress. In conclusion, these results indicate the importance of TCS09 for pneumococcal metabolic fitness and resistance against oxidative stress by regulating the carbohydrate metabolism and thereby, most likely indirectly, the cell wall integrity and amount of capsular polysaccharide.