cCMP and cUMP stimulate the acid phosphatase activity of AphA inHaemophilus influenzae

We recently detailed the competitive inhibition of cyclic AMP (cAMP) on three periplasmic enzymes, AphA, NadN, and Hel, in Haemophilus influenzae Rd KW20. This inhibitory effect is vital for orchestrating the nutritional growth and competence development in KW20. Here, we extended the study to the three other second messengers, i.e., cyclic GMP, cyclic UMP, and cyclic CMP, each sharing structural similarities with cAMP. Notably, cGMP competitively inhibits AphA’s acid phosphatase activity akin to cAMP. In contrast, both cUMP and cCMP stimulate AphA’s phosphatase activity in a dose-dependent manner. This novel finding underscores the intriguing opposing effects of cyclic purine and pyrimidine nucleotides on AphA, suggesting potential intricate biological crosstalk among these second messengers.