Unresolved mystery of cyclic nucleotide second messengers, periplasmic acid phosphatases and bacterial natural competence

We recently characterized the competitive inhibition of cyclic AMP (cAMP) on three periplasmic acid phosphatases, AphA , NadN , and eP4 (Hel ), in Rd KW20. This inhibitory effect is vital for orchestrating the nutritional growth and competence development in KW20. Initially discovered in , the function of AphA remains however obscure. This study investigates the regulation of expression under nutrient starvation conditions. Using transcriptional reporters with truncated promoter sequences, we found that starvations of carbon and phosphate, but not amino acid, stimulated expression through distinct promoter regions. Deletions of or abolished expression, confirming their crucial roles. Conversely, CytR deletion increased expression, suggesting CytR's role as a repressor of expression. Additionally, we extended the study of 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 concentration dependent manner. Collectively, these data imply a complicated connection between nucleotide metabolism, AphA, cyclic purine and pyrimidine nucleotides in bacterial nutrient uptake and natural competence.