The role of cyclic nucleotides in bacterial antimicrobial resistance and tolerance

Nucleotide signalling molecules - mainly cyclic 3',5'-adenosine phosphate (cAMP), bis-(3',5')-cyclic diguanosine monophosphate (c-di-GMP), and bis-(3',5')-cyclic diadenosine monophosphate (c-di-AMP) - contribute to the regulation of cellular pathways. Numerous recent works have focused on the involvement of these cyclic nucleotide phosphates (cNPs) in bacterial resistance and tolerance to antimicrobial treatment. Indeed, the rise of antimicrobial resistance (AMR) is a rising global threat to human health, while the rise of antimicrobial tolerance underlies the development of AMR and long-term infections, placing an additional burden on this problem. Here, we summarise the current understanding of cNP signalling in bacterial physiology with a focus on our understanding of how cNP signalling affects AMR and antimicrobial tolerance in different bacterial species. We also discuss additional cNP-related drug targets in bacterial pathogens that may have therapeutic potential.