CO2 chemosensing via cyclic AMP in medically relevant microorganisms
Pathogens sense the 150 fold difference in CO2 via their bicarbonate-regulated sAC-like ACsAC is most closely related to adenylyl cyclases from (cyano)bacteria and unicellular eukaryotes, and regulation by bicarbonate ions is also conserved in these evolutionarily ancient cyclases. Our laboratory studies the role of CO2, bicarbonate, pH sensing via modulation of the cAMP pathway in a number of medically relevant micro-organisms. Upon entering a human being, disease-causing microorganisms initiate a new genetic program, which is usually essential for them to be pathogenic. We found that one of the most potent signals used by invading pathogens is the 150 fold difference in CO2 concentration between air and inside the human body, and we discovered that microorganisms sense this difference via their bicarbonate-regulated sAC-like adenylyl cyclases. We are attempting to develop novel anti-infective therapeutics by blocking this CO2 chemosensing mechanism.
