CMFI publication elected “DGHM - Paper of the Month"

Authors' comment:

CO2 and bicarbonate are required for carboxylation reactions in central metabolism and biosynthesis of small molecules in almost all bacteria and eukaryotes. Two systems are available for the acquisition of dissolved inorganic carbon supply (DICS): the cytoplasmic localized carbonic anhydrase (CA) and the membrane-bound bicarbonate transporter, MpsAB, which we first described in 2019 in a non-autotrophic bacterium as (membrane potential generating system) in Staphylococcus aureus.

In the pathogenic species S. aureus, there are contradictions in the literature regarding the presence of a CA or MpsAB. Using bioinformatic analysis of 259 completed and 4,590 unfinished S. aureus genomes, as well as molecular biology methods, we clearly demonstrated that S. aureus does not contain CA and that the bicarbonate transporter MpsAB is the only DICS system in this species. This result has far-reaching consequences with regard to a possible therapeutic application of CA inhibitors, since we show here that S. aureus is completely resistant to these CA inhibitors. But the development of inhibitors against the essential MpsAB needs to be pursued.

Sook-Ha Fan, Elisa Liberini, and Friedrich Götz. Staphylococcus aureus Genomes Harbor Only MpsAB-Like Bicarbonate Transporter but Not Carbonic Anhydrase as Dissolved Inorganic Carbon Supply System. Microbiology Spectrum 9(3): e00970-21. (2021) doi: https://doi.org/10.1128/Spectrum.00970-21.

Original abstract of the article:
In recent years, it became apparent that not only autotrophic but also most other bacteria require CO₂ or bicarbonate for growth. Two systems are available for the acquisition of dissolved inorganic carbon supply (DICS): the cytoplasmic localized carbonic anhydrase (CA) and the more recently described bicarbonate transporter MpsAB (membrane potential generating system). In the pathogenic species Staphylococcus aureus, there are contradictions in the literature regarding the presence of a CA or MpsAB. Here, we address these contradictions in detail. We could demonstrate by careful BLASTp analyses with 259 finished and 4,590 unfinished S. aureus genomes that S. aureus does not contain CA and that the bicarbonate transporter MpsAB is the only DICS system in this species. This finding is further supported by two further pieces of evidence: (i) mpsAB deletion mutants in four different S. aureus strains failed to grow under atmospheric air, which should not be the case if they possess CAs, since we have previously shown that both CA and MpsAB can substitute for each other, and (ii) S. aureus is completely resistant to CA inhibitors, whereas Staphylococcus carnosus, which has been shown to have only CA, was inhibited by ethoxyzolamide (EZA). Taken together, we demonstrate beyond doubt that the species S. aureus possesses only the bicarbonate transporter MpsAB as its sole DICS system.