title: Streptococcus pyogenes c-di-AMP phosphodiesterase, GdpP, influences SpeB processing and virulence.
abstract: Small cyclic nucleotide derivatives are employed as second messengers by both prokaryotes and eukaryotes to regulate diverse cellular processes responding to various signals. In bacteria, c-di-AMP has been discovered most recently, and some Gram-positive pathogens including S. pyogenes use this cyclic nucleotide derivative as a second messenger instead of c-di-GMP, a well-studied important bacterial second messenger. GdpP, c-di-AMP phosphodiesterase, is responsible for degrading c-di-AMP inside cells, and the cellular role of GdpP in S. pyogenes has not been examined yet. To test the cellular role of GdpP, we created a strain with a nonpolar inframe deletion of the gdpP gene, and examined the properties of the strain including virulence. From this study, we demonstrated that GdpP influences the biogenesis of SpeB, the major secreted cysteine protease, at a post-translational level, susceptibility to the beta lactam antibiotic ampicillin, and is necessary for full virulence in a murine subcutaneous infection model.
authors.affiliation: Department of Microbiology, Southern Illinois University, Carbondale, Illinois, USA. kyuhongcho@gmail.com
authors.forename: Kyu Hong
authors.initials: KH
authors.lastname: Cho
authors.forename: Song Ok
authors.initials: SO
authors.lastname: Kang
mesh_terms: D000667:Ampicillin / Q000494:pharmacology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000378:metabolism*; D015226:Dinucleoside Phosphates / Q000378:metabolism*; D024881:Drug Resistance, Bacterial; D005098:Exotoxins / Q000378:metabolism*; D017353:Gene Deletion; D051379:Mice; D008812:Mice, Hairless; D008826:Microbial Sensitivity Tests; D010727:Phosphoric Diester Hydrolases / Q000502:physiology*; D013297:Streptococcus pyogenes / Q000201:enzymology* / Q000378:metabolism / Q000821:virology; D014774:Virulence
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D015226:Dinucleoside Phosphates; D005098:Exotoxins; C528998:cyclic diadenosine phosphate; C027951:erythrogenic toxin; D000667:Ampicillin; D010727:Phosphoric Diester Hydrolases