| Online-Ressource |
Verfasst von: | Eisenberg, Philip [VerfasserIn]  |
| Albert, Leon [VerfasserIn]  |
| Teuffel, Jonathan [VerfasserIn]  |
| Zitzow, Eric [VerfasserIn]  |
| Michaelis, Claudia [VerfasserIn]  |
| Jarick, Jane [VerfasserIn]  |
| Sehlke, Clemens [VerfasserIn]  |
| Große, Lisa [VerfasserIn]  |
| Bader, Nicole [VerfasserIn]  |
| Nunes-Alves, Ariane [VerfasserIn]  |
| Kreikemeyer, Bernd [VerfasserIn]  |
| Schindelin, Hermann [VerfasserIn]  |
| Wade, Rebecca C. [VerfasserIn]  |
| Fiedler, Tomas [VerfasserIn]  |
Titel: | The non-phosphorylating glyceraldehyde-3-phosphate dehydrogenase GapN is a potential new drug target in Streptococcus pyogenes |
Verf.angabe: | Philip Eisenberg, Leon Albert, Jonathan Teuffel, Eric Zitzow, Claudia Michaelis, Jane Jarick, Clemens Sehlke, Lisa Große, Nicole Bader, Ariane Nunes-Alves, Bernd Kreikemeyer, Hermann Schindelin, Rebecca C. Wade and Tomas Fiedler |
E-Jahr: | 2022 |
Jahr: | 15 February 2022 |
Umfang: | 18 S. |
Fussnoten: | Gesehen am 05.04.2022 |
Titel Quelle: | Enthalten in: Frontiers in microbiology |
Ort Quelle: | Lausanne : Frontiers Media, 2010 |
Jahr Quelle: | 2022 |
Band/Heft Quelle: | 13(2022), Artikel-ID 802427, Seite 1-18 |
ISSN Quelle: | 1664-302X |
Abstract: | The strict human pathogen Streptococcus pyogenes causes infections of varying severity, ranging from self-limiting suppurative infections to life-threatening diseases like necrotizing fasciitis or streptococcal toxic shock syndrome. Here, we show that the non-phosphorylating glyceraldehyde-3-phosphate dehydrogenase GapN is an essential enzyme for S. pyogenes. GapN converts glyceraldehyde 3-phosphate into 3-phosphoglycerate coupled to the reduction of NADP to NADPH. The knock-down of gapN by antisense peptide nucleic acids (asPNA) significantly reduces viable bacterial counts of S. pyogenes laboratory and macrolide-resistant clinical strains in vitro. As S. pyogenes lacks the oxidative part of the pentose phosphate pathway, GapN appears to be the major NADPH source for the bacterium. Accordingly, other streptococci that carry a complete pentose phosphate pathway are not prone to asPNA-based gapN knock-down. Determination of the crystal structure of the S. pyogenes GapN apo-enzyme revealed an unusual cis-peptide in proximity to the catalytic binding site. Furthermore, using a structural modeling approach, we correctly predicted competitive inhibition of S. pyogenes GapN by erythrose 4-phosphate, indicating that our structural model can be used for in silico screening of specific GapN inhibitors. In conclusion, the data provided here reveal that GapN is a potential target for antimicrobial substances that selectively kill S. pyogenes and other streptococci that lack the oxidative part of the pentose phosphate pathway. |
DOI: | doi:10.3389/fmicb.2022.802427 |
URL: | Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.
Volltext: https://www.frontiersin.org/article/10.3389/fmicb.2022.802427 |
| DOI: https://doi.org/10.3389/fmicb.2022.802427 |
Datenträger: | Online-Ressource |
Sprache: | eng |
K10plus-PPN: | 1797607987 |
Verknüpfungen: | → Zeitschrift |
¬The¬ non-phosphorylating glyceraldehyde-3-phosphate dehydrogenase GapN is a potential new drug target in Streptococcus pyogenes / Eisenberg, Philip [VerfasserIn]; 15 February 2022 (Online-Ressource)