{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T11:53:24Z","timestamp":1788954804250,"version":"build-2803163510"},"reference-count":56,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,2,15]],"date-time":"2022-02-15T00:00:00Z","timestamp":1644883200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:p>\n                    The strict human pathogen\n                    <jats:italic>Streptococcus pyogenes<\/jats:italic>\n                    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\n                    <jats:italic>S. pyogenes<\/jats:italic>\n                    . GapN converts glyceraldehyde 3-phosphate into 3-phosphoglycerate coupled to the reduction of NADP to NADPH. The knock-down of\n                    <jats:italic>gapN<\/jats:italic>\n                    by antisense peptide nucleic acids (asPNA) significantly reduces viable bacterial counts of\n                    <jats:italic>S. pyogenes<\/jats:italic>\n                    laboratory and macrolide-resistant clinical strains\n                    <jats:italic>in vitro<\/jats:italic>\n                    . As\n                    <jats:italic>S. pyogenes<\/jats:italic>\n                    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\n                    <jats:italic>gapN<\/jats:italic>\n                    knock-down. Determination of the crystal structure of the\n                    <jats:italic>S. pyogenes<\/jats:italic>\n                    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\n                    <jats:italic>S. pyogenes<\/jats:italic>\n                    GapN by erythrose 4-phosphate, indicating that our structural model can be used for\n                    <jats:italic>in silico<\/jats:italic>\n                    screening of specific GapN inhibitors. In conclusion, the data provided here reveal that GapN is a potential target for antimicrobial substances that selectively kill\n                    <jats:italic>S. pyogenes<\/jats:italic>\n                    and other streptococci that lack the oxidative part of the pentose phosphate pathway.\n                  <\/jats:p>","DOI":"10.3389\/fmicb.2022.802427","type":"journal-article","created":{"date-parts":[[2022,2,15]],"date-time":"2022-02-15T01:50:27Z","timestamp":1644889827000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["The Non-phosphorylating Glyceraldehyde-3-Phosphate Dehydrogenase GapN Is a Potential New Drug Target in Streptococcus pyogenes"],"prefix":"10.3389","volume":"13","author":[{"given":"Philip","family":"Eisenberg","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leon","family":"Albert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Teuffel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Zitzow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Michaelis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane","family":"Jarick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clemens","family":"Sehlke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Gro\u00dfe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Bader","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ariane","family":"Nunes-Alves","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernd","family":"Kreikemeyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hermann","family":"Schindelin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca C.","family":"Wade","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomas","family":"Fiedler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,2,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/srep20832","article-title":"Impact of different cell penetrating peptides on the efficacy of antisense therapeutics for targeting intracellular pathogens.","volume":"6","author":"Abushahba","year":"2016","journal-title":"Sci. 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