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In yeast, phosphoglucomutase (PGM) plays a crucial role in carbohydrate metabolism by interconverting glucose 1-phosphate and glucose 6-phosphate, a vital step in UDP pools for \u03b2-glucan cell wall formation. This pathway has not yet been defined in\n              <jats:italic>Pneumocystis<\/jats:italic>\n              . Herein, we surveyed the\n              <jats:italic>Pneumocystis jirovecii<\/jats:italic>\n              and\n              <jats:italic>Pneumocystis murina<\/jats:italic>\n              genomes, which predicted a homolog of the\n              <jats:italic>Saccharomyces cerevisiae<\/jats:italic>\n              major PGM enzyme. Furthermore, we show that PjPgm2p and PmPgm2p function similarly to the yeast counterpart. When both\n              <jats:italic>Pneumocystis pgm2<\/jats:italic>\n              homologs are heterologously expressed in\n              <jats:italic>S. cerevisiae pgm2\u0394<\/jats:italic>\n              cells, both genes can restore growth and sedimentation rates to wild-type levels. Additionally, we demonstrate that yeast\n              <jats:italic>pgm2\u0394<\/jats:italic>\n              cell lysates expressing the two\n              <jats:italic>Pneumocystis pgm2<\/jats:italic>\n              transcripts individually can restore PGM activities significantly altered in the yeast\n              <jats:italic>pgm2\u0394<\/jats:italic>\n              strain. The addition of lithium, a competitive inhibitor of yeast PGM activity, significantly reduces PGM activity. Next, we tested the effects of lithium on\n              <jats:italic>P. murina<\/jats:italic>\n              viability\n              <jats:italic>ex vivo<\/jats:italic>\n              and found the compound displays significant anti-\n              <jats:italic>Pneumocystis<\/jats:italic>\n              activity. Finally, we demonstrate that a para-aryl derivative (ISFP10) with known inhibitory activity against the\n              <jats:italic>Aspergillus fumigatus<\/jats:italic>\n              PGM protein and exhibiting 50-fold selectivity over the human PGM enzyme homolog can also significantly reduce Pmpgm2 activity\n              <jats:italic>in vitro<\/jats:italic>\n              . Collectively, our data genetically and functionally validate phosphoglucomutases in both\n              <jats:italic>P. jirovecii<\/jats:italic>\n              and\n              <jats:italic>P. murina<\/jats:italic>\n              and suggest the potential of this protein as a selective therapeutic target for individuals with\n              <jats:italic>Pneumocystis<\/jats:italic>\n              pneumonia.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/aac.00756-23","type":"journal-article","created":{"date-parts":[[2024,1,23]],"date-time":"2024-01-23T14:00:25Z","timestamp":1706018425000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":6,"title":["Characterization of the\n            <i>Pneumocystis jirovecii<\/i>\n            and\n            <i>Pneumocystis murina<\/i>\n            phosphoglucomutases (Pgm2s): a potential target for\n            <i>Pneumocystis<\/i>\n            therapy"],"prefix":"10.1128","volume":"68","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0364-3311","authenticated-orcid":false,"given":"Theodore J.","family":"Kottom","sequence":"first","affiliation":[{"name":"Department of Medicine, Thoracic Diseases Research Unit, Mayo Clinic, Rochester, Minnesota, USA"},{"name":"Department of Biochemistry, Thoracic Diseases Research Unit, Mayo Clinic, Rochester, Minnesota, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva M.","family":"Carmona","sequence":"additional","affiliation":[{"name":"Department of Medicine, Thoracic Diseases Research Unit, Mayo Clinic, Rochester, Minnesota, USA"},{"name":"Department of Biochemistry, Thoracic Diseases Research Unit, Mayo Clinic, Rochester, Minnesota, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5671-6874","authenticated-orcid":true,"given":"Andrew H.","family":"Limper","sequence":"additional","affiliation":[{"name":"Department 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