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The bacterial folate biosynthesis enzyme dihydropteroate synthase (DHPS), which adds\n                    <jats:italic>p<\/jats:italic>\n                    \u2010aminobenzoate (pABA) to an activated pterin precursor, is an important antibiotic target. Both the broad\u2010spectrum\n                    <jats:italic>p<\/jats:italic>\n                    \u2010aminobenzenesulfonamide antibiotics, and the drug\n                    <jats:italic>p<\/jats:italic>\n                    \u2010aminosalicylate (PAS, 2\u2010hydroxy\u2010pABA) with high selectivity for\n                    <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                    , are competitive DHPS substrates. The adducts formed from these drugs, DHP\u2010sulfonamides (sulfapterins) and 2\u2032\u2010hydroxyfolate metabolites, respectively, have been reported to exhibit antifolate activity in studies of microorganisms. The presence of these DHP\u2010adducts and their effects on the host organism are largely undetermined; however, their close structural relationship to dihydrofolate (DHF) suggests that they are likely to mediate some side effects reported for these antibiotics. Naturally occurring pABA analogs that probably function similar to DHPS\u2010targeted antibiotics have been identified in carrots and bacteria.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:boxed-text content-type=\"box\" position=\"anchor\">\n                      <jats:caption>\n                        <jats:title>Impact statement<\/jats:title>\n                      <\/jats:caption>\n                      <jats:p>pABA analogs represent an important class of antibiotics, that are converted into dihydrofolate analogs by organisms present in the human microbiome. These analogs may mediate reported side\u2010effects associated with these antibiotics. Several naturally occurring pABA mimics have been identified that are likely to exhibit antibiotic activity.<\/jats:p>\n                    <\/jats:boxed-text>\n                  <\/jats:p>","DOI":"10.1002\/1873-3468.70252","type":"journal-article","created":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T08:25:05Z","timestamp":1768292705000},"page":"1288-1317","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Microbiome\u2010generated antifolates"],"prefix":"10.1002","volume":"600","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9108-8463","authenticated-orcid":false,"given":"Robert E.","family":"London","sequence":"first","affiliation":[{"name":"Genome Integrity and Structural Biology Laboratory National Institute of Environmental Health Sciences, NIH  Research Triangle Park NC 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