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It functions as a pro-drug that, upon azoreduction by selected gastrointestinal bacteria (including the bacterial triggers of some inflammatory diseases), releases an antioxidant protective molecule, 5-aminosalicylate (5-AS), and the antibacterial molecule sulfapyridine (SP). SSZ, 5-AS and SP were evaluated for growth inhibitory activity against some bacterial triggers of rheumatoid arthritis (\n                    <jats:italic>Proteus<\/jats:italic>\n                    spp.), ankylosing spondylitis (\n                    <jats:italic>Klebsiella pnumoniae<\/jats:italic>\n                    ), multiple sclerosis (\n                    <jats:italic>Acinetobacter baylyi<\/jats:italic>\n                    and\n                    <jats:italic>Pseudomonas aeruginosa<\/jats:italic>\n                    ) and rheumatic fever (\n                    <jats:italic>Streptococcus pyogenes<\/jats:italic>\n                    ). These bacteria have previously been reported to have azoreductase activity and therefore they may locally convert the SSZ pro-drug into 5-AS and SP. The potency of all compounds, as well as a combination of 5-AS and SP, were evaluated under aerobic conditions by MIC, \u01a9FIC and isobologram analysis. Noteworthy antibacterial activity was calculated for SSZ, with MIC values as low as 625\u00a0\u00b5g\/mL against\n                    <jats:italic>P. mirabilis<\/jats:italic>\n                    and\n                    <jats:italic>K. pneumoniae<\/jats:italic>\n                    . The azoreduction product SP had substantially more potent antibacterial activity (MICs 78\u2013625\u00a0\u00b5g\/mL). It was particularly potent against the\n                    <jats:italic>Proteus<\/jats:italic>\n                    spp. triggers of rheumatoid arthritis. Whilst 5-AS also inhibited bacterial growth, it was substantially less potent than SP. However, 5-AS potentiated the activity of SP when tested in combination. Indeed, synergy was noted for the combination against\n                    <jats:italic>P. vulgaris<\/jats:italic>\n                    , whilst additive effects were recorded against\n                    <jats:italic>P. mirabilis<\/jats:italic>\n                    and\n                    <jats:italic>K. pneumoniae<\/jats:italic>\n                    . Taken together, these results highlight the pro-drug properties of SZ against the bacterial triggers of selected inflammatory diseases. Future studies into the pharmacological properties of SSZ, as well as the 5-AS and SP combination are warranted. In particular, these compounds should be evaluated against additional strains of these bacteria (including antibiotic-resistant strains), as well as against bacterial triggers of further inflammatory diseases.\n                  <\/jats:p>","DOI":"10.1007\/s10787-026-02141-5","type":"journal-article","created":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T06:10:40Z","timestamp":1771222240000},"page":"1811-1821","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Re-evaluating the antibacterial properties of DMARD and pro-drug sulphasalazine against autoimmune bacterial triggers after eighty years"],"prefix":"10.1007","volume":"34","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8732-8513","authenticated-orcid":false,"given":"Ian Edwin","family":"Cock","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael Wellesley","family":"Whitehouse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,16]]},"reference":[{"key":"2141_CR1","doi-asserted-by":"publisher","first-page":"118083","DOI":"10.1016\/j.molliq.2021.118083","volume":"348","author":"MJ Ansari","year":"2022","unstructured":"Ansari MJ, Soltani A, Ramezanitaghartapeh M, Singla P, Aghaei M, Fadafan HK, Khales SA, Shariati M, Shirzad-Aski H, Balakheyli H, Imam SS (2022) Improved antibacterial activity of sulfasalazine loaded fullerene derivative: computational and experimental studies. 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