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Due to its recognized potential as a bioterrorism agent, it is critical that appropriate antimicrobial agents are available for post-exposure prophylaxis and treatment of melioidosis. Cefepime\u2013taniborbactam is a novel \u03b2-lactam\u2013\u03b2-lactamase inhibitor combination in clinical development, with promising activity against Gram-negative bacteria producing class A, B, C, and\/or D \u03b2-lactamases. Herein, we demonstrate the inhibitory activity of taniborbactam against PenI, the class A \u03b2-lactamase produced by\n                      <jats:italic toggle=\"yes\">B. pseudomallei<\/jats:italic>\n                      . Isogenic\n                      <jats:italic toggle=\"yes\">Escherichia coli<\/jats:italic>\n                      strains producing PenI and its ceftazidime-resistance\u2013conferring variants (C69Y and P167S) showed ceftazidime minimum inhibitory concentration (MIC) of 64 mg\/L for the strain producing PenI and 1,024 mg\/L for the strains producing the variants, whereas cefepime MIC was 128\u2013256 mg\/L for these three strains. While the addition of avibactam decreased ceftazidime MIC to 1 mg\/L for PenI and 8\u201316 mg\/L for the variants, the addition of taniborbactam decreased cefepime MIC to \u22640.5 mg\/L for PenI and the variants. Similarly, an 8-fold reduction of the cefepime MIC upon addition of taniborbactam was observed in an avirulent\n                      <jats:italic toggle=\"yes\">B. pseudomallei<\/jats:italic>\n                      strain. Furthermore, taniborbactam inhibited PenI and its C69Y variant with an apparent\n                      <jats:italic toggle=\"yes\">K<\/jats:italic>\n                      <jats:sub>i<\/jats:sub>\n                      of 0.11 and 3.1 \u00b5M, respectively. Lastly, co-crystallography and molecular dynamics simulations showed that taniborbactam induced the formation of a disulfide bond between Cys77 and Cys123, which destabilizes the deacylation water and strengthens the taniborbactam\u2013PenI complex. These results support the development of cefepime\u2013taniborbactam as a promising agent for the treatment of infections by\n                      <jats:italic toggle=\"yes\">B. pseudomallei<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/aac.00787-25","type":"journal-article","created":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T14:53:54Z","timestamp":1757688834000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":2,"title":["<i>Burkholderia pseudomallei<\/i>\n                    PenI \u03b2-lactamase and variants are potently inhibited by taniborbactam"],"prefix":"10.1128","volume":"69","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1380-9824","authenticated-orcid":true,"given":"Maria 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Prevalence of blaPenA and blaOXA in Burkholderia pseudomallei isolated from patients at sappasitthiprasong hospital and their susceptibility to ceftazidime and carbapenems. J Med Assoc Thai 99:S12\u2013S16.","journal-title":"J Med Assoc Thai"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkf165"},{"key":"e_1_3_3_19_2","unstructured":"CDC. 2024. Clinical overview of melioidosis. Available from: https:\/\/www.cdc.gov\/melioidosis\/hcp\/clinical-overview\/index.html. 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