The oxacillinase variant, OXA-1152, in Pandoraea sputorum contributes to discrepancies in carbapenem resistance
Summary: Pandoraea species are emerging multidrug-resistant pathogens with inconsistent carbapenem susceptibility, being resistant to meropenem but susceptible to imipenem, which complicates treatment. Here, we identified a previously uncharacterized oxacillinase gene, blaOXA-1152, in 12 Pandoraea s...
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Elsevier
2025-05-01
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004225005723 |
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| author | Yating Zhang Shuo Dai Xiaobin Zhu Ying Dai Guoming Li Xiaoli Du Yirong Li Xiao Xiao |
| author_facet | Yating Zhang Shuo Dai Xiaobin Zhu Ying Dai Guoming Li Xiaoli Du Yirong Li Xiao Xiao |
| author_sort | Yating Zhang |
| collection | DOAJ |
| description | Summary: Pandoraea species are emerging multidrug-resistant pathogens with inconsistent carbapenem susceptibility, being resistant to meropenem but susceptible to imipenem, which complicates treatment. Here, we identified a previously uncharacterized oxacillinase gene, blaOXA-1152, in 12 Pandoraea sputorum strains from Wuhan, China. Deleting blaOXA-1152 reduced meropenem and imipenem minimal inhibitory concentrations (MICs) by 64- and 4-fold, respectively, while reintroducing it into P. sputorum and E. coli DH5α restored resistance. Mechanistically, OXA-1152 exhibited stronger binding and hydrolysis efficiency for meropenem than imipenem. Combining avibactam with carbapenems restored susceptibility to meropenem and further reduced imipenem MICs, highlighting OXA-1152’s role in resistance variation. These findings reveal the molecular basis of carbapenem resistance discrepancy in Pandoraea and suggest avibactam-carbapenem combinations as a promising therapeutic strategy, offering broader implications for treating multidrug-resistant infections. |
| format | Article |
| id | doaj-art-aa676da2b8cd4be4b9d50d79f2bc6391 |
| institution | DOAJ |
| issn | 2589-0042 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj-art-aa676da2b8cd4be4b9d50d79f2bc63912025-08-20T02:55:32ZengElsevieriScience2589-00422025-05-0128511231110.1016/j.isci.2025.112311The oxacillinase variant, OXA-1152, in Pandoraea sputorum contributes to discrepancies in carbapenem resistanceYating Zhang0Shuo Dai1Xiaobin Zhu2Ying Dai3Guoming Li4Xiaoli Du5Yirong Li6Xiao Xiao7Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan, China; Institute of Health Inspection and Testing, Hubei Provincial Center for Disease Control and Prevention, Wuhan, ChinaDepartment of Spine Surgery and Musculoskeletal Tumor, Zhongnan Hospital of Wuhan University, Wuhan, ChinaDepartment of Spine Surgery and Musculoskeletal Tumor, Zhongnan Hospital of Wuhan University, Wuhan, ChinaInstitute of Health Inspection and Testing, Hubei Provincial Center for Disease Control and Prevention, Wuhan, ChinaInstitute of Health Inspection and Testing, Hubei Provincial Center for Disease Control and Prevention, Wuhan, ChinaNational Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases and National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, ChinaDepartment of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan, China; Hubei Provincial Clinical Research Center for Molecular Diagnostics, Wuhan, ChinaDepartment of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan, China; Hubei Provincial Clinical Research Center for Molecular Diagnostics, Wuhan, China; Corresponding authorSummary: Pandoraea species are emerging multidrug-resistant pathogens with inconsistent carbapenem susceptibility, being resistant to meropenem but susceptible to imipenem, which complicates treatment. Here, we identified a previously uncharacterized oxacillinase gene, blaOXA-1152, in 12 Pandoraea sputorum strains from Wuhan, China. Deleting blaOXA-1152 reduced meropenem and imipenem minimal inhibitory concentrations (MICs) by 64- and 4-fold, respectively, while reintroducing it into P. sputorum and E. coli DH5α restored resistance. Mechanistically, OXA-1152 exhibited stronger binding and hydrolysis efficiency for meropenem than imipenem. Combining avibactam with carbapenems restored susceptibility to meropenem and further reduced imipenem MICs, highlighting OXA-1152’s role in resistance variation. These findings reveal the molecular basis of carbapenem resistance discrepancy in Pandoraea and suggest avibactam-carbapenem combinations as a promising therapeutic strategy, offering broader implications for treating multidrug-resistant infections.http://www.sciencedirect.com/science/article/pii/S2589004225005723health sciencesmedicinenatural sciencesbiological sciencesmicrobiologymedical microbiology |
| spellingShingle | Yating Zhang Shuo Dai Xiaobin Zhu Ying Dai Guoming Li Xiaoli Du Yirong Li Xiao Xiao The oxacillinase variant, OXA-1152, in Pandoraea sputorum contributes to discrepancies in carbapenem resistance iScience health sciences medicine natural sciences biological sciences microbiology medical microbiology |
| title | The oxacillinase variant, OXA-1152, in Pandoraea sputorum contributes to discrepancies in carbapenem resistance |
| title_full | The oxacillinase variant, OXA-1152, in Pandoraea sputorum contributes to discrepancies in carbapenem resistance |
| title_fullStr | The oxacillinase variant, OXA-1152, in Pandoraea sputorum contributes to discrepancies in carbapenem resistance |
| title_full_unstemmed | The oxacillinase variant, OXA-1152, in Pandoraea sputorum contributes to discrepancies in carbapenem resistance |
| title_short | The oxacillinase variant, OXA-1152, in Pandoraea sputorum contributes to discrepancies in carbapenem resistance |
| title_sort | oxacillinase variant oxa 1152 in pandoraea sputorum contributes to discrepancies in carbapenem resistance |
| topic | health sciences medicine natural sciences biological sciences microbiology medical microbiology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004225005723 |
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