The oxacillinase variant, OXA-1152, in Pandoraea sputorum contributes to discrepancies in carbapenem resistance
- iScience. 2025 Mar 28;28(5):112311. doi: 10.1016/j.isci.2025.112311.
- 1. Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan, China.
- 2. Institute of Health Inspection and Testing, Hubei Provincial Center for Disease Control and Prevention, Wuhan, China.
- 3. Department of Spine Surgery and Musculoskeletal Tumor, Zhongnan Hospital of Wuhan University, Wuhan, China.
- 4. National 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, China.
- 5. Hubei Provincial Clinical Research Center for Molecular Diagnostics, Wuhan, China.
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, bla OXA-1152, in 12 Pandoraea sputorum strains from Wuhan, China. Deleting bla OXA-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.