2. Academic Validation
  3. The oxacillinase variant, OXA-1152, in Pandoraea sputorum contributes to discrepancies in carbapenem resistance

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.
Yating Zhang 1 2,  Shuo Dai 3,  Xiaobin Zhu 3,  Ying Dai 2,  Guoming Li 2,  Xiaoli Du 4,  Yirong Li 1 5,  Xiao Xiao 1 5
Affiliations

Affiliations

  • 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.
PMID: 40454099 DOI: 10.1016/j.isci.2025.112311
Abstract

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.

Keywords

biological sciences; health sciences; medical microbiology; medicine; microbiology; natural sciences.

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