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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Main Authors: Yating Zhang, Shuo Dai, Xiaobin Zhu, Ying Dai, Guoming Li, Xiaoli Du, Yirong Li, Xiao Xiao
Format: Article
Language:English
Published: Elsevier 2025-05-01
Series:iScience
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Online Access:http://www.sciencedirect.com/science/article/pii/S2589004225005723
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Summary: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.
ISSN:2589-0042