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Correlation between the spread of IMP-producing bacteria and the promoter strength of blaIMP genes

The Journal of Antibiotics volume 77, pages 315–323 (2024)Cite this article

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Abstract

The first report of transmissible carbapenem resistance encoded by blaIMP-1 was discovered in Pseudomonas aeruginosa GN17203 in 1988, and blaIMP-1 has since been detected in other bacteria, including Enterobacterales. Currently, many variants of blaIMPs exist, and point mutations in the blaIMP promoter have been shown to alter promoter strength. For example, the promoter (Pc) of blaIMP-1, first reported in P. aeruginosa GN17203, was a weak promoter (PcW) with low-level expression intensity. This study investigates whether point mutations in the promoter region have helped to create strong promoters under antimicrobial selection pressure. Using bioinformatic approaches, we retrieved 115 blaIMPs from 14,529 genome data of Pseudomonadota and performed multiple alignment analyses. The results of promoter analysis of the 115 retrieved blaIMPs showed that most of them used the Pc located in class 1 integrons (n = 112, 97.4%). The promoter analysis by year revealed that the blaIMP population with the strong promoter, PcS, was transient. In contrast, the PcW-TG population, which had acquired a TGn-extended −10 motif in PcW and had an intermediate promoter strength, gradually spread throughout the world. An inverse correlation between Pc promoter strength and Intl1 integrase excision efficiency has been reported previously [1]. Because of this trade-off, it is unlikely that blaIMPs with strong promoters will increase rapidly, but the possibility that promoter strength will increase with the use of other integrons cannot be ruled out. Monitoring of the blaIMP genes, including promoter analysis, is necessary for global surveillance of carbapenem-resistant bacteria.

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Acknowledgements

This work was supported in part by grants from the Ministry of Education, Culture, Sports, Science and Technology, KAKENHI grants from the Japan Society for the Promotion of Science (nos. 19K07542 to A.A. and 20K07485, 23K06531 to A.K.) and AMED grants (nos. JP20nk0101552 to A.A. and JP22nk0101587 to A.A.). The funders had no role in the study design, data collection or analysis, the decision to publish, or the preparation of the manuscript.

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Authors and Affiliations

  1. Graduate School of Infection Control Sciences, Kitasato University, 5-9-1 Shirokane, Minato-Ku, Tokyo, 108-8641, Japan

    Yuta Kikuchi, Asaomi Kuwae, Yukihiro Asami, Yuki Inahashi & Akio Abe

  2. Ōmura Satoshi Memorial Institute, Kitasato University, 5-9-1 Shirokane, Minato-Ku, Tokyo, 108-8641, Japan

    Mariko Yoshida, Asaomi Kuwae, Yukihiro Asami, Yuki Inahashi & Akio Abe

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  1. Yuta Kikuchi
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Correspondence to Akio Abe.

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Kikuchi, Y., Yoshida, M., Kuwae, A. et al. Correlation between the spread of IMP-producing bacteria and the promoter strength of blaIMP genes. J Antibiot 77, 315–323 (2024). https://doi.org/10.1038/s41429-024-00715-5

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