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

The first report of transmissible carbapenem resistance encoded by bla_IMP-1 was discovered in Pseudomonas aeruginosa GN17203 in 1988, and bla_IMP-1 has since been detected in other bacteria, including Enterobacterales. Currently, many variants of bla_IMPs exist, and point mutations in the bla_IMP promoter have been shown to alter promoter strength. For example, the promoter (Pc) of bla_IMP-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 bla_IMPs from 14,529 genome data of Pseudomonadota and performed multiple alignment analyses. The results of promoter analysis of the 115 retrieved bla_IMPs 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 bla_IMP 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 bla_IMPs 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 bla_IMP genes, including promoter analysis, is necessary for global surveillance of carbapenem-resistant bacteria.