Correlation Between the Spread of IMP-producing Bacteria and the Promoter Strength of Bla Genes

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