Differences in β-lactamase activity and carbapenem resistance among the <i>Bacillus cereus</i> group

The <i>Bacillus cereus</i> group causes severe nosocomial infections. This group carries the chromosomal β-lactamases, including <i>bla1</i> and <i>BcII</i>, which contribute to β-lactam resistance; however, the β-lactam resistance mechanisms are poorly understood. We performed genomic and phenotypic analyses of 48 clinical isolates from blood cultures and the reference strain ATCC14579 to clarify these mechanisms. Genomic analyses included species identification, multilocus sequence typing (MLST), and detection of β-lactamase genes using whole-genome sequencing. β-Lactam susceptibility testing, enzyme activity assays, and RT-qPCR of β-lactamases were performed. For this analysis, we developed a method to measure the enzyme activity of <i>B. cereus</i> group. The 48 isolates comprised three species (30 <i>Bacillus mosaicus</i>, 9 <i>Bacillus cereus sensu stricto</i> (<i>s.s</i>.), and 9 <i>Bacillus luti</i>) and 28 sequence types. Although all <i>B. luti</i> isolates lacked carbapenemase genes, they exhibited higher minimum inhibitory concentration (MIC) ranges for ampicillin and meropenem. The enzyme activity patterns were categorized as constitutive, inducible, or silent. All <i>B. luti</i> isolates and some <i>B. mosaicus</i> and <i>B. cereus s.s</i>. isolates displayed constitutive enzyme activity for penicillin G, whereas most <i>B. mosaicus</i> and <i>B. cereus s.s</i>. isolates displayed inducible activity, and five displayed silent activity. In the inducible group, the induced activity appeared to be accompanied by elevated penicillinase and carbapenemase expression. This is the first study to demonstrate interspecies variability within the <i>B. cereus</i> group regarding the presence of carbapenemase genes and β-lactam resistance profiles. These findings provide crucial insights into β-lactam resistance mechanisms in this bacterial group and provide a foundation for further research.