# Differences in β-lactamase activity and carbapenem resistance among the Bacillus cereus group

## TL;DR

This study explores how different species in the Bacillus cereus group show varying levels of resistance to β-lactam antibiotics, including carbapenems, through differences in β-lactamase activity.

## Contribution

The study introduces a method to measure β-lactamase enzyme activity and reveals interspecies variability in resistance mechanisms within the B. cereus group.

## Key findings

- Bacillus luti isolates showed higher resistance to ampicillin and meropenem despite lacking carbapenemase genes.
- β-lactamase activity in the B. cereus group was categorized as constitutive, inducible, or silent.
- Inducible enzyme activity was linked to elevated penicillinase and carbapenemase expression.

## Abstract

The Bacillus cereus group causes severe nosocomial infections. This group carries the chromosomal β-lactamases, including bla1 and BcII, 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 B. cereus group. The 48 isolates comprised three species (30 Bacillus mosaicus, 9 Bacillus cereus sensu stricto (s.s.), and 9 Bacillus luti) and 28 sequence types. Although all B. luti 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 B. luti isolates and some B. mosaicus and B. cereus s.s. isolates displayed constitutive enzyme activity for penicillin G, whereas most B. mosaicus and B. cereus s.s. 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 B. cereus 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.