β-lactamases, the enzymes responsible for resistance to β-lactam antibiotics, are
widespread among prokaryotic genera. However, current β-lactamase classification
schemes do not represent their present diversity. Here, we propose a workflow to
identify and classify β-lactamases. Initially, a set of curated sequences was
used as a model for the construction of profiles Hidden Markov Models (HMM),
specific for each β-lactamase class. An extensive, nonredundant set of
β-lactamase sequences was constructed from 7 different resistance proteins
databases to test the methodology. The profiles HMM were improved for their
specificity and sensitivity and then applied to fully assembled genomes. Five
hierarchical classification levels are described, and a new class of
β-lactamases with fused domains is proposed. Our profiles HMM provide a better
annotation of β-lactamases, with classes and subclasses defined by objective
criteria such as sequence similarity. This classification offers a solid base to
the elaboration of studies on the diversity, dispersion, prevalence, and
evolution of the different classes and subclasses of this critical enzymatic
activity.