CBMAR: A comprehensive b-lactamase molecular annotation resource

Abstract

b-Lactam antibiotics are among the most widely used antibiotics against microbial pathogens. However, enzymatic hydrolysis of these antibiotics by bacterial b-lactamases is increasingly compromising their efficiency. Although new generation b-lactam antibiotics have been developed to combat antibiotic resistance, b-lactamases have also evolved along with the new variants of the substrate. A strong selection pressure from the newer generation of b-lactam antibiotics has resulted in evolution of different families within each class of b-lactamase. To facilitate detailed characterization of different families of b-lactamases, we have created a database, CBMAR, which facilitates comprehensive molecular annotation and discovery of novel b-lactamases. As against the limited scope of other existing similar databases, CBMAR provides information useful for molecular and biochemical characterization of each family of b-lactamase. The basic architecture of CBMAR is based on Ambler classification, which divides b-lactamases as serine (Classes A, C and D) and metallo-b-lactamases (Class B). Each class is further divided into several families on the basis of their hydrolytic character. In CBMAR, each family is annotated with (i) sequence variability, (ii) antibiotic resistance profile, (iii) inhibitor susceptibility, (iv) active site, (v) family fingerprints, (vi) mutational profile, (vii) variants, (viii) gene location, (ix) phylogenetic tree and several other features. Each entry also has external links to the relevant protein/nucleotide sequence and structure databases. The database also supports sequence similarity searches using BLAST and assigns a new b-lactamase protein to its respective family on the basis of family-specific fingerprint.