A Genotype-Phenotype Correlation Study of SHV β-Lactamases Offers New Insight into SHV Resistance Profiles
Svetlana Neubauer, Sara Madzgalla, Mike Marquet, Anne Klabunde, Bernd Büttner, Alexander Göhring, Christian Brandt, K.‐H. Feller, Mathias W. Pletz, Oliwia Makarewicz
Abstract
The SHV β-lactamases (BLs) have undergone strong allele diversification that has changed their substrate specificities. Based on 147 NCBI entries for SHV alleles, in silico mathematical models predicted 5 positions as relevant for the β-lactamase inhibitor (BLI)-resistant (2br) phenotype, 12 positions as relevant for the extended-spectrum BL (ESBL) (2be) phenotype, and 2 positions as related solely to the narrow-spectrum (2b) phenotype. These positions and six additional positions described in other studies (including one promoter mutation) were systematically substituted and investigated for their substrate specificities in a BL-free Escherichia coli background, representing, to our knowledge, the most comprehensive substrate and substitution analysis for SHV alleles to date.