Functional and Structural Characterization of OXA-935, a Novel OXA-10-Family β-Lactamase from Pseudomonas aeruginosa
Nathan B. Pincus, Mónica Rosas‐Lemus, Samuel W. M. Gatesy, Hanna K. Bertucci, J.S. Brunzelle, G. Minasov, L. Shuvalova, Marine Lebrun-Corbin, K.J.F. Satchell, Egon A. Ozer, Alan R. Hauser, Kelly E. R. Bachta
Abstract
revealed that OXA-935 conferred ceftazidime resistance. To better understand the impacts of the variant amino acids, we determined the crystal structures of OXA-14 and OXA-935. Compared to OXA-14, the F153S mutation in OXA-935 conferred increased flexibility in the omega (Ω) loop. Amino acid changes that confer extended spectrum cephalosporinase activity to OXA-10-family β-lactamases are concerning, given the rising reliance on novel β-lactam/β-lactamase inhibitor combinations, such as ceftolozane-tazobactam and ceftazidime-avibactam, to treat MDR P. aeruginosa infections.