Outbreaks of multidrug-resistant @entity2348 have become more frequent worldwide owing to the emergence of several different classes of b-lactamases. In this study, the molecular, biochemical and structural characteristics of an @entity3064 -derived cephalosporinase (ADC)-type class C b-lactamase, ADC-68, isolated from the @entity2893 -resistant A. baumannii D015 were investigated. The blaADC-68 gene which encodes ADC-68 was confirmed to exist on the chromosome via Southern blot analysis and draft genome sequencing. The catalytic kinetics of b-lactams and their MICs (minimum inhibitory concentrations) for A. baumannii D015 and purified ADC-68 (a carbapenemase obtained from this strain) were assessed: the strain was resistant to penicillins, narrow-spectrum and extended-spectrum cephalosporins, and @entity2888 , which were hydrolyzed by ADC-68. The crystal structure of ADC-68 was determined at a resolution of 1.8     . The structure of ADC-68 was compared with that of ADC-1 (a non-carbapenemase); differences were found in the central part of the   -loop and the C-loop constituting the edge of the R1 and R2 subsites and are close to the catalytic @entity563 residue Ser66. The ADC-68 C-loop was stabilized in the open conformation of the upper R2 subsite and could better accommodate carbapenems with larger R2 side chains. Furthermore, a wide-open conformation of the R2-loop allowed ADC-68 to bind to and hydrolyze extended-spectrum cephalosporins. Therefore, ADC-68 had enhanced catalytic efficiency against these clinically important b-lactams (extended-spectrum cephalosporins and carbapenems). ADC-68 is the first reported enzyme among the chromosomal class C b-lactamases to possess class C extended-spectrum b-lactamase and carbapenemase activities.

Structure of ADC-68, a novel XXXX -hydrolyzing class C extended-spectrum b-lactamase isolated from @entity3064 .

@entity2348 :: ('MESH:D001424', 'Disease') :: ['bacterial infections'] @entity2893 :: ('CHEBI:46765', 'Chemical') :: ['carbapenem'] @entity2888 :: ('MESH:D015780', 'Chemical') :: ['carbapenems'] @entity563 :: ('CHEBI:17822', 'Chemical') :: ['serine'] @entity3064 :: ('470', 'Species') :: ['Acinetobacter']
@entity2893 :: (CHEBI:46765,Chemical) :: ['carbapenem']
