β-Lactamases enable resistance to almost all β-lactam antibiotics. Pioneering work revealed that acyclic boronic acids can act as 'transition state analogue' inhibitors of nucleophilic serine enzymes, including serine-β-lactamases. Here we report biochemical and biophysical analyses revealing that cyclic boronates potently inhibit both nucleophilic serine and zinc-dependent β-lactamases by a me...

The veterinary cephalosporin drug ceftiofur is rapidly degraded in the bovine intestinal tract. A cylinder-plate assay was used to detect microbiologically active ceftiofur, and high-performance liquid chromatography-mass spectrometry analysis was used to quantify the amount of ceftiofur remaining after incubation with bovine intestinal anaerobic bacteria, which were isolated from colon content...

The occurrence of multidrug-resistant Serratia marcescens strains producing metallo-β-lactamases or extended-spectrum β-lactamases represents a serious public health threat. Here, we report the draft genome sequence of a multidrug-resistant carbapenemase-producing Serratia marcescens isolate recovered from the bronchoalveolar lavage specimen of a patient suffering from chronic obstructive pulmo...

Metallo-β-lactamases can hydrolyze a broad range of β-lactam antibiotics and no effective inhibitors could be used in the clinic. Therefore, the discovery of metallo-β-lactamase inhibitors has attracted much attention in recent years. In this study, a support vector machine (SVM) that separates compounds into positives and negatives, combined with docking method was employed for virtual screeni...

Acquired resistance is through the production of AmpC Beta Lactamases (AmpC), Extended Spectrum Beta Lactamases (ESBL) and Metallo Beta-Lactamases Enzymes (MBL). Resistance to β-lactam antibiotics is associated with production of ESBL which can hydrolyze oxyimino β-lactams such as cefotaxime, ceftriaxone, ceftazidime and monobactams, however, without any effect on cephamycins, carbapenems and r...

Metallo-β-lactamase-producing Pseudomonas aeruginosa (MPPA) is an important nosocomial pathogen that shows resistance to all β-lactam antibiotics except monobactams. There are various types of metallo-β-lactamases (MBLs) in carbapenem-resistant P. aeruginosa including Imipenemase (IMP), Verona integron-encoded metallo-β-lactamase (VIM), Sao Paulo metallo-β-lactamase (SPM), Germany imipenemase (...

OP0595 is a novel diazabicyclooctane which, like avibactam, inhibits class A and C β-lactamases. In addition, unlike avibactam, it has antibacterial activity, with MICs of 0.5 to 4 μg/ml for most members of the family Enterobacteriaceae, owing to inhibition of PBP2; moreover, it acts synergistically with PBP3-active β-lactams independently of β-lactamase inhibition, via an "enhancer effect." En...

A population analysis of 103 multidrug-resistant Pseudomonas aeruginosa isolates from Croatian hospitals was performed. Twelve sequence types (STs) were identified, with a predominance of international clones ST235 (serotype O11 [41%]), ST111 (serotype O12 [15%]), and ST132 (serotype O6 [11%]). Overexpression of the natural AmpC cephalosporinase was common (42%), but only a few ST235 or ST111 i...

Carbapenem resistance caused by metallo-β-lactamases is a serious global challenge that, if not tackled efficiently, expected to lead millions of deaths in the coming decades. Verona-integron encoded metallo-β-lactamase 2 (VIM-2) bacterial enzyme that has been reported from multidrug-resistant nosocomial isolates Pseudomonas aeruginosa and other Gram-negative pathogens. As it hydrolyzes most β-...

Klebsiella pneumoniae strains co-producing klebsiella pneumoniae carbapenemase (KPC) and verona integron-encoded metallo-beta-lactamase (VIM) are frequently isolated in Greece and have also occurred in other European countries. Conventional combined disc tests exhibit low sensitivity against these emerging pathogens. We have evaluated modifications of the KPC/Metallo-β-Lactamase Confirmation ki...