The sequences of seven class D β-lactamases isolated from carbapenem-resistant Acinetobacter baumannii from four continents

ABSTRACTCarbapenem resistance associated with class D β-lactamases is an increasing problem in Acinetobacter baumannii. Most enzymes of this class reported so far belong to two subgroups, 1 and 2; however, a novel class D carbapenemase (OXA-51) has been reported recently which shares 56% and <63% amino-acid identity with subgroups 1 and 2, respectively, and which belongs to a third subgroup. This study describes a further seven novel subgroup 3 β-lactamases in carbapenem-resistant A. baumannii isolates from four continents

Catalysis by hen egg-white lysozyme proceeds via a covalent intermediate

Hen egg-white lysozyme (HEWL) was the first enzyme to have its three-dimensional structure determined by X-ray diffraction techniques(1). A catalytic mechanism, featuring a long-lived oxo-carbenium-ion intermediate, was proposed on the basis of model-building studies(2). The `Phillips' mechanism is widely held as the paradigm for the catalytic mechanism of beta -glycosidases that cleave glycosidic linkages with net retention of configuration of the anomeric centre. Studies with other retaining beta -glycosidases, however, provide strong evidence pointing to a common mechanism for these enzymes that involves a covalent glycosyl-enzyme intermediate, as previously postulated(3). Here we show, in three different cases using electrospray ionization mass spectrometry, a catalytically competent covalent glycosyl-enzyme intermediate during the catalytic cycle of HEWL. We also show the three-dimensional structure of this intermediate as determined by Xray diffraction. We formulate a general catalytic mechanism for all retaining beta -glycosidases that includes substrate distortion, formation of a covalent intermediate, and the electrophilic migration of C1 along the reaction coordinate

High frequency of carbapenem-resistant Acinetobacter baumannii in patients with diabetes mellitus in Saudi Arabia

Carbapenem-resistant Acinetobacter baumannii is becoming increasingly prevalent in patients with diabetes mellitus in the Middle East. We examined the relationship of these bacteria and their resistance mechanisms to the diabetic disease status of patients in Saudi Arabia. Susceptibilities of 271 isolates to carbapenems, tigecycline and colistin were determined, followed by detection of carbapenemase genes. A blaVIM gene was detected in ~95 % of isolates; blaOXA-23 and blaOXA-40 genes were also prevalent. Diabetic patients were significantly more likely to carry carbapenem-resistant isolates. Carbapenem-resistant A. baumannii is a serious problem in diabetic patients, and molecular detection of resistance mechanisms in these isolates is required

Draft Genome Sequence of a Multidrug-Resistant Acinetobacter baumannii Strain from Chile

Date of Acceptance: 20/05/2015 Copyright © 2015 Opazo et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 3.0 Unported license. ACKNOWLEDGMENTS This work was supported through funds granted by the Chilean National Commission for Scientific and Technological Research (CONICYT) and by the National Fund for Scientific and Technological Development (FONDECYT) of Chile (project 3150286).Peer reviewedPublisher PD

Toward New Therapeutics for Skin and Soft Tissue Infections: Propargyl-Linked Antifolates Are Potent Inhibitors of MRSA and Streptococcus pyogenes

Hospital- and community-acquired, complicated skin and soft tissue infections, often attributed to Staphylococcus aureus and Streptococcus pyogenes, present a significant health burden that is associated with increased health care costs and mortality. As these two species are difficult to discern on diagnosis and are associated with differential profiles of drug resistance, the development of an efficacious antibacterial agent that targets both organisms is a high priority. Herein we describe a structure-based drug development effort that has produced highly potent inhibitors of dihydrofolate reductase from both species. Optimized propargyl-linked antifolates containing a key pyridyl substituent display antibacterial activity against both methicillin-resistant S. aureus and S. pyogenes at MIC values below 0.1 µg/mL and minimal cytotoxicity against mammalian cells. Further evaluation against a panel of clinical isolates shows good efficacy against a range of important phenotypes such as hospital- and community-acquired strains as well as strains resistant to vancomycin