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      Acquired Antibiotic Resistance Genes: An Overview

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          Abstract

          In this review an overview is given on antibiotic resistance (AR) mechanisms with special attentions to the AR genes described so far preceded by a short introduction on the discovery and mode of action of the different classes of antibiotics. As this review is only dealing with acquired resistance, attention is also paid to mobile genetic elements such as plasmids, transposons, and integrons, which are associated with AR genes, and involved in the dispersal of antimicrobial determinants between different bacteria.

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          Most cited references 149

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          Extended-Spectrum β-Lactamases: a Clinical Update

          Extended-spectrum β-lactamases (ESBLs) are a rapidly evolving group of β-lactamases which share the ability to hydrolyze third-generation cephalosporins and aztreonam yet are inhibited by clavulanic acid. Typically, they derive from genes for TEM-1, TEM-2, or SHV-1 by mutations that alter the amino acid configuration around the active site of these β-lactamases. This extends the spectrum of β-lactam antibiotics susceptible to hydrolysis by these enzymes. An increasing number of ESBLs not of TEM or SHV lineage have recently been described. The presence of ESBLs carries tremendous clinical significance. The ESBLs are frequently plasmid encoded. Plasmids responsible for ESBL production frequently carry genes encoding resistance to other drug classes (for example, aminoglycosides). Therefore, antibiotic options in the treatment of ESBL-producing organisms are extremely limited. Carbapenems are the treatment of choice for serious infections due to ESBL-producing organisms, yet carbapenem-resistant isolates have recently been reported. ESBL-producing organisms may appear susceptible to some extended-spectrum cephalosporins. However, treatment with such antibiotics has been associated with high failure rates. There is substantial debate as to the optimal method to prevent this occurrence. It has been proposed that cephalosporin breakpoints for the Enterobacteriaceae should be altered so that the need for ESBL detection would be obviated. At present, however, organizations such as the Clinical and Laboratory Standards Institute (formerly the National Committee for Clinical Laboratory Standards) provide guidelines for the detection of ESBLs in klebsiellae and Escherichia coli . In common to all ESBL detection methods is the general principle that the activity of extended-spectrum cephalosporins against ESBL-producing organisms will be enhanced by the presence of clavulanic acid. ESBLs represent an impressive example of the ability of gram-negative bacteria to develop new antibiotic resistance mechanisms in the face of the introduction of new antimicrobial agents.
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            Carbapenemases: the versatile beta-lactamases.

            Carbapenemases are beta-lactamases with versatile hydrolytic capacities. They have the ability to hydrolyze penicillins, cephalosporins, monobactams, and carbapenems. Bacteria producing these beta-lactamases may cause serious infections in which the carbapenemase activity renders many beta-lactams ineffective. Carbapenemases are members of the molecular class A, B, and D beta-lactamases. Class A and D enzymes have a serine-based hydrolytic mechanism, while class B enzymes are metallo-beta-lactamases that contain zinc in the active site. The class A carbapenemase group includes members of the SME, IMI, NMC, GES, and KPC families. Of these, the KPC carbapenemases are the most prevalent, found mostly on plasmids in Klebsiella pneumoniae. The class D carbapenemases consist of OXA-type beta-lactamases frequently detected in Acinetobacter baumannii. The metallo-beta-lactamases belong to the IMP, VIM, SPM, GIM, and SIM families and have been detected primarily in Pseudomonas aeruginosa; however, there are increasing numbers of reports worldwide of this group of beta-lactamases in the Enterobacteriaceae. This review updates the characteristics, epidemiology, and detection of the carbapenemases found in pathogenic bacteria.
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              Call of the wild: antibiotic resistance genes in natural environments.

              Antibiotic-resistant pathogens are profoundly important to human health, but the environmental reservoirs of resistance determinants are poorly understood. The origins of antibiotic resistance in the environment is relevant to human health because of the increasing importance of zoonotic diseases as well as the need for predicting emerging resistant pathogens. This Review explores the presence and spread of antibiotic resistance in non-agricultural, non-clinical environments and demonstrates the need for more intensive investigation on this subject.
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                Author and article information

                Journal
                Front Microbiol
                Front. Microbio.
                Frontiers in Microbiology
                Frontiers Research Foundation
                1664-302X
                28 September 2011
                2011
                : 2
                Affiliations
                1Laboratory for Zoonoses and Environmental Microbiology, Centre for Infectious Disease Control, National Institute of Public Health and the Environment Utrecht, Netherlands
                2Central Veterinary Institute of Wageningen UR Lelystad, Netherlands
                3Department of Infectious Diseases and Immunology, Utrecht University Utrecht, Netherlands
                4National Salmonella Reference Laboratory, Federal Institute for Risk Assessment Berlin, Germany
                5Department of Microbial Diseases, University College London Eastman Dental Institute, University College London London, UK
                Author notes

                Edited by: Timothy Rutland Walsh, Cardiff University, UK

                Reviewed by: M. Pilar Francino, Center for Public Health Research, Spain; Jun Liu, Mount Sinai School of Medicine, USA

                *Correspondence: Henk J. M. Aarts, National Institute of Public Health and the Environment, Antonie van Leeuwenhoekla 9, 3721 MA Bilthoven, Utrecht, Netherlands. e-mail: henk.aarts@ 123456rivm.nl

                This article was submitted to Frontiers in Antimicrobials, Resistance and Chemotherapy, a specialty of Frontiers in Microbiology.

                Article
                10.3389/fmicb.2011.00203
                3202223
                22046172
                Copyright © 2011 van Hoek, Mevius, Guerra, Mullany, Roberts and Aarts.

                This is an open-access article subject to a non-exclusive license between the authors and Frontiers Media SA, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and other Frontiers conditions are complied with.

                Page count
                Figures: 0, Tables: 7, Equations: 0, References: 185, Pages: 27, Words: 17254
                Categories
                Microbiology
                Review Article

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