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      Dissemination of Clonally Related Escherichia coli Strains Expressing Extended-Spectrum β-Lactamase CTX-M-15

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          Abstract

          E. coli ST131 and ST405 and multidrug-resistant IncFII plasmids may determine spread of this lactamase.

          Abstract

          We analyzed 43 CTX-M-15–producing Escherichia coli isolates and 6 plasmids encoding the bla CTX-M-15 gene from Canada, India, Kuwait, France, Switzerland, Portugal, and Spain. Most isolates belonged to phylogroups B2 (50%) and D (25%). An EC-B2 strain of clonal complex sequence type (ST) 131 was detected in all countries; other B2 isolates corresponded to ST28, ST405, ST354, and ST695 from specific areas. EC-D strains were clonally unrelated but isolates from 3 countries belonged to ST405. All CTX-M-15 plasmids corresponded to IncFII group with overrepresentation of 3 HpaI-digested plasmid DNA profiles (A, B and C; 85–120kb, similarity >70%). Plasmid A was detected in EC -B2 strains (ST131, ST354, or ST405), plasmid C was detected in B2 and D strains, and plasmid B was confined to worldwide-disseminated ST131. Most plasmids contained bla OXA-1, aac(6′)-Ib-cr, and bla TEM-1. Worldwide dissemination of CTX-M-15 seems to be determined by clonal complexes ST131 and ST405 and multidrug-resistant IncFII plasmids.

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          Most cited references30

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          Fluoroquinolone-modifying enzyme: a new adaptation of a common aminoglycoside acetyltransferase.

          Antimicrobial-modifying resistance enzymes have traditionally been class specific, having coevolved with the antibiotics they inactivate. Fluoroquinolones, antimicrobial agents used extensively in medicine and agriculture, are synthetic and have been considered safe from naturally occurring antimicrobial-modifying enzymes. We describe reduced susceptibility to ciprofloxacin in clinical bacterial isolates conferred by a variant of the gene encoding aminoglycoside acetyltransferase AAC(6')-Ib. This enzyme reduces the activity of ciprofloxacin by N-acetylation at the amino nitrogen on its piperazinyl substituent. Although approximately 30 variants of this gene have been reported since 1986, the two base-pair changes responsible for the ciprofloxacin modification phenotype are unique to this variant, first reported in 2003 and now widely disseminated. An intense increase in the medical use of ciprofloxacin seems to have been accompanied by a notable development: a single-function resistance enzyme has crossed class boundaries, and is now capable of enzymatically undermining two unrelated antimicrobial agents, one of them fully synthetic.
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            CTX-M: changing the face of ESBLs in Europe.

            Since around 2000 - earlier in Poland and Spain and later in France and the UK - dramatic shifts have occurred in the prevalence and types of extended-spectrum beta-lactamases (ESBLs) in Europe. Before this watershed, most producers were nosocomial isolates, often Klebsiella spp. or Enterobacter spp. from specialist care units, and had mutant TEM or SHV ESBLs. Subsequently, CTX-M ESBLs have become dominant, with much greater penetration into Escherichia coli, and with many infections in 'complicated community' patients, usually with underlying disease, recent antibiotic usage, or healthcare contact. The degree of clonality among producers varies with the country, as does the enzyme type produced, with group 9 (CTX-M-9 and -14) enzymes dominant in Spain and group 1 enzymes (particularly CTX-M-3 and -15) dominant elsewhere. Irrespective of the particular enzyme, most producers are multiresistant. These changing patterns present major therapeutic and infection control challenges, with the public health intervention points unclear.
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              Natural selection, infectious transfer and the existence conditions for bacterial plasmids.

              Despite the near-ubiquity of plasmids in bacterial populations and the profound contribution of infectious gene transfer to the adaptation and evolution of bacteria, the mechanisms responsible for the maintenance of plasmids in bacterial populations are poorly understood. In this article, we address the question of how plasmids manage to persist over evolutionary time. Empirical studies suggest that plasmids are not infectiously transmitted at a rate high enough to be maintained as genetic parasites. In part i, we present a general mathematical proof that if this is the case, then plasmids will not be able to persist indefinitely solely by carrying genes that are beneficial or sometimes beneficial to their host bacteria. Instead, such genes should, in the long run, be incorporated into the bacterial chromosome. If the mobility of host-adaptive genes imposes a cost, that mobility will eventually be lost. In part ii, we illustrate a pair of mechanisms by which plasmids can be maintained indefinitely even when their rates of transmission are too low for them to be genetic parasites. First, plasmids may persist because they can transfer locally adapted genes to newly arriving strains bearing evolutionary innovations, and thereby preserve the local adaptations in the face of background selective sweeps. Second, plasmids may persist because of their ability to shuttle intermittently favored genes back and forth between various (noncompeting) bacterial strains, ecotypes, or even species.
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                Author and article information

                Journal
                Emerg Infect Dis
                EID
                Emerging Infectious Diseases
                Centers for Disease Control and Prevention
                1080-6040
                1080-6059
                February 2008
                : 14
                : 2
                : 195-200
                Affiliations
                [* ]Hospital Universitario Ramón y Cajal, Madrid, Spain
                []Unidad de Resistencia a Antibióticos y Virulencia Bacteriana Asociada al Consejo Superior de Investigaciones Científicas, Madrid, Spain
                []El Consorcio de Investigación Biomédica en Red de Epidemiología y Salud Pública, Madrid, Spain
                [ § ]Istituto Superiore di Sanità, Rome, Italy
                []Hospital Bicetre, Paris, France
                [# ]Calgary Laboratory Services, Calgary, Alberta, Canada
                [** ]University of Calgary, Calgary, Alberta, Canada
                [†† ]Universidade do Porto, Porto, Portugal
                Author notes
                Address for correspondence: Teresa M. Coque, Servicio de Microbiología, Hospital Universitario Ramón y Cajal, Carretera de Colmenar, Km 9, Madrid 28034, Spain; email: mcoque.hrc@ 123456salud.madrid.org
                Article
                07-0350
                10.3201/eid1402.070350
                2600198
                18258110
                50d167e3-87ba-4b5f-bc24-1b5616dc3808
                History
                Categories
                Research

                Infectious disease & Microbiology
                phylogenetic group b2,phylogenetic group d,research,escherichia coli,ctx-m-15,incfii plasmids,extended-spectrum β-lactamase

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