Characterization of the chromosomal aac(6')-Ii gene specific for Enterococcus faecium

Costa, Yannick; Galimand, Marc; Leclercq, Roland; Duval, J; Courvalin, Patrice

doi:10.1128/aac.37.9.1896

Cited by 173 publications

(120 citation statements)

References 36 publications

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“…The BLAST results contain mostly GCN5-related N-acetyltransferases (GNAT) from different bacteria, with the top hit being an uncharacterized protein from Enterococcus faecium strain DO; therefore, we named this unknown gene YJM-GNAT. Some members of the GNAT superfamily are known to confer resistance to aminoglycoside antibiotics in certain bacteria, such as E. faecium (31,32) and Salmonella enterica (33). Furthermore, the phylogeny for YJM-GNAT differs dramatically from phylogenies obtained for other YJM789 genes (see Fig.…”

Section: Resultsmentioning

confidence: 91%

Genome sequencing and comparative analysis of Saccharomyces cerevisiae strain YJM789

McCusker

Hyman

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

243

291

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We sequenced the genome of Saccharomyces cerevisiae strain YJM789, which was derived from a yeast isolated from the lung of an AIDS patient with pneumonia. The strain is used for studies of fungal infections and quantitative genetics because of its extensive phenotypic differences to the laboratory reference strain, including growth at high temperature and deadly virulence in mouse models. Here we show that the Ϸ12-Mb genome of YJM789 contains Ϸ60,000 SNPs and Ϸ6,000 indels with respect to the reference S288c genome, leading to protein polymorphisms with a few known cases of phenotypic changes. Several ORFs are found to be unique to YJM789, some of which might have been acquired through horizontal transfer. Localized regions of high polymorphism density are scattered over the genome, in some cases spanning multiple ORFs and in others concentrated within single genes. The sequence of YJM789 contains clues to pathogenicity and spurs the development of more powerful approaches to dissecting the genetic basis of complex hereditary traits.comparative genomics ͉ genome architecture ͉ introgression ͉ lateral gene transfer T here is extensive genetic and phenotypic diversity within species. Determining which of the vast amounts of sequence differences that are found among individuals of a species contribute to heritable traits will allow diseases to be tackled at the molecular level and aid in the development of novel therapies. Saccharomyces cerevisiae, commonly known as baker's or brewer's yeast, plays a central role in food production and is one of the most studied genetic model species. It is not only widely used in biotechnology but also is a powerful model system that has been applied to identify multigenetic factors of hereditary traits (1-7). The genome sequence of one laboratory strain, a derivative of S288c, was the first genome of a free-living eukaryotic organism to be sequenced (8). Over the last 10 years, this genome has served as the reference for the S. cerevisiae species and has catalyzed the development of whole-genome approaches to biology (9, 10). Despite frequent laboratory use of alternative strains, sequence information for S. cerevisiae beyond the domesticated strain S288c has been fragmentary. S288c, which originated from a strain isolated from a rotten fig, was chosen for sequencing because it possesses properties that make it easy to work with, such as minimal colony morphology switching, consistent growth rates in glucose media, and no flocculence (11). At several loci, S288c contains polymorphisms not found in natural isolates, which could be hallmarks of domestication (12,13). A growing number of S. cerevisiae infections in humans have recently been reported (14). As a result, S. cerevisiae is also regarded as an emerging opportunistic pathogen that can cause clinically relevant infections in different patient types and body sites (15)(16)(17). One clinical strain (YJM145), derived from a yeast isolated from an AIDS patient with S. cerevisiae pneumonia (18), has been studied extensively as ...

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Section: Resultsmentioning

confidence: 91%

Genome sequencing and comparative analysis of Saccharomyces cerevisiae strain YJM789

McCusker

Hyman

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

243

291

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“…Integrons could "mop" up these genes following excision, and incorporate them into replicons, which could then be transferred among bacterial pathogens. Several pieces of evidence similarly support the hypothesis that housekeeping genes have evolved to modify antibiotics and that their recruitment could provide an alternate source of resistance genes [23,68]. All resistance-encoding DNAs establish a resistance gene pool, which represents a potential source of gene cassettes incorporated into the integrons [28].…”

Section: Mobile Gene Cassettesmentioning

confidence: 92%

Importance of integrons in the diffusion of resistance

2001

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Summary -Horizontal transfer of resistance genes is a successful mechanism for the transmission and dissemination of multiple drug resistance among bacterial pathogens. The impact of horizontally transmitted genetic determinants in the evolution of resistance is particularly evident when resistance genes are physically associated in clusters and transferred en bloc to the recipient cell. Recent advances in the molecular characterisation of antibiotic resistance mechanisms have highlighted the existence of genetic structures, called integrons, involved in the acquisition of resistance genes. These DNA elements have frequently been reported in multi-drug resistant strains isolated from animals and humans, and are located either on the bacterial chromosome or on broad-host-range plasmids. The role of integrons in the development of multiple resistance relies on their unique capacity to cluster and express drug resistance genes. Moreover, the spread of resistance genes among different replicons and their exchange between plasmid and bacterial chromosome are facilitated by the integration of integrons into transposable elements. The association of a highly efficient gene capture and expression system, together with the capacity for vertical and horizontal transmission of resistance genes represents a powerful weapon used by bacteria to combat the assault of antibiotics. antimicrobial resistance / integron / transposon / horizontal gene transferRésumé -Importance des intégrons dans la diffusion de la résistance. Le transfert horizontal de gènes est un mécanisme efficace pour la transmission et la dissémination, parmi les agents pathogènes bactériens, de résistances multiples aux antibiotiques. L'impact des déterminants génétiques transmis horizontalement dans l'évolution de la résistance est particulièrement évident lorsque les gènes de résistance sont physiquement regroupés, et transférés en bloc à la cellule réceptrice. Des avancées récentes dans la caractérisation moléculaire des mécanismes de résistance aux antibiotiques ont mis en évidence l'existence de structures génétiques, appelées intégrons, impliqués dans l'acquisition de gènes de résistance. Ces éléments d'ADN ont été fréquemment observés dans des souches bactériennes multi-résistantes isolées chez des animaux ou chez des humains, localisés soit sur le chromosome bactérien, soit sur des plasmides à large spectre d'hôte. Le rôle des intégrons dans le développement de la multi-résistance repose sur leur capacité unique à former des clusters de gènes et à exprimer des gènes Vet. Res. 32 (2001) 243-259 243

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“…• the chromosomal gene aac(6')-Ii, which encodes for a 6´-N-aminoglycoside acetyltransferase (Moellering et al, 1979;Costa et al 1993). Regarding the comment on amikacin resistance, raised in paragraph 7, it is reported that aac(6')-Ii does not confer high-level resistance to amikacin in E. faecium (Moellering, 1979).…”

Section: Intrinsic Resistancementioning

confidence: 99%

“…Regarding the comment on amikacin resistance, raised in paragraph 7, it is reported that aac(6')-Ii does not confer high-level resistance to amikacin in E. faecium (Moellering, 1979). A linkage between this gene and amikacin resistance has been observed only in E. coli when aac(6')-Ii is over-expressed, being harboured by a multicopy plasmid (Costa et al, 1993); and…”

Section: Intrinsic Resistancementioning

confidence: 99%

Statement on the assessment of the safety of Cylactin® (Enterococcus faecium) used in animal nutrition

Mézes¹

2010

EFS2

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SUMMARYThe European Food Safety Authority (EFSA) published a Scientific Opinion on the safety and efficacy of the product Cylactin ® (Enterococcus faecium) as a feed additive for chickens for fattening. In that opinion, the Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) The European Commission requested EFSA to evaluate the comments raised by the Austrian Authorities thereof during a meeting of the Standing Committee. The Austrian Authorities presented their concerns under eight key points; five of those regarded fundamental statements relating to the use of antibiotics and developing resistance amongst bacteria, which are shared by the FEEDAP Panel.The potential for horizontal gene transfer amongst bacteria is the basis for all the FEEDAP Panel assessments of bacterial additives safety. Consequently, the assessment of Cylactin ® , being related to antibiotic resistance, followed the approach documented in the relevant Technical Guidance document prepared by the FEEDAP Panel; in this case, it focused on kanamycin resistance.The minimum inhibitory concentration of E. faecium NCIMB 10415 for kanamycin was found to be higher than the breakpoint identified by the FEEDAP Panel, which triggered a need for the determination of the genetic nature of this resistance.Bioinformatic analyses of the genome sequence of E. faecium NCIMB 10415 demonstrated that none of the known genes coding for high-level aminoglycoside resistance were present. The available evidence demonstrated that the low level resistance to kanamycin shown by this strain of E. faecium results from the presence of two chromosomal genes (aac(6')-Ii and efmM, synonymous with sfkm r ), which are intrinsic to all E. faecium strains studied to date. Gene inactivation experiments conducted with this strain confirmed that no other genetic determinants of resistance to kanamycin were involved. The gene aac(6')-Ii does not confer high-level resistance to amikacin in E. faecium.The FEEDAP Panel reiterates its former conclusions that: (i) the genetic determinants conferring kanamycin resistance to E. faecium NCIMB 10415 are intrinsic to E. faecium, (ii) the risk of horizontal transfer of these genes is minimal, and (iii) the use of Cylactin ® in animal nutrition would not increase the prevalence of aac(6')-Ii and efmM genes in the environment.

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Characterization of the chromosomal aac(6')-Ii gene specific for Enterococcus faecium

Cited by 173 publications

References 36 publications

Genome sequencing and comparative analysis of Saccharomyces cerevisiae strain YJM789

Genome sequencing and comparative analysis of Saccharomyces cerevisiae strain YJM789

Importance of integrons in the diffusion of resistance

Statement on the assessment of the safety of Cylactin® (Enterococcus faecium) used in animal nutrition

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