transferability
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Atopy is excessive production of IgE in response to allergens. We evaluated in patients undergoing allogeneic hematopoietic cell transplantation (HCT) the following hypotheses: (1) Atopy is "curable" in atopic patients receiving HCT from a nonatopic donor (D-R+), and (2) Atopy is transferable from atopic donors to nonatopic recipients (D+R-). Atopic patients with atopic donors (D+R+) and non-atopic patients with non-atopic donors (D-R-) served as controls. We measured levels of multiallergen-specific IgE (A-IgE, atopy defined as ≥0.35 kUA/L) in sera from 54 patients and their donors pre HCT and from the patients at ≥2 years post HCT. Only 7/12 (58%) D- R+ patients became nonatopic after HCT. Only 1/11 (9%) D+R- patients became atopic. Eleven of 13 (85%) D-R- patients remained nonatopic. Unexpectedly, 11/18 (61%) D+R+ patients became nonatopic. In conclusion, contrary to our hypothesis and previous reports, the "cure" of atopy may occur in only some D-R+ patients and the transfer of atopy may occur rarely. The "cure" may not be necessarily due to the exchange of atopic for nonatopic immune system, as the "cure" may also occur in D+R+ patients.
- MeSH
- alergeny MeSH
- časná přecitlivělost * MeSH
- imunoglobulin E MeSH
- lidé MeSH
- transplantace hematopoetických kmenových buněk * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Přeruš. str. : il.
BACKGROUND: Conjugative plasmids play a major role in the dissemination of antibiotic resistance genes. Knowledge of the plasmid characteristics and behaviour can allow development of control strategies. Here we focus on the IncX group of plasmids carrying genes conferring quinolone resistance (PMQR), reporting their transfer and persistence within host bacteria of various genotypes under distinct conditions and levels of induced stress in form of temperature change and various concentrations of ciprofloxacin supplementation. METHODS: Complete nucleotide sequences were determined for eight qnr-carrying IncX-type plasmids, of IncX1 (3), IncX2 (3) and a hybrid IncX1-2 (2) types, recovered from Escherichia coli of various origins. This data was compared with further complete sequences of IncX1 and IncX2 plasmids carrying qnr genes (n = 41) retrieved from GenBank and phylogenetic tree was constructed. Representatives of IncX1 (pHP2) and IncX2 (p194) and their qnrS knockout mutants, were studied for influence of induced stress and genetic background on conjugative transfer and maintenance. RESULTS: A high level of IncX core-genome similarity was found in plasmids of animal, environmental and clinical origin. Significant differences were found between the individual IncX plasmids, with IncX1 subgroup plasmids showing higher conjugative transfer rates than IncX2 plasmids. Knockout of qnr modified transfer frequency of both plasmids. Two stresses applied simultaneously were needed to affect transfer rate of wildtype plasmids, whereas a single stress was sufficient to affect the IncX ΔqnrS plasmids. The conjugative transfer was shown to be biased towards the host phylogenetic proximity. A long-term cultivation experiment pointed out the persistence of IncX plasmids in the antibiotic-free environment. CONCLUSIONS: The study indicated the stimulating effect of ciprofloxacin supplementation on the plasmid transfer that can be nullified by the carriage of a single PMQR gene. The findings present the significant properties and behaviour of IncX plasmids carrying antibiotic resistance genes that are likely to play a role in their dissemination and stability in bacterial populations.
- MeSH
- antibakteriální látky farmakologie MeSH
- bakteriální léková rezistence genetika MeSH
- ciprofloxacin farmakologie MeSH
- Escherichia coli * genetika MeSH
- fylogeneze MeSH
- genomika MeSH
- konjugace genetická MeSH
- plazmidy genetika MeSH
- proteiny z Escherichia coli * genetika MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- MeSH
- antibakteriální látky farmakologie MeSH
- beta-laktamová rezistence genetika MeSH
- Enterobacter genetika izolace a purifikace účinky léků MeSH
- enterobakteriální infekce mikrobiologie MeSH
- konjugace genetická MeSH
- laktamy MeSH
- lidé MeSH
- mikrobiální testy citlivosti MeSH
- plazmidy genetika MeSH
- Check Tag
- lidé MeSH
Rezistencia gramnegativnych baktérií na beta-laktámové antibiotiká je spôsobovaná zväčša ich schopnosťou produkovať enzýmy, ktoré hydrolyzujú penicilíny, cefalosporíny, monobaktámy, prip. karbapenémy. Gény pre produkciu týchto enzýmov sú lokalizované extrachromozomálne na hľansferabilných plazmidoch, alebo sú súčasťou chromozomálnej DNA. V poslednom období nadmerné užívanie betalaktámových antibiotík a z toho vyplývajúci obrovský selekčný tlak najmä 3. generácie cefalosporínov, imipenemu a/alebo meropenemu spôsobuje nárast výskytu plazmidovo kódovaných tzv. Extended-Spectrum Beta-Lactamase (ESBL), chromozomálnej AmpC laktamázy a metalo-betalaktamáz. Producenti AmpC a/alebo metaloenzýmov sa prenášajú medzi pacientami, prip. pacientami a prostredím klonálne, takže tento proces môže byť obmedzený alebo prerušený preventívnymi opatreniami. Mutácie k produkcii ESBL a/alebo k nadprodukcii AmpC laktamázy sa vyskytujú v prípade masívnych bakteriálnych infekcií a sú selektované vysokým selekčným tlakom beta-laktámových antibiotík. Inhibítory beta-laktamáz blokujú produkciu ESBL, ako aj produkciu pôvodných TEM a SHV laktamáz a nie sú významnými induktormi produkcie enzýmu AmpC alebo metalo-enzýmov. Prevencia výskytu rezistencie na betalaktámové antibiotiká sa má uprednostniť pred následným riešením problémov, spôsobených rezistentnými baktériami.
Resistance of gramnegative bacteria to beta-lactam antibiotics is caused, in part, by their ability to produce enzymes which destroy the structure of penicillins, cephalosporins, monobactams and/or carbapenems. Genes for the production of these enzymes, called beta-lactamases, are coded either by extrachromosomal and transferable plasmids, or by chromosomal DNA. Recently, the selection pressure of a worldwide overuse of betalactam drugs, mostly, at present, of third-generation cephalosporins and of imipenem and/or meropenem, causes increased incidence of so-called Extended-Spectrum Beta-Lactamases (ESBL), which are plasmid-bome, of chromosomal AmpC lactamase, and of metallo-beta-lactamases. Producers of AmpC and/or metallo-enzymes are transmitted between patients and hospital environment by clonal spread. This process can be, thus, limited or interrupted by preventive measures. Mutations to production of ESBL and/or AmpC lactamases occur in massive inocula of bacteria and are selected by massive selection pressure by beta-lactams. Inhibitors of betalactamase(s) can block ESBL production, as well as the production of original TEM and SHV lactamases and are not significant inducers of AmpC or metallo-enzymes. In conclusion, prevention of emergence of resistance to beta-lactams is to be preferred to the solution of already emerged problems caused by resistant bacteria.
Recent advances in polarizable force fields have revealed that major reparameterization is necessary when the polarization energy is treated explicitly. This study is focused on the torsional parameters, which are crucial for the accurate description of conformational equilibria in biomolecules. In particular, attention is paid to the influence of polarization on the (i) transferability of dihedral terms between molecules, (ii) transferability between different environments, and (iii) additivity of dihedral energies. To this end, three polarizable force fields based on the induced point dipole model designed for use in AMBER are tested, including two recent ff02 reparameterizations. Attention is paid to the contributions due to short range interactions (1-2, 1-3, and 1-4) within the four atoms defining the dihedral angle. The results show that when short range 1-2 and 1-3 polarization interactions are omitted, as for instance in ff02, the 1-4 polarization contribution is rather small and unlikely to improve the description of the torsional energy. Conversely, when screened 1-2 and 1-3 interactions are included, the polarization contribution is sizeable and shows potential to improve the transferability of parameters between different molecules and environments as well as the additivity of dihedral terms. However, to reproduce intramolecular polarization effects accurately, further fine-tuning of the short range damping of polarization is necessary.
