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ABSTRACT: Increased expression of chromosomal genes for resistance-nodulation-division (RND) type efflux systems plays a major role in multidrug resistance (MDR) of Acinetobacter baunannii. However, the relative contribution of the three most prevalent pumps, AdeABC, AdeFGH, and AdeIJK has not been evaluated in clinical settings. We have screened fourteen MDR clinical isolates, distinct on the basis of MLST and PFGE, for the presence and overexpression of the three Ade efflux systems and analysed the sequence of the regulators AdeRS two-component for AdeABC, LysR-type AdeL for AdeFGH. Gene adeB was detected in 13 out of 14 isolates, adeG and instrinsic adeJ in all strains. Significant overexpresssion of adeB was observed in 10 strains whereas only 7 had moderately increased levels of expression of AdeFGH, and none overexpressed AdeIJK. Thirteen strains had reduced susceptibility to tigecycline but there was no correlation between tigecycline MICs and the levels of AdeABC expression suggesting other mechanisms for tigecycline resistance. No mutations were found in the highly conserved AdeN regulator of the nine strains expressing AdeFGH. In contrast, functional mutations were found in conserved domains of AdeRS in all the strains that overexpressed AdeABC with two mutational hot spots, one in AdeS near histidine 149 suggesting convergent evolution and the other in the DNA binding domain of AdeR compatible with horizontal gene transfer. This study outlines the high incidence of AdeABC efflux pump overexpression in MDR A. baumannii as a result of a variety of single mutations in the correponding two-component regulatory system.
Antimicrobial Agents and Chemotherapy 04/2013; · 4.84 Impact Factor
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ABSTRACT: D-alanyl:D-lactate and D-alanyl:D-serine ligases are key enzymes in vancomycin resistance of Gram-positive cocci. They catalyze a critical step in the synthesis of modified peptidoglycan precursors which are low binding affinity targets for vancomycin. The structure of the D-Ala:D-Lac ligase VanA led to the understanding of the molecular basis for its specificity but that of D-Ala:D-Ser ligases has not been determined. We have investigated the enzymatic kinetics of the D-Ala:D-Ser ligase VanG from Enterococcus faecalis and solved its crystal structure in complex with ADP. The overall structure of VanG is similar to that of VanA but has significant differences mainly in the N-terminal and central domains. Based on reported mutagenesis data and comparison of the VanG and VanA structures, we show that residues D243, F252, and R324 are molecular determinants for D-Ser selectivity. These residues are conserved in both enzymes and explain why VanA also displays D-Ala:D-Ser ligase activity, albeit with low catalytic efficiency in comparison to VanG. These observations suggest that D-Ala:D-Lac and D-Ala:D-Ser enzymes have evolved from a common ancestral D-Ala:D-X ligase. The crystal structure of VanG showed an unusual interaction between two dimers involving residues of the omega loop that are deeply anchored in the active site. We constructed an octapeptide mimicking the omega loop and found that it selectively inhibits VanG and VanA but not Staphylococcus aureus D-Ala:D-Ala ligase. This study provides additional insight into the molecular evolution of D-Ala:D-X ligases and could contribute to the development of new structure-based inhibitors of vancomycin resistance enzymes.
Journal of Biological Chemistry 09/2012; · 4.77 Impact Factor
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ABSTRACT: Vancomycin-resistant Staphylococcus aureus VRSA-10 was isolated in 2009, whereas VRSA-11A and VRSA-11B were isolated from the same patient in 2010. Growth curves and determination of the nature of the peptidoglycan precursors and of the VanX d,d-dipeptidase activity in the absence and in the presence of vancomycin indicated that vancomycin resistance was inducible in VRSA-10, that VRSA-11A was partially dependent on glycopeptide for growth, and that VRSA-11B was constitutively resistant. Both VRSA-11A and -11B harbored an insertion sequence, ISEf1, at the same locus in the vanX-vanY intergenic region of Tn1546 and an S(183)A mutation in the chromosomal d-alanyl:d-alanine ligase (Ddl). This substitution has been shown to be responsible for a drastic diminution of the affinity of the enzyme for d-Ala at subsite 1 in Escherichia coli DdlB. VRSA-11B exhibited an additional mutation, P(216)T, in the transcriptional regulator VanR, most probably associated with constitutive expression of vancomycin resistance. It is thus likely that VRSA-11B is a constitutive derivative of VRSA-11A selected during prolonged vancomycin therapy. Synthesis of peptidoglycan precursors ending in d-Ala-d-lactate was responsible for oxacillin susceptibility of VRSA-11A and VRSA-11B despite the presence of a wild-type mecA gene in both strains.
Antimicrobial Agents and Chemotherapy 06/2012; 56(9):4693-6. · 4.84 Impact Factor
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ABSTRACT: Multidrug-resistant clinical isolate Klebsiella pneumoniae BM4686 was highly resistant to 4,6-disubstituted 2-deoxystreptamines and to fortimicin. Resistance was due to the presence, on the 40-kb non-self-transferable plasmid pIP849, of the rmtF gene which was cotranscribed with the upstream aac(6')-Ib gene. The deduced RmtF protein had 25 to 46% identity with members of the N7 G1405 family of aminoglycoside resistance 16S rRNA methyltransferases.
Antimicrobial Agents and Chemotherapy 04/2012; 56(7):3960-2. · 4.84 Impact Factor
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ABSTRACT: Resistance-nodulation-division efflux system AdeIJK contributes to intrinsic resistance to various drug classes in Acinetobacter baumannii. By whole-genome sequencing, we have identified in clinical isolate BM4587 the adeN gene, located 813 kbp upstream from adeIJK, which encodes a TetR transcriptional regulator. In one-step mutant BM4666 overexpressing adeIJK, the deletion of cytosine 582 (C(582)) in the 3' portion of this gene was responsible for a frameshift mutation resulting in the deletion of the seven C-terminal residues. trans-Complementation of this BM4587 derivative with a plasmid expressing adeN restored antibiotic susceptibility to the host associated with the loss of adeJ overexpression. The inactivation of adeN in BM4587 led to a diminished susceptibility to antibiotics that are substrates for AdeIJK and to a 5-fold increase in adeJ expression. Taken together, these results indicate that AdeN represses AdeIJK expression. Quantitative reverse transcription-PCR (qRT-PCR) demonstrated that AdeN is constitutively expressed in BM4587 and does not regulate its own expression. Deletion of cytosine 582 and a 394-bp deletion of the 3' part of adeN were found in independent one-step adeIJK-overexpressing mutants selected from clinical isolates BM4667 and BM4651, respectively. The corresponding alterations were located in the α9 helix, which is known to be involved in dimerization, a process essential for the activity of TetR regulators. The adeN gene was detected in all of the 30 A. baumannii strains tested and in Acinetobacter calcoaceticus, Acinetobacter nosocomialis, and Acinetobacter pittii.
Antimicrobial Agents and Chemotherapy 02/2012; 56(5):2504-10. · 4.84 Impact Factor
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ABSTRACT: Enterococcus faecium UCN71, isolated from a blood culture, was resistant to low levels of vancomycin (MIC, 16 μg/ml) but susceptible to teicoplanin (MIC, 0.5 μg/ml). No amplification was observed with primers specific for the previously described glycopeptide resistance ligase genes, but a PCR product corresponding to a gene called vanN was obtained using degenerate primers and was sequenced. The deduced VanN protein was related (65% identity) to the d-alanine:d-serine VanL ligase. The organization of the vanN gene cluster, determined using degenerate primers and by thermal asymmetric interlaced (TAIL)-PCR, was similar to that of the vanC operons. A single promoter upstream from the resistance operon was identified by rapid amplification of cDNA ends (RACE)-PCR. The presence of peptidoglycan precursors ending in d-serine and d,d-peptidase activities in the absence of vancomycin indicated constitutive expression of the resistance operon. VanN-type resistance was transferable by conjugation to E. faecium. This is the first report of transferable d-Ala-d-Ser-type resistance in E. faecium.
Antimicrobial Agents and Chemotherapy 08/2011; 55(10):4606-12. · 4.84 Impact Factor
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ABSTRACT: To describe a novel extended-spectrum oxacillinase, named OXA-145, differing from narrow-spectrum OXA-35 (from the OXA-10 group) by deletion of residue Leu-165. The genetic environment of bla(OXA-145) and the biochemical properties of OXA-145 are reported. We also assessed the impact of the Leu-165 deletion on the hydrolysis spectrum of the ancestor OXA-10.
Extended-spectrum β-lactamase OXA-145 was identified in the multidrug-resistant clinical Pseudomonas aeruginosa 08-056, and characterized by isoelectric focusing, PCR and DNA sequencing. Antibiotic susceptibility tests were performed by agar dilution. The resistance profiles conferred by cloned bla(OXA-10), bla(OXA-35), bla(OXA-145) and a bla(OXA-10) derivative obtained by site-directed mutagenesis were determined in Escherichia coli. Kinetic parameters of OXA-35 and OXA-145 were established after purification of His-tagged proteins.
The sequence of OXA-145, encoded by a class 1 integron-borne gene in strain 08-056, differed from that of narrow-spectrum penicillinase OXA-35 by a single amino acid deletion (Leu-165) located in the highly conserved omega loop. Deletion of Leu-165 from OXA-35 (yielding OXA-145) or OXA-10 (the progenitor of OXA-35) extended the hydrolysis spectrum to third-generation cephalosporins and to monobactams, while reducing that for penicillins. OXA-145 showed biphasic hydrolysis curves for all the substrates tested. Its activity against nitrocefin was 10-fold higher in the presence of sodium hydrogen carbonate.
OXA-145 is a new extended-spectrum β-lactamase from the OXA-10 group. The deletion of Leu-165 is responsible for a shift in the hydrolysis spectrum from penicillins to third-generation cephalosporins, as well as monobactams. The loss of penicillin hydrolysis was due to a non-carboxylated Lys-73.
Journal of Antimicrobial Chemotherapy 06/2011; 66(8):1745-50. · 5.07 Impact Factor
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ABSTRACT: Aminoglycosides are ribosome-targeting antibiotics and a major drug group of choice in the treatment of serious enterococcal infections. Here we show that aminoglycoside resistance in Enterococcus faecium strain CIP 54-32 is conferred by the chromosomal gene efmM, encoding the E. faecium methyltransferase, as well as by the previously characterized aac(6')-Ii that encodes a 6'-N-aminoglycoside acetyltransferase. Inactivation of efmM in E. faecium increases susceptibility to the aminoglycosides kanamycin and tobramycin, and, conversely, expression of a recombinant version of efmM in Escherichia coli confers resistance to these drugs. The EfmM protein shows significant sequence similarity to E. coli RsmF (previously called YebU), which is a 5-methylcytidine (m⁵C) methyltransferase modifying 16S rRNA nucleotide C1407. The target for EfmM is shown by mass spectrometry to be a neighboring 16S rRNA nucleotide at C1404. EfmM uses the methyl group donor S-adenosyl-L-methionine to catalyze formation of m⁵C1404 on the 30S ribosomal subunit, whereas naked 16S rRNA and the 70S ribosome are not substrates. Addition of the 5-methyl to C1404 sterically hinders aminoglycoside binding. Crystallographic structure determination of EfmM at 2.28 Å resolution reveals an N-terminal domain connected to a central methyltransferase domain that is linked by a flexible lysine-rich region to two C-terminal subdomains. Mutagenesis of the methyltransferase domain established that two cysteines at specific tertiary locations are required for catalysis. The tertiary structure of EfmM is highly similar to that of RsmF, consistent with m⁵C formation at adjacent sites on the 30S subunit, while distinctive structural features account for the enzymes' respective specificities for nucleotides C1404 and C1407.
RNA 02/2011; 17(2):251-62. · 5.09 Impact Factor
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ABSTRACT: In order to assess antimicrobial resistance in Listeria monocytogenes, 202 food and environmental isolates from 1996 to 2006 were tested. Only four strains displayed acquired resistance. Resistance to erythromycin, tetracycline-minocycline, and trimethoprim was evidenced, and the genes erm(B), tet(M), and dfrD, already found in L. monocytogenes, were detected.
Applied and environmental microbiology 02/2011; 77(8):2788-90. · 3.69 Impact Factor
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ABSTRACT: Among Acinetobacter spp., A. baumannii is the most frequently implicated in nosocomial infections, in particular in intensive care units. It was initially thought that multidrug resistance (MDR) in this species was due mainly to horizontal acquisition of resistance genes. However, it has recently become obvious that increased expression of chromosomal genes for efflux systems plays a major role in MDR. Among the five superfamilies of pumps, resistance-nodulation-division (RND) systems are the most prevalent in multiply resistant A. baumannii. RND pumps typically exhibit a wide substrate range that can include antibiotics, dyes, biocides, detergents, and antiseptics. Overexpression of AdeABC, secondary to mutations in the adeRS genes encoding a two-component regulatory system, constitutes a major mechanism of multiresistance in A. baumannii. AdeIJK, intrinsic to this species, is responsible for natural resistance, but since overexpression above a certain threshold is toxic for the host, its contribution to acquired resistance is minimal. The recently described AdeFGH, probably regulated by a LysR-type transcriptional regulator, also confers multidrug resistance when overexpressed. Non-RND efflux systems, such as CraA, AmvA, AbeM, and AbeS, have also been characterized for A. baumannii, as have AdeXYZ and AdeDE for other Acinetobacter spp. Finally, acquired narrow-spectrum efflux pumps, such as the major facilitator superfamily (MFS) members TetA, TetB, CmlA, and FloR and the small multidrug resistance (SMR) member QacE in Acinetobacter spp., have been detected and are mainly encoded by mobile genetic elements.
Antimicrobial Agents and Chemotherapy 12/2010; 55(3):947-53. · 4.84 Impact Factor
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ABSTRACT: We have assessed the performance of semi-automated rep-PCR (Diversilab®) and multilocus sequence typing (MLST) in comparison to pulsed-field gel electrophoresis (PFGE) for typing a collection of 29 epidemiologically characterized vancomycin-resistant Enterococcus faecium (VRE). Sixteen strains that harbored the Tn1546 element were typed by PCR mapping. The discriminative power of the typing methods was calculated by the Simpson's index of diversity, and the concordance between methods was evaluated by the Kendall's coefficient of concordance. Semi-automated rep-PCR appeared as discriminative as PFGE and was further compared with PFGE for typing 67 VRE isolated during a hospital outbreak. Rep-PCR appeared to be more discriminative than PFGE for this second set of strains. Reproducibility of DiversiLab® was also tested against 35 selected isolates. Only three showed less than 97% similarity, indicating high reproducibility at this level of discrimination. In conclusion, semi-automated rep-PCR is a useful tool for rapid screening of VRE isolates during an outbreak, although cost of the system may be limiting for routine implementation. PFGE, which remains the reference method, should be used for confirmation and evaluation of the genetic relatedness of epidemic isolates.
Journal of microbiological methods 11/2010; 84(1):74-80. · 2.43 Impact Factor
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ABSTRACT: Acinetobacter baumannii is a major nosocomial pathogen which frequently develops multidrug resistance by acquisition of antibiotic resistance genes and overexpression of intrinsic efflux systems, such as the RND efflux pumps AdeABC and AdeIJK. A third RND system was characterized by studying spontaneous mutants BM4663 and BM4664, which were selected in the presence of chloramphenicol and norfloxacin, respectively, from the AdeABC- and AdeIJK-defective derivative A. baumannii BM4652. They exhibited enhanced resistance to fluoroquinolones, tetracycline-tigecycline, chloramphenicol, clindamycin, trimethoprim, sulfamethoxazole, sodium dodecyl sulfate, and dyes such as ethidium bromide, safranin O, and acridine orange. Comparison of transcriptomes of mutants with that of their parental strain, using a microarray technology, demonstrated the overexpression of three genes that encoded an RND efflux system, named AdeFGH. Inactivation of AdeFGH in BM4664 restored an antibiotic susceptibility profile identical to that of BM4652, indicating that AdeFGH was cryptic in BM4652 and responsible for multidrug resistance in its mutants. RNA analysis demonstrated that the three genes were cotranscribed. The adeFGH operon was found in 36 out of 40 A. baumannii clinical isolates, but none of the 22 isolates tested overexpressed the pump genes. Spontaneous MDR mutant BM4684, overexpressing adeFGH, was obtained from clinical isolate BM4587, indicating that adeFGH can be overexpressed in a strain harboring adeABC-adeIJK. An open reading frame, coding a LysR-type transcriptional regulator, named adeL, was located upstream from the adeFGH operon and transcribed in the opposite direction. Mutations in adeL were found in the three adeFGH-overexpressing mutants, suggesting that they were responsible for overexpression of AdeFGH.
Antimicrobial Agents and Chemotherapy 10/2010; 54(10):4389-93. · 4.84 Impact Factor
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ABSTRACT: The vancomycin-resistant Staphylococcus aureus VRSA-9 clinical isolate was partially dependent on glycopeptide for growth. The responsible vanA operon had the same organization as that of Tn1546 and was located on a plasmid. The chromosomal D-Ala:D-Ala ligase (ddl) gene had two point mutations that led to Q260K and A283E substitutions, resulting in a 200-fold decrease in enzymatic activity compared to that of the wild-type strain VRSA-6. To gain insight into the mechanism of enzyme impairment, we determined the crystal structure of VRSA-9 Ddl and showed that the A283E mutation induces new ion pair/hydrogen bond interactions, leading to an asymmetric rearrangement of side chains in the dimer interface. The Q260K substitution is located in an exposed external loop and did not induce any significant conformational change. The VRSA-9 strain was susceptible to oxacillin due to synthesis of pentadepsipeptide precursors ending in D-alanyl-D-lactate which are not substrates for the β-lactam-resistant penicillin binding protein PBP2'. Comparison with the partially vancomycin-dependent VRSA-7, whose Ddl is 5-fold less efficient than that of VRSA-9, indicated that the levels of vancomycin dependence and susceptibility to β-lactams correlate with the degree of Ddl impairment. Ddl drug targeting could therefore be an effective strategy against vancomycin-resistant S. aureus.
Journal of bacteriology 10/2010; 192(20):5465-71. · 3.94 Impact Factor
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ABSTRACT: Inducible vancomycin resistance in enterococci is due to a sophisticated mechanism that combines synthesis of cell wall peptidoglycan precursors with low affinity for glycopeptides and elimination of the normal target precursors. Although this dual mechanism, which involves seven genes organized in two operons, is predicted to have a high fitness cost, resistant enterococci have disseminated worldwide. We have evaluated the biological cost of VanB-type resistance due to acquisition of conjugative transposon Tn1549 in Enterococcus faecium and Enterococcus faecalis. Because fitness was dependent on the integration site of Tn1549, an isogenic set of E. faecalis was constructed to determine the cost of inducible or constitutive expression of resistance or of carriage of Tn1549. A luciferase gene was inserted in the integrase gene of the transposon to allow differential quantification of the strains in cocultures and in the digestive tract of gnotobiotic mice. Both in vitro and in vivo, carriage of inactivated or inducible Tn1549 had no cost for the host in the absence of induction by vancomycin. In contrast, induced or constitutively resistant strains not only had reduced fitness but were severely impaired in colonization ability and dissemination among mice. These data indicate that tight regulation of resistance expression drastically reduces the biological cost associated with vancomycin resistance in Enterococcus spp. and accounts for the widespread dissemination of these strains. Our findings are in agreement with the observation that regulation of expression is common in horizontally acquired resistance and represents an efficient evolutionary pathway for resistance determinants to become selectively neutral.
Proceedings of the National Academy of Sciences 09/2010; 107(39):16964-9. · 9.68 Impact Factor
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ABSTRACT: Rahnella aquatilis is an environmental enterobacterial species with a chromosomal bla(RAHN-1) gene encoding extended-spectrum class A beta-lactamase RAHN-1. We describe the diversity of bla(RAHN) genes from two groups of strains, G1 and G2, isolated from raw fruits and vegetables, and the new class A beta-lactamase RAHN-2.
MICs were determined by Etest. bla(RAHN) genes were amplified by PCR, sequenced, and cloned to produce RAHN-1 and RAHN-2 proteins whose kinetic parameters were determined.
All strains had similar beta-lactam resistance patterns. However, isolates of G1 were at least 2-fold more susceptible to piperacillin, amoxicillin, piperacillin/clavulanic acid, piperacillin/tazobactam and cefotaxime. Sequences of bla(RAHN) from G1 had <82.9% identity with that of bla(RAHN-1), whereas those of G2 were >92% identical. The RAHN-2 beta-lactamase was 89.8% identical to RAHN-1, 5-fold more efficient than RAHN-1 in hydrolysing ticarcillin and 2.5-fold more efficient in cefotaxime and cefuroxime hydrolysis. However, the specific activity of RAHN-1 was 2-fold higher than that of RAHN-2 suggesting that the bla(RAHN) genes are regulated differently.
The new class A beta-lactamase RAHN-2 is phenotypically difficult to detect and requires MIC determination.
Journal of Antimicrobial Chemotherapy 08/2010; 65(8):1619-23. · 5.07 Impact Factor
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Clinical Infectious Diseases 05/2010; 50(10):1429-31. · 9.15 Impact Factor
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ABSTRACT: Pseudomonas aeruginosa is a major human opportunistic pathogen, especially for patients in intensive care units or with cystic fibrosis. Multidrug resistance is a common feature of this species. In a previous study we detected the ant(4')-IIb gene in six multiresistant clinical isolates of P. aeruginosa, and determination of the environment of the gene led to characterization of Tn6061. This 26 586 bp element, a member of the Tn3 family of transposons, carried 10 genes conferring resistance to six drug classes. The ant(4')-IIb sequence was flanked by directly repeated copies of ISCR6 in all but one of the strains studied, consistent with ISCR6-mediated gene acquisition. Tn6061 was chromosomally located in six strains and plasmid-borne in the remaining isolate, suggesting horizontal acquisition. Duplication-insertion of IS6100, that ended Tn6061, was responsible for large chromosomal inversions. Acquisition of Tn6061 and chromosomal inversions are further examples of intricate mechanisms that contribute to the genome plasticity of P. aeruginosa.
Microbiology 05/2010; 156(Pt 5):1448-58. · 3.06 Impact Factor
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ABSTRACT: An oligonucleotide-based DNA microarray was developed to evaluate expression of genes for efflux pumps in Acinetobacter baumannii and to detect acquired antibiotic resistance determinants. The microarray contained probes for 205 genes, including those for 47 efflux systems, 55 resistance determinants, and 35 housekeeping genes. The microarray was validated by comparative analysis of mutants overexpressing or deficient in the pumps relative to the parental strain. The performance of the microarray was also evaluated using in vitro single-step mutants obtained on various antibiotics. Overexpression, confirmed by quantitative reverse transcriptase PCR, of RND efflux pumps AdeABC, due to a G30D substitution in AdeS in a multidrug-resistant (MDR) strain obtained on gentamicin, and AdeIJK, in two mutants obtained on cefotaxime or tetracycline, was detected. A new efflux pump, AdeFGH, was found to be overexpressed in a mutant obtained on chloramphenicol. Study of MDR clinical isolates, including the AYE strain, whose entire sequence has been determined, indicated overexpression of AdeABC and of the chromosomally encoded cephalosporinase as well as the presence of several acquired resistance genes. The overexpressed and acquired determinants detected by the microarray could account for nearly the entire MDR phenotype of the isolates. The microarray is potentially useful for detection of resistance in A. baumannii and should allow detection of new efflux systems associated with antibiotic resistance.
Antimicrobial Agents and Chemotherapy 11/2009; 54(1):333-40. · 4.84 Impact Factor
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Raymond Ruimy,
Anne Brisabois,
Claire Bernede,
David Skurnik,
Saïda Barnat,
Guillaume Arlet,
Sonia Momcilovic,
Sandrine Elbaz,
Frédérique Moury,
Marie-Anne Vibet, Patrice Courvalin,
Didier Guillemot,
Antoine Andremont
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ABSTRACT: Resistance to antibiotics is a major public health problem which might culminate in outbreaks caused by pathogenic bacteria untreatable by known antibiotics. Most of the genes conferring resistance are acquired horizontally from already resistant commensal or environmental bacteria. Food contamination by resistant bacteria might be a significant source of resistance genes for human bacteria but has never been precisely assessed, nor is it known whether organic products differ in this respect from conventionally produced products. We showed here, on a large year-long constructed sample set containing 399 products that, irrespective of their mode of production, raw fruits and vegetables are heavily contaminated by Gram-negative bacteria (GNB) resistant to multiple antibiotics. Most of these bacteria originate in the soil and environment. We focused on non-oxidative GNB resistant to third-generation cephalosporins, because of their potential impact on human health. Among them, species potentially pathogenic for immunocompetent hosts were rare. Of the products tested, 13% carried bacteria producing extended-spectrum beta-lactamases, all identified as Rahnella sp. which grouped into two phylotypes and all carrying the bla(RAHN) gene. Thus, both organic and conventional fruits and vegetables may constitute significant sources of resistant bacteria and of resistance genes.
Environmental Microbiology 11/2009; 12(3):608-15. · 5.84 Impact Factor
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ABSTRACT: Tigecycline is a glycylcycline antibiotic that inhibits protein synthesis including in isolates that are resistant to the tetracyclines by ribosomal protection or efflux. ...
Antimicrobial Agents and Chemotherapy 10/2009; 53(11):4953-4. · 4.84 Impact Factor
