Transferable plasmid mediating resistance to multiple antimicrobial agents in Klebsiella pneumoniae isolates in Greece

Galani, Irene; Xirouchaki, E.; Kanellakopoulou, K.; Petrikkos, George; Giamarellou, Helen

doi:10.1046/j.1469-0691.2002.00391.x

Cited by 21 publications

(14 citation statements)

References 35 publications

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“…The REP-PCR, ERIC-PCR, and RAPD fingerprinting techniques have previously been used for typing K. pneumoniae strains (4,5,7,8,9,13,16,30). However, these studies were performed with a small number of strains, and it was prob- Therefore, although the lack of reproducibility of the RAPD method has been demonstrated several times, the power of discrimination and reproducibility of the ERIC-PCR, REP-PCR, and RAPD techniques remain unknown.…”

Section: Discussionmentioning

confidence: 99%

“…Resistance of this species to expanded-spectrum cephalosporins was first described in the early 1980s, and an increase in resistance has occurred since 1986 (3,7,8,18,22). Resistant isolates probably acquire their resistance by producing extended-spectrum ␤-lactamases (ESBLs) (22).…”

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confidence: 99%

“…Moreover, repetitive extragenic palindromic sequencebased PCR (REP-PCR) and enterobacterial repetitive intergenic consensus sequence PCR (ERIC-PCR) have also been successfully used for typing K. pneumoniae isolates (4,7,8,13,16). However, the comparative typing ability, reproducibility, discriminatory power, and efficiency of these methods were not fully investigated in all of these studies.…”

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confidence: 99%

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Risk Factors for Colonization and Infection in a Hospital Outbreak Caused by a Strain of Klebsiella pneumoniae with Reduced Susceptibility to Expanded-Spectrum Cephalosporins

Cartelle¹,

Tomás²,

Pértega

et al. 2004

J Clin Microbiol

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, an increase in the number of Klebsiella pneumoniae isolates with reduced susceptibility to expanded-spectrum cephalosporins (RSKp) was detected in the neonatal unit of the Juan Canalejo Hospital, and 21 patients were either colonized or infected by the bacterial isolates. The current "gold standard" method for typing K. pneumoniae isolates is pulsed-field gel electrophoresis. However, this technique is expensive and time-consuming. In a search for faster and accurate alternatives to this method, we investigated PCR-based fingerprinting techniques (

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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Risk Factors for Colonization and Infection in a Hospital Outbreak Caused by a Strain of Klebsiella pneumoniae with Reduced Susceptibility to Expanded-Spectrum Cephalosporins

Cartelle¹,

Tomás²,

Pértega

et al. 2004

J Clin Microbiol

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“…The semisynthetic aminoglycoside amikacin (AMK) has been very useful in the treatment of multiresistant infections because a limited number of modifying enzymes, such as AAC(6Ј)-I-type acetyltransferases, are able to inactivate it (37). However, the spread of these enzymes has rendered AMK all but useless in some regions of the world (6,30,38,45). Development of strategies to inhibit the expression of resistance genes could preserve the efficacy of AMK.…”

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confidence: 99%

External Guide Sequences Targeting the aac(6′)-Ib mRNA Induce Inhibition of Amikacin Resistance

Soler-Bistué

Sarno

et al. 2007

Antimicrob Agents Chemother

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The dissemination of AAC(6)-I-type acetyltransferases have rendered amikacin and other aminoglycosides all but useless in some parts of the world. Antisense technologies could be an alternative to extend the life of these antibiotics. External guide sequences are short antisense oligoribonucleotides that induce RNase Pmediated cleavage of a target RNA by forming a precursor tRNA-like complex. Thirteen-nucleotide external guide sequences complementary to locations within five regions accessible for interaction with antisense oligonucleotides in the mRNA that encodes AAC(6)-Ib were analyzed. While small variations in the location targeted by different external guide sequences resulted in big changes in efficiency of binding to native aac(6)-Ib mRNA, most of them induced high levels of RNase P-mediated cleavage in vitro. Recombinant plasmids coding for selected external guide sequences were introduced into Escherichia coli harboring aac(6)-Ib, and the transformant strains were tested to determine their resistance to amikacin. The two external guide sequences that showed the strongest binding efficiency to the mRNA in vitro, EGSC3 and EGSA2, interfered with expression of the resistance phenotype at different degrees. Growth curve experiments showed that E. coli cells harboring a plasmid coding for EGSC3, the external guide sequence with the highest mRNA binding affinity in vitro, did not grow for at least 300 min in the presence of 15 g of amikacin/ml. EGSA2, which had a lower mRNA-binding affinity in vitro than EGSC3, inhibited the expression of amikacin resistance at a lesser level; growth of E. coli harboring a plasmid coding for EGSA2, in the presence of 15 g of amikacin/ml was undetectable for 200 min but reached an optical density at 600 nm of 0.5 after 5 h of incubation. Our results indicate that the use of external guide sequences could be a viable strategy to preserve the efficacy of amikacin.Aminoglycoside antibiotics act by interfering with the decoding process (12,22,25,39) and are used to treat infections caused by aerobic gram-negative or gram-positive bacteria. In this latter case they are used in combination with other antibiotics (46). However, the rise in resistant and multiresistant strains, usually harboring aminoglycoside modifying enzymes, has limited the successful use of aminoglycosides in the treatment of serious infections (17, 37). The semisynthetic aminoglycoside amikacin (AMK) has been very useful in the treatment of multiresistant infections because a limited number of modifying enzymes, such as AAC(6Ј)-I-type acetyltransferases, are able to inactivate it (37). However, the spread of these enzymes has rendered AMK all but useless in some regions of the world (6,30,38,45). Development of strategies to inhibit the expression of resistance genes could preserve the efficacy of AMK. Antisense oligonucleotide technologies may be an alternative for this purpose. A variety of antisense strategies have been applied before to inhibit gene expression in prokaryotic systems (4,10,23,28,34,44).RNase...

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“…The aminoglycoside amikacin (AMK) has been very useful in the treatment of infections caused by multiresistant bacteria because it is refractory to the actions of most modifying enzymes (19,33,37). However, the spread of AAC(6Ј)-I-type acetyltransferases, enzymes capable of catalyzing the inactivation of AMK, has rendered this antibiotic all but useless in some parts of the world (1,10,11,44). Although research is being conducted to generate new aminoglycoside antibiotics (15), AMK and netilmicin remain the only semisynthetic aminoglycosides available.…”

mentioning

confidence: 99%

Inhibition of Aminoglycoside 6′- N -Acetyltransferase Type Ib-Mediated Amikacin Resistance by Antisense Oligodeoxynucleotides

Sarno

Weinsetel

et al. 2003

Antimicrob Agents Chemother

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Amikacin has been very useful in the treatment of infections caused by multiresistant bacteria because it is refractory to the actions of most modifying enzymes. However, the spread of AAC(6)-I-type acetyltransferases, enzymes capable of catalyzing inactivation of amikacin, has rendered this antibiotic all but useless in some parts of the world. The aminoglycoside 6-N-acetyltransferase type Ib, which is coded for by the aac(6)-Ib gene, mediates resistance to amikacin and other aminoglycosides. RNase H mapping and computer prediction of the secondary structure led to the identification of five regions accessible for interaction with antisense oligodeoxynucleotides in the aac(6)-Ib mRNA. Oligodeoxynucleotides targeting these regions could bind to native mRNA with different efficiencies and mediated RNase H digestion. Selected oligodeoxynucleotides inhibited AAC(6)-Ib synthesis in cell-free coupled transcription-translation assays. After their introduction into an Escherichia coli strain harboring aac(6)-Ib by electroporation, some of these oligodeoxynucleotides decreased the level of resistance to amikacin. Our results indicate that use of antisense compounds could be a viable strategy to preserve the efficacies of existing antibiotics to which bacteria are becoming increasingly resistant.

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Transferable plasmid mediating resistance to multiple antimicrobial agents in Klebsiella pneumoniae isolates in Greece

Cited by 21 publications

References 35 publications

Risk Factors for Colonization and Infection in a Hospital Outbreak Caused by a Strain of Klebsiella pneumoniae with Reduced Susceptibility to Expanded-Spectrum Cephalosporins

Risk Factors for Colonization and Infection in a Hospital Outbreak Caused by a Strain of Klebsiella pneumoniae with Reduced Susceptibility to Expanded-Spectrum Cephalosporins

External Guide Sequences Targeting the aac(6′)-Ib mRNA Induce Inhibition of Amikacin Resistance

Inhibition of Aminoglycoside 6′- N -Acetyltransferase Type Ib-Mediated Amikacin Resistance by Antisense Oligodeoxynucleotides

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