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Plasmid pKpQIL encoding KPC-3 and TEM-1 confers carbapenem resistance in an extremely drug-resistant epidemic Klebsiella pneumoniae strain.
J Antimicrob Chemother. 2010 Feb; 65(2):243-8.JA

Abstract

OBJECTIVES

An extremely drug-resistant (XDR) clone of KPC-3-producing Klebsiella pneumoniae emerged in Israel in 2006, causing a nationwide outbreak. We aimed to characterize the local KPC-3-encoding plasmid carried by these isolates and study its contribution to antibiotic resistance.

METHODS

Mechanisms of carbapenem resistance were investigated in seven selected isolates (isolated between 2006 and 2008) belonging to the epidemic clone. Isolates underwent MIC testing, and were examined for the presence of KPC, Tn4401, class I integron elements and additional antibiotic resistance genes. Plasmids were analysed by transformation, transconjugation, restriction mapping, curing and complementation experiments. Outer membrane protein (OMP) analysis was performed.

RESULTS

OMP analysis did not reveal loss of porins. KPC-3-producing K. pneumoniae isolates possessed various plasmids but all harboured a common self-transmissible 105 kb plasmid, termed pKpQIL, encoding bla(TEM-1) and bla(KPC-3). Curing of pKpQIL led to a complete loss of resistance to cephalosporins and carbapenems, proving its crucial role in carbapenem resistance. Transformation of plasmid pKpQIL into the cured Klebsiella strain resulted in full reconstitution of carbapenem resistance. The presence of all Tn4401 transposon elements located upstream of the KPC-3 gene was detected by PCR and sequencing. pKpQIL lacked additional antibiotic resistance genes.

CONCLUSIONS

Our findings demonstrate the presence of pKpQIL, a 105 kb KPC-3- and TEM-1-encoding plasmid, in the XDR K. pneumoniae epidemic strain in Israel. pKpQIL is unique and appears consistently in all isolates of this clone over the years. The extensive beta-lactam resistance phenotype of this clone is primarily mediated by this single self-transmissible plasmid.

Authors+Show Affiliations

Molecular Epidemiology and Antimicrobial Resistance Laboratory, Division of Epidemiology, Tel Aviv Medical Center, Tel Aviv, Israel.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19939824

Citation

Leavitt, Azita, et al. "Plasmid pKpQIL Encoding KPC-3 and TEM-1 Confers Carbapenem Resistance in an Extremely Drug-resistant Epidemic Klebsiella Pneumoniae Strain." The Journal of Antimicrobial Chemotherapy, vol. 65, no. 2, 2010, pp. 243-8.
Leavitt A, Chmelnitsky I, Ofek I, et al. Plasmid pKpQIL encoding KPC-3 and TEM-1 confers carbapenem resistance in an extremely drug-resistant epidemic Klebsiella pneumoniae strain. J Antimicrob Chemother. 2010;65(2):243-8.
Leavitt, A., Chmelnitsky, I., Ofek, I., Carmeli, Y., & Navon-Venezia, S. (2010). Plasmid pKpQIL encoding KPC-3 and TEM-1 confers carbapenem resistance in an extremely drug-resistant epidemic Klebsiella pneumoniae strain. The Journal of Antimicrobial Chemotherapy, 65(2), 243-8. https://doi.org/10.1093/jac/dkp417
Leavitt A, et al. Plasmid pKpQIL Encoding KPC-3 and TEM-1 Confers Carbapenem Resistance in an Extremely Drug-resistant Epidemic Klebsiella Pneumoniae Strain. J Antimicrob Chemother. 2010;65(2):243-8. PubMed PMID: 19939824.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Plasmid pKpQIL encoding KPC-3 and TEM-1 confers carbapenem resistance in an extremely drug-resistant epidemic Klebsiella pneumoniae strain. AU - Leavitt,Azita, AU - Chmelnitsky,Inna, AU - Ofek,Itzhak, AU - Carmeli,Yehuda, AU - Navon-Venezia,Shiri, Y1 - 2009/11/24/ PY - 2009/11/27/entrez PY - 2009/11/27/pubmed PY - 2010/3/18/medline SP - 243 EP - 8 JF - The Journal of antimicrobial chemotherapy JO - J Antimicrob Chemother VL - 65 IS - 2 N2 - OBJECTIVES: An extremely drug-resistant (XDR) clone of KPC-3-producing Klebsiella pneumoniae emerged in Israel in 2006, causing a nationwide outbreak. We aimed to characterize the local KPC-3-encoding plasmid carried by these isolates and study its contribution to antibiotic resistance. METHODS: Mechanisms of carbapenem resistance were investigated in seven selected isolates (isolated between 2006 and 2008) belonging to the epidemic clone. Isolates underwent MIC testing, and were examined for the presence of KPC, Tn4401, class I integron elements and additional antibiotic resistance genes. Plasmids were analysed by transformation, transconjugation, restriction mapping, curing and complementation experiments. Outer membrane protein (OMP) analysis was performed. RESULTS: OMP analysis did not reveal loss of porins. KPC-3-producing K. pneumoniae isolates possessed various plasmids but all harboured a common self-transmissible 105 kb plasmid, termed pKpQIL, encoding bla(TEM-1) and bla(KPC-3). Curing of pKpQIL led to a complete loss of resistance to cephalosporins and carbapenems, proving its crucial role in carbapenem resistance. Transformation of plasmid pKpQIL into the cured Klebsiella strain resulted in full reconstitution of carbapenem resistance. The presence of all Tn4401 transposon elements located upstream of the KPC-3 gene was detected by PCR and sequencing. pKpQIL lacked additional antibiotic resistance genes. CONCLUSIONS: Our findings demonstrate the presence of pKpQIL, a 105 kb KPC-3- and TEM-1-encoding plasmid, in the XDR K. pneumoniae epidemic strain in Israel. pKpQIL is unique and appears consistently in all isolates of this clone over the years. The extensive beta-lactam resistance phenotype of this clone is primarily mediated by this single self-transmissible plasmid. SN - 1460-2091 UR - https://www.unboundmedicine.com/medline/citation/19939824/Plasmid_pKpQIL_encoding_KPC_3_and_TEM_1_confers_carbapenem_resistance_in_an_extremely_drug_resistant_epidemic_Klebsiella_pneumoniae_strain_ L2 - https://academic.oup.com/jac/article-lookup/doi/10.1093/jac/dkp417 DB - PRIME DP - Unbound Medicine ER -