scholarly journals Characterization of OXA-204, a Carbapenem-Hydrolyzing Class D β-Lactamase from Klebsiella pneumoniae

2012 ◽  
Vol 57 (1) ◽  
pp. 633-636 ◽  
Author(s):  
Anaïs Potron ◽  
Patrice Nordmann ◽  
Laurent Poirel

ABSTRACTAKlebsiella pneumoniaeclinical isolate recovered in Tunisia showed resistance to all β-lactams and decreased susceptibility to carbapenems.K. pneumoniae204 expressed the carbapenem-hydrolyzing β-lactamase OXA-204, differing from OXA-48 by two amino acid substitutions (Gln98His and Thr99Arg) (class D β-lactamase [DBL] numbering). OXA-48 and OXA-204 shared similar resistance profiles, hydrolyzing carbapenems but sparing broad-spectrum cephalosporins. TheblaOXA-204gene was located on a ca. 150-kb IncA/C-type plasmid, which also carried theblaCMY-4gene. TheblaOXA-204gene was associated with an ISEcp1element, whereas theblaOXA-48genes are usually associated with IS1999.

2011 ◽  
Vol 55 (10) ◽  
pp. 4896-4899 ◽  
Author(s):  
Anaïs Potron ◽  
Patrice Nordmann ◽  
Emilie Lafeuille ◽  
Zaina Al Maskari ◽  
Fatma Al Rashdi ◽  
...  

ABSTRACTKlebsiella pneumoniaeKP3 was isolated from a patient transferred from India to the Sultanate of Oman.K. pneumoniaeKP3 was resistant to all β-lactams, including carbapenems, and expressed the carbapenem-hydrolyzing β-lactamase OXA-181, which differs from OXA-48 by four amino acid substitutions. Compared to OXA-48, OXA-181 possessed a very similar hydrolytic profile. TheblaOXA-181gene was located on a 7.6-kb ColE-type plasmid and was linked to the insertion sequence ISEcp1. The ISEcp1-mediated one-ended transposition ofblaOXA-181was also demonstrated.


2016 ◽  
Vol 60 (5) ◽  
pp. 3199-3201 ◽  
Author(s):  
Aurélie Jayol ◽  
Patrice Nordmann ◽  
Marine Desroches ◽  
Jean-Winoc Decousser ◽  
Laurent Poirel

ABSTRACTAn extended-spectrum β-lactamase (ESBL)-producing and colistin-resistantKlebsiella pneumoniaeclinical isolate was recovered from a patient who was treated with cefotaxime. This isolate harbored ablaCTX-M-15ESBL gene that was associated with an ISEcp1insertion sequence. Transposition of that tandem occurred within the chromosomalmgrBgene, leading to inactivation of themgrBgene and consequently to acquired resistance to colistin. We showed here a coselection of colistin resistance as a result of a broad-spectrum cephalosporin selective pressure.


2020 ◽  
Vol 64 (8) ◽  
Author(s):  
Laurent Poirel ◽  
Xavier Vuillemin ◽  
Mario Juhas ◽  
Amandine Masseron ◽  
Ursina Bechtel-Grosch ◽  
...  

ABSTRACT KPC-50 is a KPC-3 variant identified from a Klebsiella pneumoniae clinical isolate recovered in Switzerland in 2019. Compared to KPC-3, KPC-50 shows (i) a three-amino-acid insertion (Glu-Ala-Val) between amino acids 276 and 277, (ii) an increased affinity to ceftazidime, (iii) a decreased sensitivity to avibactam, explaining the ceftazidime-avibactam resistance, and (iv) an association with a sharp reduction of its carbapenemase activity.


2016 ◽  
Vol 60 (6) ◽  
pp. 3709-3716 ◽  
Author(s):  
Yi-Hsiang Cheng ◽  
Tzu-Lung Lin ◽  
Yi-Tsung Lin ◽  
Jin-Town Wang

Colistin is a last-resort antibiotic for treatment of carbapenem-resistantKlebsiella pneumoniae. A recent study indicated that missense mutations in the CrrB protein contribute to colistin resistance. In our previous study, mechanisms of colistin resistance were defined in 17 of 26 colistin-resistantK. pneumoniaeclinical isolates. Of the remaining nine strains, eight were highly resistant to colistin. In the present study,crrABsequences were determined for these eight strains. Six separate amino acid substitutions in CrrB (Q10L, Y31H, W140R, N141I, P151S, and S195N) were detected. Site-directed mutagenesis was used to generatecrrBloci harboring individual missense mutations; introduction of the mutated genes into a susceptible strain, A4528, resulted in 64- to 1,024-fold increases in colistin MICs. ThesecrrBmutants showed increased accumulation ofH239_3062,H239_3059,pmrA,pmrC, andpmrHtranscripts by quantitative reverse transcription (qRT)-PCR. Deletion ofH239_3062(but not that ofH239_3059) in the A4528crrB(N141I) strain attenuated resistance to colistin, andH239_3062was accordingly namedcrrC. Similarly, accumulation ofpmrA,pmrC, andpmrHtranscripts induced bycrrB(N141I) was significantly attenuated upon deletion ofcrrC. Complementation ofcrrCrestored resistance to colistin and accumulation ofpmrA,pmrC, andpmrHtranscripts in acrrB(N141I) ΔcrrCstrain. In conclusion, novel individual CrrB amino acid substitutions (Y31H, W140R, N141I, P151S, and S195N) were shown to be responsible for colistin resistance. We hypothesize that CrrB mutations induce CrrC expression, thereby inducing elevated expression of thepmrHFIJKLMoperon andpmrC(an effect mediated via the PmrAB two-component system) and yielding increased colistin resistance.


2011 ◽  
Vol 55 (12) ◽  
pp. 5930-5932 ◽  
Author(s):  
Kyungwon Lee ◽  
Jong Hwa Yum ◽  
Dongeun Yong ◽  
Seok Hoon Jeong ◽  
Gian Maria Rossolini ◽  
...  

ABSTRACTThe TEM-107 extended-spectrum β-lactamase detected in aKlebsiella pneumoniaeclinical isolate had a Gly238Ser substitution compared to the TEM-43 β-lactamase. The MIC of ceftazidime was higher (64 μg/ml) than that of cefotaxime (2 μg/ml) for the isolate. Clavulanic acid reduced the MIC of ceftazidime 64-fold.


2000 ◽  
Vol 44 (2) ◽  
pp. 453-455 ◽  
Author(s):  
Catherine Neuwirth ◽  
Roger Labia ◽  
Eliane Siebor ◽  
Andre Pechinot ◽  
Stephanie Madec ◽  
...  

ABSTRACT TEM-56 produced by a Klebsiella pneumoniae clinical isolate is a novel β-lactamase of isoelectric point 6.4 that confers a moderate resistance level to expanded-spectrum cephalosporins. The amino acid sequence deduced from the corresponding bla gene showed two amino acid replacements with respect to the TEM-2 sequence: Glu-104 to Lys and His-153 to Arg. This enzyme showed catalytic properties close to those of TEM-18. Thus, TEM-56 appears as a new TEM mutant, an intermediary between TEM-18 and the extended-spectrum β-lactamase TEM-21.


2014 ◽  
Vol 58 (10) ◽  
pp. 6302-6305 ◽  
Author(s):  
Tatsuya Tada ◽  
Basudha Shrestha ◽  
Tohru Miyoshi-Akiyama ◽  
Kayo Shimada ◽  
Hiroshi Ohara ◽  
...  

ABSTRACTA novel New Delhi metallo-β-lactamase variant, NDM-12, was identified in a carbapenem-resistantEscherichia coliclinical isolate obtained from a urine sample from a patient in Nepal. NDM-12 differed from NDM-1 by two amino acid substitutions (M154L and G222D). The enzymatic activities of NDM-12 against β-lactams were similar to those of NDM-1, although NDM-12 showed lowerkcat/Kmratios for all β-lactams tested except doripenem. TheblaNDM-12gene was located in a plasmid of 160 kb.


2013 ◽  
Vol 57 (7) ◽  
pp. 3072-3077 ◽  
Author(s):  
I. Lysnyansky ◽  
I. Gerchman ◽  
I. Mikula ◽  
F. Gobbo ◽  
S. Catania ◽  
...  

ABSTRACTThein vitroactivity of enrofloxacin against 73Mycoplasma synoviaefield strains isolated in Israel and Europe was determined by broth microdilution. Decreased susceptibility to enrofloxacin was identified in 59% of strains, with the MICs ranging from 1 to >16 μg/ml. The estimated MIC50and MIC90values for enrofloxacin were 2 and 8 μg/ml, respectively. Moreover, this study showed that 92% of recent Israeli field isolates (2009 to 2011) ofM. synoviaehave MICs of ≥2 μg/ml to enrofloxacin. Comparison of the quinolone resistance-determining regions (QRDRs) inM. synoviaeisolates revealed a clear correlation between the presence of one of the amino acid substitutions Asp79-Asn, Thr80-Ala/Ile, Ser81-Pro, and Asp84-Asn/Tyr/His of the ParC QRDR and decreased susceptibility to enrofloxacin (MIC, ≥1 μg/ml). Amino acid substitutions at positions GyrA 87, GyrB 401/402, and ParE 420/454 were also identified, but there was no clear-cut correlation with susceptibility to enrofloxacin. Comparison ofvlhAmolecular profiles revealed the presence of 9 different genotypes in the IsraeliM. synoviaefield isolates and 10 genotypes in the European isolates; only onevlhAgenotype (type 4) was identified in both cohorts. Based on results ofvlhAmolecular typing, several mechanisms for emergence and dissemination of Israeli enrofloxacin-resistantM. synoviaeisolates are suggested.


2017 ◽  
Vol 61 (5) ◽  
Author(s):  
Katarina Novović ◽  
Anika Trudić ◽  
Snežana Brkić ◽  
Zorica Vasiljević ◽  
Milan Kojić ◽  
...  

ABSTRACT Twenty-seven colistin-resistant, carbapenemase-producing Klebsiella pneumoniae isolates were identified from hospitals in Serbia. All isolates were bla CTX-M-15 positive; ST101, ST888, ST437, ST336, and ST307 were bla OXA-48 positive; and ST340 was bla NDM-1 positive. ST307 had an insertion, and ST336 had a premature stop codon in the mgrB gene. Amino acid substitutions were detected in PmrAB of isolates ST101, ST888, ST336, and ST307. The mcr-1 and mcr-2 were not detected. An increase in phoP, phoQ, and pmrK gene transcription was detected for all sequence types.


2020 ◽  
Vol 65 (1) ◽  
pp. e01429-20
Author(s):  
Vincenzo Di Pilato ◽  
Noemi Aiezza ◽  
Valentina Viaggi ◽  
Alberto Antonelli ◽  
Luigi Principe ◽  
...  

ABSTRACTThis study reports on the characterization of a Klebsiella pneumoniae clinical isolate showing high-level resistance to ceftazidime-avibactam associated with the production of KPC-53, a KPC-3 variant exhibiting a Leu167Glu168 duplication in the Ω-loop and a loss of carbapenemase activity. Whole-genome sequencing (WGS) revealed the presence of two copies of blaKPC-53, located on a pKpQIL-like plasmid and on a plasmid prophage of the Siphoviridae family, respectively. The present findings provide new insights into the mechanisms of resistance to ceftazidime-avibactam.


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