A novel ceftazidime-hydrolysing extended-spectrum  -lactamase, CTX-M-54, with a single amino acid substitution at position 167 in the omega loop

Bae, Il Kwon; Lee, Byung Ho; Hwang, Hyunyong; Jeong, Seok Hoon; Hong, Seong Geun; Chang, Chulhun L.; Kwak, Hyo‐Sun; Kim, Hyoung Jin; Youn, Hasik

doi:10.1093/jac/dkl252

Cited by 38 publications

(32 citation statements)

References 13 publications

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“…The already-described P167S/T and D240G mutations involved in ceftazidime resistance phenotypes in natural isolates (2,6,30,36) were consistently found in our in vitro evolution experiments under ceftazidime selective pressure, as observed previously (14,22,37).…”

Section: Discussionsupporting

confidence: 88%

Mutational Events in Cefotaximase Extended-Spectrum β-Lactamases of the CTX-M-1 Cluster Involved in Ceftazidime Resistance

Novais

Cantón

Coque

et al. 2008

Antimicrob Agents Chemother

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CTX-M ␤-lactamases, which show a high cefotaxime hydrolytic activity, constitute the most prevalent extended-spectrum ␤-lactamase (ESBL) type found among clinical isolates. The recent explosive diversification of CTX-M enzymes seems to have taken place due to the appearance of more efficient enzymes which are capable of hydrolyzing both cefotaxime and ceftazidime, especially among the CTX-M-1 cluster. A combined strategy of in vitro stepwise evolution experiments using bla CTX-M-1 , bla CTX-M-3 , and bla CTX-M-10 genes and site-directed mutagenesis has been used to evaluate the role of ceftazidime and other ␤-lactam antibiotics in triggering the diversity found among enzymes belonging to this cluster. Two types of mutants, P167S and D240G, displaying high ceftazidime MICs but reduced resistance to cefotaxime and/or cefepime, respectively, were identified. Such an antagonistic pleiotropic effect was particularly evident with P167S/T mutations. The incompatibility between P167S and D240G changes was demonstrated, since double mutants reduced susceptibility to both ceftazidime and cefotaxime-cefepime; this may explain the absence of strains containing both mutations in the clinical environment. The role of A77V and N106S mutations, which are frequently associated with P167S/T and/or D240G, respectively, in natural strains, was investigated. The presence of A77V and N106S contributes to restore a high-level cefotaxime resistance phenotype, but only when associated with mutations P167S and D240G, respectively. However, A77V mutation increases resistance to both cefotaxime and ceftazidime when associated with CTX-M-10. This suggests that in this context this mutation might be considered a primary site involved in resistance to broad-spectrum cephalosporins.␤-Lactam agents constitute not only the most widely and frequently used group of antibacterial drugs but also the one that includes the largest variety of molecules. Continuous exposure to a diverse array of ␤-lactams seems to have been driving the explosive diversification found among all ␤-lactamase groups (18,29). A number of investigations have identified the amino acid positions among classic TEM, SHV, or OXA enzymes that evolved under these multiple and coincidental selective events. Such changes are responsible for increasing affinity and hydrolytic activity against the newest ␤-lactams, leading to extended-spectrum ␤-lactamases (ESBLs) (11,21,34).CTX-M enzymes probably originated in environmental organisms, where they confer a negligible level of resistance to cefotaxime (12, 27, 32). However, when present as acquired ␤-lactamases in Enterobacteriaceae (known as cefotaximases) they confer a high cefotaxime-hydrolytic activity (4, 19). Since the original description in 1989 (4), a rapid and extensive radiation of different CTX-M clusters and variants has occurred, with more than 60 molecular forms described to date and classified into five clusters based on amino acid sequence homology (http://www.lahey.org /studies/webt.htm). Such accelerated variability mig...

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Section: Discussionsupporting

confidence: 88%

Mutational Events in Cefotaximase Extended-Spectrum β-Lactamases of the CTX-M-1 Cluster Involved in Ceftazidime Resistance

Novais

Cantón

Coque

et al. 2008

Antimicrob Agents Chemother

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“…The CTX-M-15 type enzyme differs from that of CTX-M-3 type by an asparagine to glycine substitution at codon 240, which leads to increased activity against ceftazidime. These CTX-M-15 type enzymes may have been selected by the increasing use of ceftazidime in clinical practice [19][20][21].…”

Section: Discussionmentioning

confidence: 99%

The characterization of ESBL genes in Escherichia coli and Klebsiella pneumoniae causing nosocomial infections in Vietnam

Trang

Nga

Hiep

et al. 2013

J Infect Dev Ctries

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Background: Extended-spectrum β-lactamases (ESBLs) are enzymes capable of hydrolyzing oxyimino-β-lactams and inducing resistance to third generation cephalosporins. The genes encoding ESBLs are widespread and generally located on highly transmissible resistance plasmids. We aimed to investigate the complement of ESBL genes in E. coli and Klebsiella pneumoniae causing nosocomial infections in hospitals in Ho Chi Minh City, Vietnam. Methodology: Thirty-two non-duplicate isolates of E. coli and Klebsiella pneumoniae causing nosocomial infections, isolated between March and June 2010, were subjected to antimicrobial susceptibility testing. All isolates were PCR-amplified to detect the bla SHV , bla TEM and bla CTX-M ESBL genes and subjected to plasmid analysis. Results: We found that co-resistance to multiple antimicrobials was highly prevalent, and we report the predominance of the bla CTX-M-15 and bla CTX-M-27 genes, located on highly transmissible plasmids ranging from 50 to 170 kb in size. Conclusions: Our study represents a snap shot of ESBL-producing enteric bacteria causing nosocomial infections in this setting. We suggest that antimicrobial resistance in nosocomial E. coli and Klebsiella pneumoniae is rampant in Vietnam and ESBL organisms are widespread. In view of these data and the dramatic levels of antimicrobial resistance reported in Vietnam we advocate an urgent review of antimicrobial use in the Vietnamese healthcare system.

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“…All the Salmonella isolates were examined for the presence of bla CTX-M by PCR and direct sequencing using 4 primer sets (Table 1) (18,19). The PCR reaction was performed under the following conditions: 949 C for 5 min, followed by 35 cycles of 949 C for 30 s, 609 C for 30 s, and 729 C for 30 s, with a final extension at 729 C for 5 min.…”

Section: Methodsmentioning

confidence: 99%

Serotyping and Antimicrobial Susceptibility of <i>Salmonella</i> spp.: Nationwide Multicenter Study in Korea

et al. 2013

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SUMMARY:The study aimed to investigate the prevalence of various serotypes and extended-spectrum b-lactamase-producing features of Salmonella strains and to determine the antimicrobial susceptibility of 256 Salmonella strains other than Salmonella serotype Typhi, which were isolated at 12 university hospitals in Korea. We identified 46 serotypes of Salmonella spp. Serogroup D was the most common (39.5z), followed by B (32.4z), C (22.7z), E (2.7z), A (2.3z), and G (0.4z). The three most common Salmonella serotypes were Enteritidis (36.3z), Typhimurium (16.8z), and Infantis (7.8z). Six strains that belonged to serotype Paratyphi A and nine that belonged to serotype Paratyphi B were also detected. The 256 Salmonella strains had a 38.7z rate of resistance to ampicillin, 23.0z to chloramphenicol, 8.2z to cefotaxime, 8.6z to ceftriaxone, and 6.3z to trimethoprim-sulfamethoxazole. The antimicrobial resistance rates of Salmonella serogroups B and D were higher than those of the other serogroups. Seven isolates carried bla CTX-M : four CTX-M-15, two CTX-M-14, and one CTX-M-3.

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A novel ceftazidime-hydrolysing extended-spectrum -lactamase, CTX-M-54, with a single amino acid substitution at position 167 in the omega loop

Cited by 38 publications

References 13 publications

Mutational Events in Cefotaximase Extended-Spectrum β-Lactamases of the CTX-M-1 Cluster Involved in Ceftazidime Resistance

Mutational Events in Cefotaximase Extended-Spectrum β-Lactamases of the CTX-M-1 Cluster Involved in Ceftazidime Resistance

The characterization of ESBL genes in Escherichia coli and Klebsiella pneumoniae causing nosocomial infections in Vietnam

Serotyping and Antimicrobial Susceptibility of <i>Salmonella</i> spp.: Nationwide Multicenter Study in Korea

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