2022
DOI: 10.1128/msystems.00476-22
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Systematic Analysis of Mobile Genetic Elements Mediating β-Lactamase Gene Amplification in Noncarbapenemase-Producing Carbapenem-Resistant Enterobacterales Bloodstream Infections

Abstract: Carbapenem-resistant Enterobacterales (CRE) are considered urgent antimicrobial resistance (AMR) threats. The vast majority of CRE research has focused on carbapenemase-producing Enterobacterales (CPE) even though noncarbapenemase-producing CRE (non-CP-CRE) comprise 50% or more of isolates in some surveillance studies.

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Cited by 23 publications
(60 citation statements)
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References 73 publications
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“…This allowed us to find that carbapenem-susceptible ESC-R-Ec strains have lower blaCTX-M copy numbers relative to carbapenem-resistant ESC-R-Ec strains consistent with an important role of blaCTX-M amplification in the transition from ESC-R to the non-CP-CRE phenotype. Moreover, via an analysis of paired isolates from the same patients, we found significant blaCTX-M amplifications suggesting that such amplifications are likely an adaptive mechanism to antimicrobial exposure in the host as has been observed by our group and others in the laboratory environment (31,32,42). Together with recently published data from ESBL-positive E. coli strains isolated in St.…”
Section: Esc-r-ec Populationsupporting
confidence: 83%
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“…This allowed us to find that carbapenem-susceptible ESC-R-Ec strains have lower blaCTX-M copy numbers relative to carbapenem-resistant ESC-R-Ec strains consistent with an important role of blaCTX-M amplification in the transition from ESC-R to the non-CP-CRE phenotype. Moreover, via an analysis of paired isolates from the same patients, we found significant blaCTX-M amplifications suggesting that such amplifications are likely an adaptive mechanism to antimicrobial exposure in the host as has been observed by our group and others in the laboratory environment (31,32,42). Together with recently published data from ESBL-positive E. coli strains isolated in St.…”
Section: Esc-r-ec Populationsupporting
confidence: 83%
“…There were 297 ESC-R isolates that had paired-end 150 base pair reads that passed quality control assessed using fastqc-v0.11.9. We performed long-read sequencing on an nine isolates using the Oxford Nanopore Technologies GridION platform as described previously (32).…”
Section: Genomic Sequencingmentioning
confidence: 99%
“…We determined that all three isolates belonged to ST410 based on in silico typing using WGS data. For the purpose of determining genetic relatedness of these serial isolates in the context of ST410 we have previously sequenced, 21, 22 we created a maximum likelihood phylogenetic tree inferred from a recombination free, core genome alignment of 15 ST410 isolates collected from 10 patients ( Figure 2 ). After accounting for recombination regions, there were 831 polymorphic sites with a median pairwise SNP distance of 210 (interquartile range = 52.5).…”
Section: Resultsmentioning
confidence: 99%
“…ST410 isolate WGS data from previous studies can be acquired in BioProject PRJNA836696 and BioProject PRJNA388450. 21, 22…”
Section: Methodsmentioning
confidence: 99%
“…57 Noteworthy, CRE with high efflux activity or permeability defects may express any of these mechanisms paired to production of other β-lactamases such as AmpC cephalosporinases or extended-spectrum β-lactamases (ESBLs), indicating the heterogeneity of mechanisms driving the development of carbapenem resistance. 85 In pneumonia, antibiotic resistance profiles of Enterobacterales have gradually changed, indicating that close monitoring of those pathogens is fundamental for preventing further rise of resistance, development of treatment guidelines, and improving clinical therapy. For example, in China, an analysis of CRE in HAP over one decade showed an increase in the prevalence of these organisms from 0.8% to 11.6%.…”
Section: Carbapenem-resistant Enterobacterales (Cre)mentioning
confidence: 99%