Global epidemiology of CTX-M-type β-lactam resistance in human and animal

Rana, Chanchal; Rajput, Shiveeli; Behera, Manisha; Gautam, Devika; Vazhayil, Vikas; Vats, Ashutosh; Roshan, Mayank; Ghorai, Soma Mondal; De, Sachinandan

doi:10.1016/j.cimid.2022.101815

Cited by 12 publications

(5 citation statements)

References 35 publications

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“…Among these, the most common were groups bla CTX-M-1 and bla CTX-M-9 , in which bla CTX-M-14 and bla CTX-M-15 were the most common subtypes in recent years. 41 In this study, we detected a variety of drug resistance genes, and the most common was bla CTX-M , which was mainly distributed in five subtypes. These included bla CTX-M-27 (n = 16), bla CTX-M-14 (n = 15), bla CTX-M-15 (n = 11), bla CTX-M-55 (n = 14) and bla CTX-M-65 (n = 5).…”

Section: Discussionmentioning

confidence: 91%

The Characteristics of Extended-Spectrum β-Lactamases (ESBLs)-Producing Escherichia coli in Bloodstream Infection

Li¹,

Xu²,

Tang³

et al. 2023

IDR

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Background Bloodstream infection (BSI) is a common type of infection frequently diagnosed in clinics. The emergence and spread of ESBLs-producing Escherichia coli ( E. coli ) has emerged as one of the biggest challenges in global community health. Methods The production of ESBLs was determined by the composite disk diffusion method. The expression of the various resistance and virulence genes were detected by PCR and sequencing. Multi-locus sequence typing (MLST) and phylogenetic groups were used for the classification. The transfer of resistant plasmids was determined by conjugation assay. The statistical differences were analyzed using Statistical Product and Service Solutions (SPSS) version 23.0. Results A total of 60 strains of ESBLs-producing E. coli were collected. The resistance genes that were identified included bla CTX-M , bla TEM , bla SHV , bla OXA-1 and mcr-1 . The most common one was the bla CTX-M including bla CTX-M-27 (n = 16), bla CTX-M-14 (n = 15), bla CTX-M-15 (n = 11), bla CTX-M-55 (n = 14) and bla CTX-M-65 (n = 5). A total of 31 STs were detected, and the most abundant among which was ST131 (n = 16, 26.7%). Most of the E. coli (n = 46, 76.7%) belonged to the groups B2 and D. And some virulence genes were related to the classification of the E. coli . Among them, the detection rates of hek/hra, kpsMII and papGII-III in groups B2 and D were higher than those in groups A and B1. The detection rates of cnf1, iucC and papGII-III in ST131 were higher than those in non-ST131. And the distributions of hek/hra, iroN, iucC, kpsMII and papGII-III were related to the bla CTX-M subtypes. Finally, most bacterial (n = 32, 53.3%) resistance genes could be transferred between the bacteria by plasmids, especially IncFIB. Conclusion ESBLs-producing E. coli in BSI exhibited had high resistance rates and carried a variety of virulence factors (VFs). This is necessary to strengthen the monitoring of ESBLs-producing isolates in the medical environment.

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Section: Discussionmentioning

confidence: 91%

The Characteristics of Extended-Spectrum β-Lactamases (ESBLs)-Producing Escherichia coli in Bloodstream Infection

Li¹,

Xu²,

Tang³

et al. 2023

IDR

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“…Re-sensitization activity was observed in the programmed CRISPR-Cas9 with the highest efficacy, the second candidate target sequence of bla CTX-M group 1 and that of bla CTX-M group 9 can be found in up to 99% (107 of 108 variants) and 97% (69 of 71 variants) of the bla CTX-M variants in each group, respectively [ 6 ]. In vitro efficacy was examined for the prevalent variants that were available for plasmid construction, and further variants should be further evaluated.…”

Section: Discussionmentioning

confidence: 99%

“…bla CTX-M , which encodes cefotaximase-Munich (CTX-M) enzyme originated from Kluyvera spp., is the most abundantly distributed ESBL-encoding gene in Enterobacterales and is one of the β-lactamase family that comprises numerous variants [ 4 ]. To date, 242 variants of CTX-M have been identified and are classified into four groups based on >94% amino acid sequence identity, including CTX-M groups 1, 2, 9, and 8/25 [ 5 , 6 ]. bla CTX-M-15 in group 1 and bla CTX-M-14 in group 9 are the most prevalent variants of concern worldwide, including South-East Asia [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Non-replicative phage particles delivering CRISPR-Cas9 to target major blaCTX-M variants

Nittayasut,

Yata,

Chirakul

et al. 2024

PLoS ONE

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Cluster regularly interspaced short palindromic repeats and CRISPR associated protein 9 (CRISPR-Cas9) is a promising tool for antimicrobial re-sensitization by inactivating antimicrobial resistance (AMR) genes of bacteria. Here, we programmed CRISPR-Cas9 with common spacers to target predominant blaCTX-M variants in group 1 and group 9 and their promoter in an Escherichia coli model. The CRISPR-Cas9 was delivered by non-replicative phagemid particles from a two-step process, including insertion of spacer in CRISPR and construction of phagemid vector. Spacers targeting blaCTX-M promoters and internal sequences of blaCTX-M group 1 (blaCTX-M-15 and -55) and group 9 (blaCTX-M-14, -27, -65, and -90) were cloned into pCRISPR and phagemid pRC319 for spacer evaluation and phagemid particle production. Re-sensitization and plasmid clearance were mediated by the spacers targeting internal sequences of each group, resulting in 3 log10 to 4 log10 reduction of the ratio of resistant cells, but not by those targeting the promoters. The CRISPR-Cas9 delivered by modified ΦRC319 particles were capable of re-sensitizing E. coli K-12 carrying either blaCTX-M group 1 or group 9 in a dose-dependent manner from 0.1 to 100 multiplicity of infection (MOI). In conclusion, CRISPR-Cas9 system programmed with well-designed spacers targeting multiple variants of AMR gene along with a phage-based delivery system could eliminate the widespread blaCTX-M genes for efficacy restoration of available third-generation cephalosporins by reversal of resistance in bacteria.

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“…To further evaluate the potential of our platform in different clinical isolates and with a different antibiotic, we investigated the cefotaxime re-sensitization in two E. coli strains expressing the blactx-M-14 and blactx-M-15 genes. CTX-M enzymes represent a group of extended-spectrum β-lactamases (ESBLs) disseminated worldwide, with CTX-M-14 and CTX-M-15 being the most prevalent variants in gram-negative pathogens 51,52 . The two clinical isolates are part of the Natural Isolates with Low Subcultures (NILS) pathogenic E. coli collection 46 , and were collected from blood (blactx-M-14 strain) and urine (blactx-M-15 strain) samples.…”

Section: Horizontal Transfer Of Crispri Repression Devices In Clinica...mentioning

confidence: 99%

Harnessing CRISPR interference to re-sensitize laboratory strains and clinical isolates to last resort antibiotics

Chiacchiera,

Casanova,

Bellato

et al. 2024

Preprint

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The global race against antimicrobial resistance requires novel antimicrobials that are not only effective in killing specific bacteria, but also minimize the emergence of new resistances. Recently, CRISPR/Cas-based antimicrobials were proposed to address killing specificity with encouraging results. However, the emergence of target sequence mutations triggered by Cas-cleavage was identified as an escape strategy, posing the risk of generating new antibiotic-resistance gene (ARG) variants. Here, we evaluated an antibiotic re-sensitization strategy based on CRISPR interference (CRISPRi), which inhibits gene expression without damaging target DNA. The resistance to four antibiotics, including last resort drugs, was significantly reduced by individual and multi-gene targeting of ARGs in low- to high-copy numbers in recombinant E. coli. Escaper analysis confirmed the absence of mutations in target sequence, corroborating the harmless role of CRISPRi in the selection of new resistances. E. coli clinical isolates carrying ARGs of severe clinical concern were then used to test the robustness of CRISPRi under different growth conditions. Meropenem, colistin and cefotaxime susceptibility was successfully increased in terms of MIC (up to >4-fold) and growth delay (up to 11-hours) in a medium-dependent fashion. To our knowledge, this is the first demonstration of CRISPRi-mediated re-sensitization to last-resort drugs in clinical isolates. This study laid the foundations for further leveraging CRISPRi as antimicrobial agent or research tool to selectively repress ARGs and investigate resistance mechanisms.

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Global epidemiology of CTX-M-type β-lactam resistance in human and animal

Cited by 12 publications

References 35 publications

The Characteristics of Extended-Spectrum β-Lactamases (ESBLs)-Producing Escherichia coli in Bloodstream Infection

The Characteristics of Extended-Spectrum β-Lactamases (ESBLs)-Producing Escherichia coli in Bloodstream Infection

Non-replicative phage particles delivering CRISPR-Cas9 to target major blaCTX-M variants

Harnessing CRISPR interference to re-sensitize laboratory strains and clinical isolates to last resort antibiotics

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