CTX-M Enzymes: Origin and Diffusion

By R. Cantón, J. González-Alba, J. Galán. Front. Microbio., 2012

940 citations recorded by the source corpus.

CTX-M β-lactamases are considered a paradigm in the evolution of a resistance mechanism. Incorporation of different chromosomal blaCTX-M related genes from different species of Kluyvera has derived in different CTX-M clusters. In silico analyses have shown that this event has occurred at least nine times; in CTX-M-1 cluster (3), CTX-M-2 and CTX-M-9 clusters (2 each), and CTX-M-8 and CTX-M-25 clusters (1 each). This has been mainly produced by the participation of genetic mobilization units such as insertion sequences (ISEcp1 or ISCR1) and the later incorporation in hierarchical structures associated with multifaceted genetic structures including complex class 1 integrons and transposons. The capture of these blaCTX-M genes from the environment by highly mobilizable structures could have been a random event. Moreover, after incorporation within these structures, β-lactam selective force such as that exerted by cefotaxime and ceftazidime has fueled mutational events underscoring diversification of different clusters. Nevertheless, more variants of CTX-M enzymes, including those not inhibited by β-lactamase inhibitors such as clavulanic acid (IR-CTX-M variants), only obtained under in in vitro experiments, are still waiting to emerge in the clinical setting. Penetration and the later global spread of CTX-M producing organisms have been produced with the participation of the so-called “epidemic resistance plasmids” often carried in multi-drug resistant and virulent high-risk clones. All these facts but also the incorporation and co-selection of emerging resistance determinants within CTX-M producing bacteria, such as those encoding carbapenemases, depict the currently complex pandemic scenario of multi-drug resistant isolates.

Subfields: Genetics, Molecular Biology, Molecular Medicine

View Paper: https://www.semanticscholar.org/paper/533fced1b3e85442b206e7d474f8d1f1b6226692

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Genetics

1. P. Bradford
2. K. Bush
3. P. Nordmann
4. L. Poirel

In Molecular Biology

1. K. Bush
2. L. Poirel
3. P. Nordmann
4. F. Cabello
5. P. Bradford
6. John Penders
7. J. Madec

In Molecular Medicine

1. L. Poirel
2. P. Nordmann
3. K. Bush
4. P. Bradford
5. F. Cabello
6. J. Madec
7. J. Pitout
8. F. Codjoe

Citations in the corpus

• Antimicrobial use in aquaculture re-examined: its relevance to antimicrobial resistance and to animal and human health. (2013, background): “…encountered in the aquatic environment in fish intestines and an opportunistic human pathogen (Tables 2 and 3) (Decousser et al., 2001; Sarria et al., 2001; Humeniuk et al., 2002; Rodriguez et al., 2004; Cantón and Coque, 2006; Navarrete et al., 2008; Rossolini et al., 2008; Cantón et al., 2012).”
• Epidemiology of β-Lactamase-Producing Pathogens (2020, background): “marcescens, as well as several species of nonfermenters (153, 157).”
• Dissemination of Antimicrobial Resistance in Microbial Ecosystems through Horizontal Gene Transfer (2016, background): “This is well demonstrated by the blaCTX−M ESBL genes, which have disseminated to various narrow and broad host range plasmids within Enterobacteriaceae, as well as to other opportunistic human pathogens (Canton et al., 2012).”
• Trends in Human Fecal Carriage of Extended-Spectrum β-Lactamases in the Community: Toward the Globalization of CTX-M (2013, background): “the Kluyvera genus (11), have repeatedly moved to plasmids well adapted to E.”
• Antimicrobial Resistance in Escherichia coli (2018, background): “ESBL genes are associated with several insertion sequences (ISs), such as ISEcp1, ISCR1, IS26, and IS10, transposons such as Tn2, and integrons (43, 45, 46).”