CTX-M Enzymes: Origin and Diffusion

Abstract

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.

Molecular screening of antibiotic-resistant determinants among multidrug-resistant clinical isolates of <i>Proteus mirabilis</i> from SouthWest Nigeria

“…17 Another widely spread ESBL group are the CTX-M-type discovered in the 1980s in Munich, Germany from clinical isolate of Escherichia coli and currently five phylogroups exist. 18 They are known to have high hydrolytic property against cefotaxime. 18 Resistance to fluoroquinolones was initially thought to be majorly due to chromosomal mutation involving gyrA and topoisomerase genes until plasmid mediated quinolone resistance genes (PMQR) such as the qnr, qepA and aac (6')-Ib-cr was later reported in 1998.…”

“…18 They are known to have high hydrolytic property against cefotaxime. 18 Resistance to fluoroquinolones was initially thought to be majorly due to chromosomal mutation involving gyrA and topoisomerase genes until plasmid mediated quinolone resistance genes (PMQR) such as the qnr, qepA and aac (6')-Ib-cr was later reported in 1998. 19 Since then PMQR genes have been described in several bacterial isolates particularly members of the Enterobacteriaceae family worldwide.…”

EPIDEMIOLOGICAL OBSERVATORY: spreading of ESBL and carbapenemase positive strains in the period between January 2007 - June 2012, at the Hospital - University Campus - Hospital “Luigi Sacco” in Milan

“…temente nei batteri non fermentanti quali Pseudomonas aeruginosa e Acinetbacter baumannii (5,12). Sebbene i ceppi batterici or ora citati rappresentino i principali produttori di ß-lattamasi a spettro esteso in Europa, studi recenti hanno evidenziato la presenza di ESBL anche in alcuni ceppi emergenti di Salmonella enterica isolati in Italia in cui è stata identificata la presenza del gene bla CTX-M-1 (17).…”

Prevalence of TEM and SHV Genes among Extended Spectrum Beta-Lactamase (ESBL) Producing Escherichia coli Isolates from Infected Diabetic Foot Ulcers in a Tertiary Care Hospital

“…resistance to multiple classes of antibiotics (Manoharan et al, 2011;Gadapelli et al, 2006); At present the number of distinct beta-lactamase gene alleles exceeds 1500 (Catalogued/ curated by G. Jacoby and K. Bush There are many types of ESBLs but most are derived from TEM-1, TEM-2 and SHV-1 beta-lactamase types by mutation with less than 2% difference in amino acid sequences. The other types include CTX-M, few OXA variants (Paterson et al, 2005) In recent times the CTX-M type ESBL genes has emerged as the most common type found among gram negative bacilli worldwide (Bonnet, 2004;Canton et al, 2012).…”