Dissemination of Clonally Related Escherichia coli Strains Expressing Extended-Spectrum β-Lactamase CTX-M-15

Abstract

We analyzed 43 CTX-M-15-producing Escherichia coli isolates and 6 plasmids encoding the bla CTX-M-15 gene from Canada, India, Kuwait, France, Switzerland, Portugal, and Spain.Most isolates belonged to phylogroups B2 (50%) and D (25%).An EC-B2 strain of clonal complex sequence type (ST) 131 was detected in all countries; other B2 isolates corresponded to ST28, ST405, ST354, and ST695 from specifi c areas.EC-D strains were clonally unrelated but isolates from 3 countries belonged to ST405.All CTX-M-15 plasmids corresponded to IncFII group with overrepresentation of 3 HpaI-digested plasmid DNA profi les (A, B and C; 85-120kb, similarity >70%).Plasmid A was detected in EC-B2 strains (ST131, ST354, or ST405), plasmid C was detected in B2 and D strains, and plasmid B was confi ned to worldwide-disseminated ST131.Most plasmids contained bla OXA-1 , aac(6′)-Ib-cr, and bla TEM-1 .Worldwide dissemination of CTX-M-15 seems to be determined by clonal complexes ST131 and ST405 and multidrug-resistant IncFII plasmids.P lasmid-mediated CTX-M type expanded-spectrum β- lactamases (ESBLs), which have been extensively reported for the past 10 years, are detected mostly in community-acquired pathogens and are associated mainly with Escherichia coli.These β-lactamases compromise the ef-fi cacy of all β-lactams, except carbapenems and cephamycins, and are associated with many non-β-lactam resistance markers because of their locations on plasmids.Therefore, they may constitute a real threat for treating communityacquired E. coli-mediated urinary tract infections (1,2).Different variants of CTX-M ESBLs are grouped in 5 clusters, although their distribution varies greatly depending on the geographic area (www.lahey.org/studies/webt.htm).CTX-M-15, which was fi rst detected in isolates from India in 2001 (3), is now recognized as the most widely distributed CTX-M enzyme.It is derived from CTX-M-3 by 1 amino acid substitution at position 240 (Asp-240 → Gly), which apparently confers an increased catalytic activity to ceftazidime (4).Clonal outbreaks of CTX-M-15-producing Enterobacteriaceae have been reported in France, Italy, Spain, Portugal, Austria, Norway, the United Kingdom, Tunisia, South Korea, and Canada, and E. coli is the most frequently involved species.Within E. coli, CTX-M-15-producing strains of the B2 phylogenetic group are commonly found and frequently harbor multidrug resistance and virulence determinants (5-18).Plasmids encoding bla CTX-M-15 have been isolated from clinical isolates in France, Spain, Portugal, the United Kingdom, Canada, India, Pakistan, South Korea, Taiwan, the United Arabic Emirates, and Honduras (5-8, 10,11,15,19,20).Plasmid characterization, which has only been accomplished for those plasmids from Canada, France, Spain, and the United Kingdom, classifi ed most of them as members of incompatibility group FII (5,7,8,17,19).Lack of detailed studies on isolates expressing particular CTX-Ms from different geographic areas has precluded identifi cation of factors involved in recent and worldwide Dissemination of Clonally Related Escherichia coli Strains Expressing Extended-Spectrum β-Lactamase