Evolution of TEM-Type Extended-Spectrum β-Lactamases in Clinical Enterobacteriaceae Strains in Poland

Abstract

Seventeen extended-spectrum ␤-lactamase (ESBL)-producing isolates of the family Enterobacteriaceae recovered from 1998 to 2000 in hospitals of five different cities in Poland were analyzed. They expressed several TEM-type ESBLs, TEM-4, TEM-29, TEM-85, TEM-86, TEM-93, and TEM-94. TEM-85 (L21F, R164S, E240K, T265M), TEM-86 (L21F, R164S, A237T, E240K, T265M), TEM-93 (M182T, G238S, E240K), and TEM-94 (L21F, E104K, M182T, G238S, T265M) were identified for the first time. Including the enzymes described earlier, TEM-47, TEM-48, TEM-49, and TEM-68, the group of known ESBLs of the TEM family produced by enterobacteria in Polish hospitals has increased to 10 variants. Comparative sequence analysis of the genes coding for all these ␤-lactamases revealed a view of their possible evolution, which, apart from the gradual acquisition of various mutations, could also have involved recombination events. Two different bla TEM-1 gene alleles were precursors of the ESBL genes: bla TEM-1A , which was the ancestor of bla TEM-93 , and bla TEM-1F , from which all the remaining genes originated. The evolution of the bla TEM-1F -related genes most probably consisted of three major separate lineages, one of which, including bla TEM-4 , bla TEM-47 , bla TEM-48 , bla TEM-49 , bla TEM-68 , and bla TEM-94 , was highly structured itself and could have been initiated by the bla TEM-25 gene, identified exclusively in France so far. Plasmid fingerprinting analysis revealed a high degree of diversity of plasmids carrying related bla TEM genes, which suggested either the intense diversification or transposition of bla TEM genes between different plasmids or some contribution of convergent evolution. The results of this study clearly demonstrate that the environment of Polish hospitals has been highly favorable for the rapid evolution of ESBLs.

Scientific Opinion on the public health risks of bacterial strains producing extended-spectrum β-lactamases and/or AmpC β-lactamases in food and food-producing animals

“…These ESBLs developed by mutations of the broad spectrum TEM-1 and SHV-1 and 2 genes were transferred between bacteria by plasmids, which were in turn spread by clonal distribution between hospitals and countries through patient mobility (Baraniak et al, 2005;Damjanova et al, 2007;Jacoby and Munoz-Price, 2005;Paterson and Bonomo, 2005).…”

Fitness Trade-Offs inblaTEMEvolution

“…An obvious prediction for ESBL bla TEM alleles is that they would either co-occur with bla TEM-1 or replace it as the most frequently encountered allele in environments where cephalosporins are heavily used. However, neither of these patterns has been observed among clinical populations of microorganisms, and bla TEM-1 is still the most commonly occurring allele in many microbial populations where cephalosporin resistance has been selected for (1,3,9,12,13,17,19,20,30,34). The high frequency of bla TEM-1 in microbial populations is counterintuitive, because the alleles descended from bla TEM-1 confer both the advantageous cephalosporin resistance phenotypes and the ancestral penicillin resistance phenotype, which should promote their fixation in microbial populations.…”

Antibiotic-Resistant Klebsiella pneumoniae and Escherichia coli High-Risk Clones and an IncFII k Mosaic Plasmid Hosting Tn 1 ( bla TEM-4 ) in Isolates from 1990 to 2004

“…The ⌬Tn1 (bla TEM-4 ) sequence was similar to that of other unrelated plasmids from our institution, Poland, or the United Kingdom (GenBank accession numbers HQ659758 and AM261760). Similar nucleotide polymorphisms of promoters and transposon sequences of ⌬Tn1 (bla TEM-4 ) and Tn1 (bla TEM-2 ) suggest a common origin, as described for other bla TEM ESBLs (5,8,28). Note that Tn1 (bla TEM-4 ) was found on K. pneumoniae (ST13 and ST37) and E. coli (ST131, ST117, and ST127) high-risk clones, all emerging in the 21st century as major drivers of ESBL, acquired AmpC, and carbapenemase spread (29)(30)(31)(32)(33)(34).…”

“…TEM-4 producers were reported first in France in 1986 and later in Spain, Poland, and Tunisia (5,(11)(12)(13)(14)(15)(16)(17)(18). Both strains and plasmids of Klebsiella pneumoniae carrying bla have caused nosocomial and community outbreaks, some of them being persistently recovered in hospitals from different countries (12,17,19).…”

“…Very few bla TEM genes (bla , bla , bla , bla , bla , bla , and bla TEM-52 ) have successfully been spread (1)(2)(3)(4)(5), but the genetic context has only been characterized for three of them (e.g., bla TEM-3, bla TEM-24, and bla TEM-52 ) (6)(7)(8). These bla TEM genes are part of the Tn3 elements, namely, Tn3 (bla TEM-1a ), Tn2 (bla TEM-1b ), and Tn1/Tn801 (bla TEM-2 ), which are located on highly transmissible plasmids (8,9).…”