Broad-spectrum β-lactamases among Enterobacteriaceae of animal origin: molecular aspects, mobility and impact on public health

Abstract

Broad-spectrum β-lactamase genes (coding for extended-spectrum β-lactamases (ESBLs) and AmpC β-lactamases) have been frequently demonstrated in the microbiota of food-producing animals.This may pose a human health hazard since these genes may be present in zoonotic bacteria, which would cause a direct problem.They can also be present in commensals, which may act as a reservoir of resistance genes for pathogens causing disease both in humans and animals.Broad-spectrum β-lactamase genes are frequently located on mobile genetic elements, such as plasmids, transposons and integrons, which often also carry additional resistance genes.This could limit treatment options for infections caused by broad-spectrum β-lactam-resistant microorganisms.This review addresses the growing burden of broad-spectrum β-lactam resistance among Enterobacteriaceae isolated from food, companion and wild animals worldwide.To explore the human health hazard, the diversity of broad-spectrum β-lactamases among Enterobacteriaceae derived from animals is compared with respect to their presence in human bacteria.Furthermore, the possibilities of the exchange of genes encoding broadspectrum β-lactamases -including the exchange of the transposons and plasmids that serve as vehicles for these genes -between different ecosystems (human and animal) are discussed. CTX-M-type β-lactamasesA third family consists of the CTX-M enzymes, which are also ESBLs and were first isolated in Munich.The designation CTX-M reflects the hydrolytic activity of these β-lactamases against cefotaxime.It appears that the CTX-M-type β-lactamases are closely related to βlactamases of Kluyvera spp.CTX-M enzymes have 40% or less identity with TEM and SHVtype ESBLs.So far, more than 70 CTX-M enzymes have been isolated.They are divided into 5 clusters on the basis of the amino acid sequence: CTX-M-1, CTX-M-2, CTX-M-8, CTX-M-9 and CTX-M-25 (Gupta, 2007;Paterson & Bonomo, 2005). OXA-type β-lactamasesMost OXA-type β-lactamases, so named because of their oxacillin-hydrolizing capabilities, do not hydrolyse extended-spectrum cephalosporins and are not regarded as ESBLs.The exceptions to this rule are OXA-10 and OXA-13 to OXA-19 (Toleman et al., 2003).The evolution of ESBL OXA-type β-lactamases from parent enzymes with narrow spectra has many parallels with the evolution of TEM-and SHV-type ESBLs.Other examples of ESBLs PER (Pseudomonas extended-resistant), VEB (Vietnam extended-spectrum β-lactamase), BES (Brazil extended-spectrum), GES (Guiana extended-spectrum), TLA (named after Tlahuicas Indians), SFO (Serratia fonticola) and IBC (integron-borne cephalosporinase) are other examples of ESBLs that have been discovered (Gupta, 2007;Jacoby, 2006;Paterson & Bonomo, 2005).These enzymes are not so common among Enterobacteriaceae as the ESBLs described above.