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Antimicrob Agents Chemother. 2016 November; 60(11): 7000.
Published online 2016 October 21. doi:  10.1128/AAC.01777-16
PMCID: PMC5075131

The Curious Case of TEM-116

LETTER

More than 400 unique TEM β-lactamase variants have been identified (1). Many are derived from one or more mutations at a limited number of positions in TEM-1, the first TEM enzyme to be described (2). Recently, network analysis by Zeil et al. disclosed a second cluster of TEM variants derived from TEM-116 (1). What is so special about this β-lactamase that it has become a second progenitor of this ubiquitous enzyme family?

Since the 1990s, TEM-116 has been described worldwide to occur in a variety of Gram-negative organisms and to be encoded by conjugative plasmids of various sizes (3,8). Although TEM-116 has been characterized microbiologically as an extended-spectrum β-lactamase (ESBL) by some investigators (3, 4, 6, 7), other data do not support this designation based on biochemical and microbiological profiles (9,11). It has been linked on plasmids to the ESBL PER-2, which has an indistinguishable isoelectric point (12) as a possible source of confusion. Other well-established TEM enzymes, whether ESBLs or not, have not given rise to unique clusters of offspring (1). The defining mutations in TEM-116, V84I and A184V, lie in different chains separate from the active site. What is curious about TEM-116 is that blaTEM-1 was engineered in the 1980s to result in precisely these amino acid changes by removing PstI and HincII restriction sites from the wild-type gene to facilitate antibiotic selection using blaTEM in M13 phage and pUC series plasmids as cloning vectors that came to be widely used in molecular biology (13). The 861 nucleotides of some reported blaTEM-116 genes are completely identical to the constructed blaTEM gene in pUC vectors. This is concerning because certain commercial Taq polymerase preparations used in PCRs to characterize β-lactamases have been contaminated with exogenous DNA, in particular with blaTEM-116 DNA, suggesting that their use might lead to the erroneous description of TEM-116 in organisms that do not contain it (14).

Zeil et al. identified more than 50 TEM variants derived from TEM-116 (1). Almost all contain both mutations. Exceptions are TEM-171, with V84I alone, and TEM-181, with A184V alone, which consequently may be intermediate steps between TEM-1 and TEM-116. TEM-116 had to be present in bacteria to evolve as it has. Despite concern about contaminated reagents, the centrality of TEM-116 in the TEM family network, its wide geographical dissemination, and its establishment on multiple plasmids indicate that TEM-116 is now a naturally occurring enzyme.

Funding Statement

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sector.

Footnotes

For the author reply, see doi:10.1128/AAC.01786-16.

REFERENCES

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