Key points are not available for this paper at this time.
The group of plasmid-mediated SHY -lactamases includes SHY-1 and at least twenty-three variants, most of which possess extended-spectrum (ES) activity against the newer broad-spectrum cephalosporins. Their likely ancestor is a chromosomal penicillinase of Klebsiella pneumoniae. SHY enzymes belong to the molecular class A of serine -lactamases and share extensive functional and structural similarity with TEM -lactamases. The three-dimensional structure of the SHY-1 -lactamase possesses an active site wider than that ofTEM-1 -lactamase by 0.7 to 1.2 A. This results in subtle, yet important, differences in the positioning of critical active-site residues. SHY-1 -lactamase behaves as a typical penicillinase hydrolyzing penicillins and early generation cephalosporins. SHY-1 -lactamase has spread, via plasmids, to virtually all enterobacterial species but is encountered mostly in K. pneumoniae. ES SHY -lactamases are found with increasing frequency in K. pneumoniae and other enterobacterial isolates and are now considered the most prevalent ES-lactamases. These ES SHY -lactamases confer a wide spectrum of resistance to -lactams, including the new generation cephalosporins and monobactams, and are usually encoded by self-transmissible multi-resistant plasmids that are highly mobile. Extension of the hydrolytic spectrum of ES SHY enzymes to include oximino--lactams is seen as a result of substitutions of critical amino acid residues that alter the properties of the active site. These mutational changes, however, result in diminished hydrolytic activity against penicillins and an increased susceptibility to mechanism-based inhibitors. Understanding the substrate evolution, properties and modes of spread of these clinically important -lactamases can help in formulating effective antibiotic policies and developing new antimicrobial agents.
Tzouvelekis et al. (1999) studied this question.