SHV-12 serine beta-lactamase (SHV-12)

SHV-12 is a clinically significant extended-spectrum beta-lactamase (ESBL) belonging to the Ambler Class A serine beta-lactamases [PMID: 20435871]. It is a variant of the parent SHV-1 enzyme, distinguished by key amino acid substitutions—most notably Gly238Ser and Glu240Lys—that expand its substrate range to include third-generation cephalosporins and monobactams [PMID: 11134456]. This enzyme is frequently encoded on plasmids and is widely distributed among Gram-negative pathogens like Klebsiella pneumoniae and Escherichia coli, facilitating the spread of multidrug resistance [PMID: 15980339]. SHV-12 functions by utilizing a catalytic serine residue to hydrolyze the beta-lactam ring of antibiotics, thereby neutralizing the drug before it can inhibit bacterial cell wall synthesis [UniProt: P0AD64]. To overcome this resistance, therapeutic strategies employ beta-lactamase inhibitors such as tazobactam or avibactam, which bind to the enzyme's active site and restore the activity of the companion beta-lactam antibiotic [PMID: 29070403]. The presence of SHV-12 in clinical isolates often necessitates the use of carbapenems or newer inhibitor combinations, making it a critical target in infectious disease management.

Other names

Sulfhydryl variable 12SHV-12 extended-spectrum beta-lactamaseblaSHV-12Beta-lactamase SHV-12

Beta-lactamase inhibitors act by forming a stable, often covalent, acyl-enzyme intermediate with the catalytic serine residue (Ser70) of the SHV-12 enzyme, effectively blocking the active site and preventing the hydrolysis of beta-lactam antibiotics [PMID: 29070403].