Sulfhydryl variable beta-lactamase (SHV) (SHV)

Sulfhydryl variable beta-lactamase (SHV) is a clinically significant Ambler Class A serine beta-lactamase enzyme primarily identified in Gram-negative pathogens such as Klebsiella pneumoniae (Bush & Jacoby, 2010). Its primary biological function is the hydrolysis of the beta-lactam ring in antibiotics, which neutralizes the drug's ability to inhibit bacterial cell wall synthesis (Liakopoulos et al., 2016). While the ancestral SHV-1 enzyme mainly targets penicillins, numerous mutations have given rise to Extended-Spectrum Beta-Lactamase (ESBL) variants that degrade third-generation cephalosporins and monobactams (Drawz & Bonomo, 2010). These enzymes are major drivers of antibiotic resistance in hospital-acquired infections, including pneumonia, urinary tract infections, and bloodstream infections (StatPearls, 2023). To combat this resistance, SHV is targeted by beta-lactamase inhibitors such as clavulanic acid, tazobactam, and newer non-beta-lactam inhibitors like avibactam (PubMed, 2022). These inhibitors bind to the enzyme's active site, preventing it from destroying co-administered antibiotics and thereby restoring their therapeutic efficacy. The ongoing evolution of SHV into inhibitor-resistant forms (IR-SHV) remains a significant hurdle in infectious disease management, necessitating the continuous development of next-generation antimicrobial agents (NCBI, 2021).

Other names

Sulfhydryl variable beta-lactamaseSHV-type beta-lactamaseSHV-1Class A beta-lactamase SHVSulfhydryl variable enzyme

Beta-lactamase inhibitors target the SHV enzyme through several mechanisms: 1) Irreversible suicide inhibition where the inhibitor forms a stable covalent acyl-enzyme intermediate (e.g., clavulanic acid, tazobactam); 2) Reversible covalent inhibition using diazabicyclooctane (DBO) or boronate scaffolds that mimic the transition state (e.g., avibactam, vaborbactam); 3) Competitive inhibition by occupying the active site and preventing substrate access (Drawz & Bonomo, 2010; Bush, 2018).