Why the Extended-Spectrum β-Lactamases SHV-2 and SHV-5 Are “Hypersusceptible” to Mechanism-Based Inhibitors

Avibactam and inhibitor resistant SHV β - lactamases 1 2

A Review of SHV Extended-Spectrum β-Lactamases: Neglected Yet Ubiquitous

β-lactamases are the primary cause of resistance to β-lactams among members of the family Enterobacteriaceae. SHV enzymes have emerged in Enterobacteriaceae causing infections in health care in the last decades of the Twentieth century, and they are now observed in isolates in different epidemiological settings both in human, animal and the environment. Likely originated from a chromosomal peni...

Use of novel boronic acid transition state inhibitors to probe substrate affinity in SHV-type extended-spectrum beta-lactamases.

Boronic acid transition state inhibitors (BATSIs) with R1 side chains of cefotaxime and ceftazidime were assayed against SHV-1, SHV-2, SHV-5, D104K, and D104K G238S beta-lactamases. The D104K variant was the most susceptible to inhibition by the ceftazidime BATSI (Ki, 730+/-80 nM), while the D104K G238S variant was the most susceptible to the cefotaxime BATSI (Ki, 1.1+/-0.2 microM).

Evolution and spread of SHV extended-spectrum beta-lactamases in gram-negative bacteria.

Resistance to beta-lactam antibiotics has been a problem for as long as these drugs have been used in clinical practice. In clinically significant bacteria the most important mechanism of resistance is the production of one or more beta-lactamases, enzymes that hydrolyse the beta-lactam bond characteristic of this family of antibiotics. Prominent among the beta-lactamases produced by the Entero...

Survey and molecular genetics of SHV beta-lactamases in Enterobacteriaceae in Switzerland: two novel enzymes, SHV-11 and SHV-12.

Sixty isolates of Enterobacteriaceae resistant to beta-lactam antibiotics were collected over a period of 2 years in Switzerland and screened by hybridization for the carriage of SHV genes. Thirty-four positive strains were found, and their SHV genes were amplified and sequenced. SHV extended-spectrum beta-lactamases (ESBLs) were found: 13 strains contained SHV-2a, 12 harbored SHV-2, and SHV-5 ...