<P> Penicillinase was the first β - lactamase to be identified . It was first isolated by Abraham and Chain in 1940 from Gram - negative E. coli even before penicillin entered clinical use, but penicillinase production quickly spread to bacteria that previously did not produce it or produced it only rarely . Penicillinase - resistant beta - lactams such as methicillin were developed, but there is now widespread resistance to even these . </P> <P> Among Gram - negative bacteria, the emergence of resistance to expanded - spectrum cephalosporins has been a major concern . It appeared initially in a limited number of bacterial species (E. cloacae, C. freundii, S. marcescens, and P. aeruginosa) that could mutate to hyperproduce their chromosomal class C β - lactamase . A few years later, resistance appeared in bacterial species not naturally producing AmpC enzymes (K. pneumoniae, Salmonella spp., P. mirabilis) due to the production of TEM - or SHV - type ESBLs (extended spectrum beta lactamases). Characteristically, such resistance has included oxyimino - (for example ceftizoxime, cefotaxime, ceftriaxone, and ceftazidime, as well as the oxyimino - monobactam aztreonam), but not 7 - alpha - methoxy - cephalosporins (cephamycins; in other words, cefoxitin and cefotetan); has been blocked by inhibitors such as clavulanate, sulbactam or tazobactam and did not involve carbapenems and temocillin . Chromosomal - mediated AmpC β - lactamases represent a new threat, since they confer resistance to 7 - alpha - methoxy - cephalosporins (cephamycins) such as cefoxitin or cefotetan but are not affected by commercially available β - lactamase inhibitors, and can, in strains with loss of outer membrane porins, provide resistance to carbapenems . </P> <P> Members of the family commonly express plasmid - encoded β - lactamases (e.g., TEM - 1, TEM - 2, and SHV - 1), which confer resistance to penicillins but not to expanded - spectrum cephalosporins . In the mid-1980s, a new group of enzymes, the extended - spectrum β - lactamases (ESBLs), was detected (first detected in 1979). The prevalence of ESBL - producing bacteria have been gradually increasing in acute care hospitals . ESBLs are beta - lactamases that hydrolyze extended - spectrum cephalosporins with an oxyimino side chain . These cephalosporins include cefotaxime, ceftriaxone, and ceftazidime, as well as the oxyimino - monobactam aztreonam . Thus ESBLs confer multi-resistance to these antibiotics and related oxyimino - beta lactams . In typical circumstances, they derive from genes for TEM - 1, TEM - 2, or SHV - 1 by mutations that alter the amino acid configuration around the active site of these β - lactamases . A broader set of β - lactam antibiotics are susceptible to hydrolysis by these enzymes . An increasing number of ESBLs not of TEM or SHV lineage have recently been described . The ESBLs are frequently plasmid encoded . Plasmids responsible for ESBL production frequently carry genes encoding resistance to other drug classes (for example, aminoglycosides). Therefore, antibiotic options in the treatment of ESBL - producing organisms are extremely limited . Carbapenems are the treatment of choice for serious infections due to ESBL - producing organisms, yet carbapenem - resistant (primarily ertapenem resistant) isolates have recently been reported . ESBL - producing organisms may appear susceptible to some extended - spectrum cephalosporins . However, treatment with such antibiotics has been associated with high failure rates . </P> <P> TEM - 1 is the most commonly encountered beta - lactamase in Gram - negative bacteria . Up to 90% of ampicillin resistance in E. coli is due to the production of TEM - 1 . Also responsible for the ampicillin and penicillin resistance that is seen in H. influenzae and N. gonorrhoeae in increasing numbers . Although TEM - type beta - lactamases are most often found in E. coli and K. pneumoniae, they are also found in other species of Gram - negative bacteria with increasing frequency . The amino acid substitutions responsible for the extended - spectrum beta lactamase (ESBL) phenotype cluster around the active site of the enzyme and change its configuration, allowing access to oxyimino - beta - lactam substrates . Opening the active site to beta - lactam substrates also typically enhances the susceptibility of the enzyme to β - lactamase inhibitors, such as clavulanic acid . Single amino acid substitutions at positions 104, 164, 238, and 240 produce the ESBL phenotype, but ESBLs with the broadest spectrum usually have more than a single amino acid substitution . Based upon different combinations of changes, currently 140 TEM - type enzymes have been described . TEM - 10, TEM - 12, and TEM - 26 are among the most common in the United States . The term TEM comes from the name of the Athenian patient (Temoniera) from which the isolate was recovered in 1963 . </P>

Where is beta lactamase found in the cell