4.3 Mutations in CTX-M-type ESBLs

CTX-M-type ESBLs preferentially act on certain cephalosporin antibiotics. Cefotaxime is easily recognised and inactivated by CTX-M-type ESBLs while the bulkier cephalosporin ceftazidime is poorly recognised by CTX-M-type ESBLs (Bonnet, 2004). As a consequence, infections caused by bacteria that produce CTX-M-type ESBLs can be treated with ceftazidime. This specificity is based on the structure of the CTX-M β-lactam binding site which only allows the efficient recognition of penicillins, first-generation cephalosporins and cefotaxime (Figure 14) (Chen et al., 2005).

The specificity of CTX-M-type ESBLs can be modified by point mutations which improve the specificity of CTX-M-type ESBLs for ceftazidime. One of these mutations is indicated on Figure 14 (Cartelle et al., 2004). Altering this amino acid allows the bulkier ceftazidime to be more easily accommodated in the β-lactam binding site (Chen et al., 2005). Infections caused by bacteria producing this mutated version of the CTX-M-type ESBL are not treatable with ceftazidime. This CTX-M variant has been isolated from clinical strains of E. coli (Cartelle et al., 2004) and has probably been selected for the increasing use of ceftazidime in clinical practice.