1. The spread of CTX-M-type extended-spectrum β-lactamases
G.M. Rossolini, M.M. D'Andrea, C. Mugnaioli 
Clinical Microbiology and Infection 
Volume 14, Pages (January 2008)
DOI: /j x
Copyright © 2008 European Society of Clinical Infectious Diseases Terms and Conditions

2. Fig. 1
The six known sub-lineages (or groups) of CTX-M-type β-lactamases, shown in a tree diagram that reflects similarity at the amino-acid sequence level. Filled triangles at the end of each branch indicate the presence of minor allelic variants within the corresponding group. The tree was constructed with the TREEVIEW program ( based on a multiple sequence alignment of the publicly available CTX-M sequences ( The degree of amino-acid sequence divergence among different groups ranges from 9.3% to 32% (or 25%, not considering the most divergent CTX-M-45 enzyme), being ≤3.5% within each group. CTX-M-14 is identical to CTX-M-18, and only the former is listed. Toho-1 corresponds to CTX-M-44, Toho-2 to CTX-M-45, UOE-1 to CTX-M-15, and UOE-2 and Toho-3 to CTX-M-14.
Clinical Microbiology and Infection  , 33-41DOI: ( /j x)
Copyright © 2008 European Society of Clinical Infectious Diseases Terms and Conditions

3. Fig. 2
Examples of different genetic contexts of blaCTX-M genes. (a) blaCTX-M-I5 located downstream of ISEcp1. A similar arrangement has also been observed with several other blaCTX-M allotypes of the CTX-M-1, CTX-M-2, CTX-M-9 and CXT-M-25 groups [4,33]. (b) blaCTX-M-2 located downstream of ISCR1, in association with a class 1 integron structure [4,34]. A similar arrangement has also been observed with several other blaCTX-M allotypes of the CTX-M-2 and CXT-M-9 groups [34]. (c) blaCTX-M-10 in an unusual genetic context, associated with phage-related genes and insertion sequences [35].
Clinical Microbiology and Infection  , 33-41DOI: ( /j x)
Copyright © 2008 European Society of Clinical Infectious Diseases Terms and Conditions

4. Fig. 3
Modulation of the substrate spectrum of CTX-M-type enzymes by point mutations. The structure of a CTX-M-type enzyme (CTX-M-9; PDB entry 1YLJ) is shown here as a ribbon diagram generated with the DEEPVIEW program ( As with other serine β-lactamases, the overall molecular fold consists of an α-helical domain (on the left side) and a mixed α/β-domain (on the right side). The β-lactam-binding site, indicated by an arrow, is located in a cleft between the two domains. positions 167 and 240, where amino-acid substitutions enhancing ceftazidimase activity occur, are located either in the Ω-loop (in green, at the bottom of the binding site) or in the terminal part of the B3 β-strand (β3, in red, on the right side of the binding site), and are shown by red dots. The active site serine residue (Ser*) in the active site, located at the end of H2 α-helix (a2, in yellow), is also shown. The Asp240 → Gly substitution should increase the flexibility of the B3 β-strand, rendering the active site more accessible to the bulkier ceftazidime molecule [9]. The Pro167 → Ser substitution in the Ω-loop is thought to modify the mode of interaction of β-lactams with the binding site, allowing better recognition of ceftazidime but impairing recognition of some other substrates [14].
Clinical Microbiology and Infection  , 33-41DOI: ( /j x)
Copyright © 2008 European Society of Clinical Infectious Diseases Terms and Conditions

5. Fig. 4
World map showing locations where clinical isolates of Enterobacteriaceae producing CTX-M-type extended-spectrum β-lactamases have been reported. Data are according to Reference [4] and the subsequent literature available on the PubMed database (
Clinical Microbiology and Infection  , 33-41DOI: ( /j x)
Copyright © 2008 European Society of Clinical Infectious Diseases Terms and Conditions