FIG. 4.
Proposed model of ISCR19-mediated mobilization of blaOXA-18 and genesis of a blaOXA-18-containing intI1 complex class 1 integron. The construction of blaOXA-18-containing complex class 1 integrons has been inspired from the model proposed by Toleman et al. Several steps are necessary. (A) Insertion of ISCR19* into a class 1 integrase gene. Aberrant RC replication of the ISCR19* element (inserted into the int1 gene) generates a transposition intermediate starting at oriIS, ending at another terIS, and then its cognate terIS at terIS1, located inside the aac6′-Ib gene. (B) This intermediate then transposes adjacent to the blaOXA-18 gene in another location. (C) A second aberrant RC replication event produces circular intermediates that now include the blaOXA-18 gene. (D) These circular intermediates may then be rescued by recombination events between aac6′-Ib or integrase genes on another a class 1 integron already including a copy of ISCR19, generating the blaOXA-18-containing complex integron. Boxes represent the ORFs of the genes, with arrows indicating the direction of their transcription. The transposase gene of the ISCR19 elements are dotted, the integrase gene is shaded in gray, and the blaOXA-18 gene is black. The integrase-specific recombination sites are indicated as black dots. oriIS is represented as an black triangle, terIS is represented as a gray triangle, and terIS1, -2, and -3 represent secondary terIS (open triangles). The vertical arrow in panel D indicates the deletion event that occurred fusing the 5′CS sequence with that of tnpA of ISCR19*.