The Role of ISCR1-Borne P(OUT) Promoters in the Expression of Antibiotic Resistance Genes

The ISCR1 (Insertion sequence Common Region) element is the most widespread member of the ISCR family, and is frequently present within γ-proteobacteria that occur in clinical settings. ISCR1 is always associated with the 3′Conserved Segment (3′CS) of class 1 integrons. ISCR1 contains outward-oriented promoters P(OUT), that may contribute to the expression of downstream genes. In ISCR1, there are two P(OUT) promoters named P(CR1-1) and P(CR1-2). We performed an in silico analysis of all publically available ISCR1 sequences and identified numerous downstream genes that mainly encode antibiotic resistance genes and that are oriented in the same direction as the P(OUT) promoters. Here, we showed that both P(CR1-1) and P(CR1-2) significantly increase the expression of the downstream genes bla(CTX-M-9) and dfrA19. Our data highlight the role of ISCR1 in the expression of antibiotic resistance genes, which may explain why ISCR1 is so frequent in clinical settings.