Abstract
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 POUT, that may contribute to the expression of downstream genes. In ISCR1, there are two POUT promoters named PCR1-1 and PCR1-2. 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 POUT promoters. Here, we showed that both PCR1-1 and PCR1-2 significantly increase the expression of the downstream genes blaCTX-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.
Highlights
Antimicrobial resistance is often mediated by the dissemination of antibiotic resistance genes (ARG) that are carried by mobile genetic elements (MGEs) including plasmids, insertion sequences (IS), transposons (Tn) and integron gene cassettes (Partridge, 2011) which are harbored by bacteria across all phyla and environments (Aminov, 2011)
A large percentage of the analyzed ISCR1 elements (n = 946, 84%) carried an adjacent gene oriented in the same direction as the rcr1 encoding transposase gene
Our data highlight the functionality of the two POUT promoters carried by the ISCR1 element
Summary
Antimicrobial resistance is often mediated by the dissemination of antibiotic resistance genes (ARG) that are carried by mobile genetic elements (MGEs) including plasmids, insertion sequences (IS), transposons (Tn) and integron gene cassettes (Partridge, 2011) which are harbored by bacteria across all phyla and environments (Aminov, 2011). Several IS including IS1999, ISEcp, ISKpn (reviewed in Vandecraen et al, 2017) display a complete outwardly oriented functional promoter usually referred as POUT that enhances expression of downstream ARGs. Other IS like IS1 or IS257 only contain the −35 element that generates a hybrid functional promoter when associated with a downstream putative −10 element (Goussard et al, 1991; Simpson et al, 2000). Other IS like IS1 or IS257 only contain the −35 element that generates a hybrid functional promoter when associated with a downstream putative −10 element (Goussard et al, 1991; Simpson et al, 2000) Most often, these IS-borne promoters allow sufficient expression of ARGs to confer the antibiotic resistance phenotype. ISCR1 was first identified as a conserved region disrupting the 3 conserved segment (3 CS) of class 1 integrons
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