Two New SGI1-LK Variants Found in Proteus mirabilis and Evolution of the SGI1-HKL Group of Salmonella Genomic Islands

Abstract

Integrative mobilizable elements belonging to the SGI1-H, -K, and -L Salmonella genomic island 1 (SGI1) variant groups are distinguished by the presence of an alteration in the backbone (IS1359 replaces 2.8 kb of the backbone extending from within traN [S005] to within S009). Members of this SGI1-HKL group have been found in Salmonella enterica serovars and in Proteus mirabilis Two novel variants from this group, designated SGI1-LK1 and SGI1-LK2, were found in the draft genomes of antibiotic-resistant P. mirabilis isolates from two French hospitals. Both variants can be derived from SGI1-PmGUE, a configuration found previously in another P. mirabilis isolate from France. SGI1-LK1 could arise via an IS26-mediated inversion in the complex class 1 integron that duplicated the IS26 element and the target site in IS6100 SGI1-LK1 also has a larger 8.59-kb backbone deletion extending from traN to within S013 and removing traG and traH. However, SGI1-LK1 was mobilized by an IncC plasmid. SGI1-LK2 can be derived from a hypothetical progenitor, SGI1-LK0, that is related to SGI1-PmGUE but lacks the aphA1 gene and one copy of IS26. The integron of SGI1-LK2 could arise via deletion of DNA adjacent to an IS26 and a deletion occurring via homologous recombination between duplicated copies of part of the integron 3'-conserved segment. SGI1-K can also be derived from SGI1-LK0. This would involve an IS26-mediated deletion and an inversion via homologous recombination of a segment between inversely oriented IS26s. Similar events can explain the configuration of the integrons in other SGI1-LK variants.IMPORTANCE Members of the SGI1-HKL subgroup of SGI1-type integrative mobilizable elements have a characteristic alteration in their backbone. They are widely distributed among multiply antibiotic-resistant Salmonella enterica serovars and Proteus mirabilis isolates. The SGI1-K type, found in the globally disseminated multiply antibiotic-resistant Salmonella enterica serovar Kentucky clone ST198 (sequence type 198), and various configurations in the original SGI1-LK group, found in other multiresistant S. enterica serovars and Proteus mirabilis isolates, have complex and highly plastic resistance regions due to the presence of IS26 However, how these complex forms arose and the relationships between them had not been analyzed. Here, a hypothetical progenitor, SGI1-LK0, that can be formed from the simpler SGI1-H is proposed, and the pathways to the formation of new variants, SGI1-LK1 and SGI1-LK2, found in P. mirabilis and other reported configurations via homologous recombination and IS26-mediated events are proposed. This led to a better understanding of the evolution of the SGI1-HKL group.

Keywords: IS26; Proteus mirabilis; SGI1; Salmonella genomic island 1; evolution.

FIG 1

Schema of SGI1 variants. The chromosomal genes are in pink, the backbones of SGI1 variants are in blue, and the multiple-antibiotic-resistance (MAR) region and IS1359 are represented in yellow. attL and attR are the left and right attachment sites, respectively. The position of the class 1 integron is indicated by the 5-bp duplication (ACTTG). (A) SGI1 and SGI1-HKL variant group. SGI1 has already been reported to be inserted at the 3′-end of the trmE gene upstream of the following chromosomal (Chr) genes: the int2 gene (retron phage gene) in S. Typhimurium DT104, the yidY gene of S. enterica, and the hipB gene of Proteus mirabilis. The SGI1-H, -K, and -L groups were previously reported to be inserted at the 3′-end of the trmE gene upstream of the following chromosomal genes: the yidY gene in S. enterica, the hipB gene in P. mirabilis, and the permease gene in Morganella morganii. *, the 5′-end of S044 is deleted in SGI1-K variants. (B) SGI1-LK1 variant. The SGI1-LK1 variant is inserted at the 3′-end of the trmE gene upstream of the hipB gene of P. mirabilis.

FIG 2

The MAR region of SGI1-PmGUE and generation of the MAR region of SGI1-LK1. Horizontal arrows indicate genes and open reading frames (ORFs) with their transcriptional orientation. The segments with genes and ORFs present in SGI1-K are in blue, those present in SGI1-L are in green, and those corresponding to IS26-aphA1 are in orange. Backbone genes are represented in yellow. Black arrows represent 5′ conserved segments and 3′ conserved segments of integrons. The thick vertical bars indicate the inverted repeats (IRs) of integrons (IRi) and transposons (IRt). Resistance genes are shown with red arrows, and ovals represent attC sites. The insertion sequences (ISs) are represented by hatched arrows and by purple arrows for IS26. The IS26s predicted to cause rearrangements are circled. Their IRs are represented by thin vertical bars.

FIG 3

The MAR region of SGI1-LK2 and its generation from the MAR region of SGI1-PmGUE and/or of the proposed progenitor SGI1-LK0. Horizontal arrows indicate genes and ORFs with their transcriptional orientation. The segments with genes and ORFs present in SGI1-K are in blue, those present in SGI1-L are in green, and those corresponding to IS26-aphA1 are in orange. Backbone genes are represented in yellow. Black arrows represent 5′ conserved segments and 3′ conserved segments of integrons. The thick vertical bars indicate the IRs of integrons (IRi) and transposons (IRt). Resistance genes are shown with red arrows, and ovals represent attC sites. The ISs are represented by hatched arrows and by purple arrows for IS26. The IS26s predicted to cause rearrangements are circled. Their IRs are represented by thin vertical bars. HR, homologous recombination.

FIG 4

The MAR region of SGI1-K and its generation from the MAR region of the proposed progenitor SGI1-LK0. Horizontal arrows indicate genes and ORFs with their transcriptional orientation. The segments with genes and ORFs present in SGI1-K are in blue, those present in SGI1-L are in green, and those corresponding to IS26-aphA1 are in orange. Backbone genes are represented in yellow. Black arrows represent 5′ conserved segments and 3′ conserved segments of integrons. The thick vertical bars indicate the IRs of integrons (IRi) and transposons (IRt). Resistance genes are shown with red arrows, and ovals represent attC sites. The ISs are represented by hatched arrows and by purple arrows for IS26. The IS26s predicted to cause rearrangements are circled. Their IRs are represented by thin vertical bars. HR, homologous recombination.

FIG 5

Relationship between the MAR regions of SGI1-H and SGI1-L variants and the MAR region of SGI1-PmGUE. Horizontal arrows indicate genes and ORFs with their transcriptional orientation. The segments with genes and ORFs present in SGI1-K are in blue, those present in SGI1-L are in green, and those corresponding to IS26-aphA1 are in orange. Backbone genes are represented in yellow. Black arrows represent 5′ conserved segments and 3′ conserved segments of integrons. The thick vertical bars indicate the IRs of integrons (IRi) and transposons (IRt). Resistance genes are shown with red arrows, and ovals represent attC sites. The ISs are represented by hatched arrows and by purple arrows for IS26. Their IRs are represented by thin vertical bars. HR, homologous recombination.

FIG 6

Relationship between SGI1 and variants of the SGI1-HKL group via the proposed progenitor SGI1-LK0. Steps leading to the formation of SGI1-LK0, the putative progenitor of the SGI1-HKL group, and then to new forms of the class 1 integron in the SGI1-HKL group are shown as arrows, with a summary of the events needed listed adjacent. The order of the steps is arbitrary. Details of the generation of the variants are shown in Fig. 1 to 5.