Variant Salmonella Genomic Island 1 Antibiotic Resistance Gene Cluster Containing a Novel 3′- N -Aminoglycoside Acetyltransferase Gene Cassette, aac (3)- Id , in Salmonella enterica Serovar Newport

Abstract

A chromosomal genomic island called Salmonella genomic island 1 (SGI1) has been initially described in epidemic multidrugresistant Salmonella enterica serovar Typhimurium phage type DT104 strains (serovar Typhimurium DT104) (4). SGI1 contains an antibiotic resistance gene cluster conferring the common multidrug resistance profile ApCmFfSmSpSuTc (i.e., ampicillin [Ap] (1, 2, 4-7, 12, 13, 23, 24, 30, 31). Multidrug-resistant serovar Typhimurium DT104 emerged during the 1980s as a global health problem because of its involvement in diseases in animals and humans (7,12,13,23,24,30,31).The 43-kb SGI1 is located between the thdF and int2 genes of the chromosome of serovar Typhimurium. The int2 gene is part of a retron sequence, which has been reported to date only in serovar Typhimurium strains (4, 5). In other S. enterica serovars, SGI1 is located between the thdF and yidY genes (3, 4, 9-11, 17, 18). The antibiotic resistance gene cluster is located near the 3Ј end of SGI1 and constitutes a complex class 1 integron that belongs to the In4 group (3). The In4 group has a 3Ј conserved segment (3Ј-CS) that includes a copy of IS6100 but no transposition genes, and most members are bound by 25-bp inverted repeats IRi and IRt (20,21). The antibiotic resistance gene cluster of SGI1 is indeed bound by IRi and IRt and thus can be considered a complex In4-type integron (3). Further, the multidrug resistance region is surrounded by 5-bp direct repeats, strongly suggesting it was integrated by a transposition event (3,20,21). Interestingly, in SGI1 there is a duplication of a part of the 5Ј conserved segment (5Ј-CS) of the integron that leads to a second attI1 site, followed by a gene cassette. At the first attI1 site, the cassette carries the aadA2 gene, which confers resistance to Sm and Sp, and a 3Ј-CS with a truncated sul1 (sul1⌬) gene. At the second attI1 site, the cassette contains the ␤-lactamase gene pse-1 conferring resistance to Ap and a 3Ј-CS with a complete sul1 gene conferring resistance to Su. Flanked by the two cassettes are the floR gene, which confers cross-resistance to Cm and Ff, and the Tc resistance genes tetR and tet(G) (1,2,4,6).Variant SGI1 antibiotic resistance gene clusters have recently been described in the serovars Typhimurium DT104, Agona, and Albany. SGI1 variants were accordingly classified in SGI1-A to SGI1-G (3, 9, 11). These clusters of antibiotic resistance genes were likely generated, according to sequence analysis, after chromosomal recombinational events or by antibiotic resistance gene cassette replacement at one of the attI1 sites. In variants SGI1-A, -D, and -G, the 3Ј-CS, designated 3Ј-CS1, is followed by the orf513/dfrA10 region originally described in In6 and In7 (19,29). Following the orf513/dfrA10

Emergence of Salmonella epidemics: The problems related to Salmonella enterica serotyp Enteritidis and multiple antibiotic resistance in other major serotypes

“…Horizontal transfer of SGI1 has been supported by its discovery in other S. enterica serotypes, namely S. Agona, S. Paratyphi B, S. Albany, and S. Newport [22,43,44,97]. In these serotypes, SGI1 has the same chromosomal location as in S. Typhimurium DT104, i.e.…”

“…In such a case, it looks more like an antibiotic resistance gene cluster and to date SGI1 variants have been identified carrying up to six antibiotic resistance genes, conferring a multiple-antibiotic resistance profile to antibiotic families of clinical importance such as β-lactams, aminoglycosides, phenicols, sulfonamides, tetracyclines, and trimethoprim [21,22]. In addition, the structures carrying these various antibiotic resistance genes may undergo recombinational, gene replacement and gene capture events, which can lead to a wide variety of antibiotic resistance gene clusters [22,43,44].…”

“…The variant SGI1-H from S. Newport strains isolated from French patients with gastroenteritis represented the second example where gene cassette replacement took place in one of its attI1 sites [44]. In these strains, the Sm/Sp resistance gene cassette aadA2 inserted at the first attI1 site was replaced by two other aminoglycoside resistance gene cassettes.…”

SGI1-K, a Variant of the SGI1 Genomic Island Carrying a Mercury Resistance Region, in Salmonella enterica Serovar Kentucky

“…A number of variants of SGI1 containing different sets of resistance genes have also been identified (3,9,(12)(13)(14)18). These variants, SGI1-A to SGI1-J, appear to have gained, lost, or exchanged resistance genes by gaining and/or losing various segments of DNA, mostly as a result of events that could have occurred by homologous recombination (see references 3, 13, and 18).…”

“…Some variants have lost the central region of In104 and include only one attI1 site containing gene cassettes. Others include gene cassettes that differ from those in SGI1, such as the dfrA1-orfC or the aacCA5-aadA7 pairs (13,14,18), or have a deletion encompassing an attI site (18). Further variants (3,18) have gained an additional dfrA10 trimethoprim resistance gene associated with the potential insertion sequence known as CR1, which draws a variety of resistance genes into the complex class 1 integrons that contain it (28).…”