Dissemination of IncI2 Plasmids That Harbor the bla _CTX-M Element among Clinical Salmonella Isolates

Abstract

cThe extended-spectrum-␤-lactamase (ESBL) determinant CTX-M-55 is increasingly prevalent in Escherichia coli but remains extremely rare in Salmonella. This study reports the isolation of a plasmid harboring the bla CTX-M-55 element in a clinical Salmonella enterica serotype Typhimurium strain resistant to multiple antibiotics. This plasmid is genetically identical to several known IncI2-type elements harbored by E. coli strains recovered from animals. This finding indicates that IncI2 plasmids harboring the bla CTX-M genes may undergo cross-species migration among potential bacterial pathogens, with E. coli as the major source of such elements. Salmonellosis is a serious public health problem worldwide (1-3). Ceftriaxone and ciprofloxacin are the choice of treatment for invasive Salmonella infections (4). Resistance to ceftriaxone or other extended-spectrum ␤-lactams (ESBL) is usually due to the CTX-M group ESBLs in Salmonella spp., with CTX-M-9, CTX-M-14, and CTX-M-15 the most commonly reported in China and several other regions of the world (5-7). Genes encoding CTX-Mtype ESBLs are usually located in transmissible plasmids, which tend to disseminate among members of the family of Enterobacteriaceae (8). Various studies previously reported the presence of IncI1 plasmids that carried the bla CTX-M-14 element and other bla CTX-M variants in Salmonella spp. (9-11). In addition, other plasmid types, such as IncF, FIIA, F1B, HI2, Y, and B/O, have also been reported to be associated with bla CTX-M-14 and other bla CTX-M elements in Salmonella enterica serotype Typhimurium (12).In addition to CTX-M-14 and CTX-M-15, CTX-M-55 was increasingly reported in various countries in recent years, particularly among Escherichia coli isolates of zoonotic origin (13-17). However, it has not been found in Salmonella isolates. This element is frequently associated with the transposase ISEcp1 and is increasingly found in the IncI2 plasmids (18). Recently, several IncI2 plasmids, which harbored the bla CTX-M-55 element, were sequenced (19,20). On the basis of the genetic similarity between elements recovered from different bacterial species and a major discrepancy in the prevalence rate of different bla CTX-M elements in E. coli and Salmonella isolates, we speculate that bla CTX-M -borne plasmids might originate from E. coli and possess the ability to disseminate to Salmonella and other bacterial species.In this study, we identified a bla CTX-M-55 -positive Salmonella Typhimurium strain named STH21 that was isolated from a stool specimen from a patient in 2008 in Henan Province, People's Republic of China. Antimicrobial susceptibility tests performed according to the CLSI guideline revealed that STH21 was resistant to various antimicrobial drugs, including ampicillin, ceftriaxone, cefotaxime, amikacin, ciprofloxacin, and azithromycin (Table 1) (21). A bla CTX-M-55 -bearing plasmid recovered from this strain and the corresponding cefotaxime resistance phenotype was transferred to E. coli J53 by conjugation (22). S1-pulsed-field gel ele...

Emergence and Diversity of Salmonella enterica Serovar Indiana Isolates with Concurrent Resistance to Ciprofloxacin and Cefotaxime from Patients and Food-Producing Animals in China

“…Interestingly, bla CTX-M is often located on conjugative plasmids. It has been reported that ciprofloxacin-resistant S. enterica serovar Kentucky ST198-X1 acquired the genes conferring resistance to extended-spectrum cephalosporins only recently (28), and certain genotypes, such as bla CTX-M-55 , are borne on plasmids that may have originated from E. coli possessing the ability to disseminate to Salmonella and other bacterial species (34). Conjugative systems in Gram-negative bacteria support transfer of mobile genetic elements between different genera, and in this study five transconjugants (8.25%; 5/61) were obtained.…”

The Continuing Plague of Extended-spectrum β-lactamase–producing Enterobacteriaceae Infections

“…27,72 Additional contributing factors to the epidemic of ESBL infections in the community in general, and of bla CTX-M -producing E coli infections in particular, may be related to the agriculture and food industries. [106][107][108][109] Unfortunately, misuse of antibiotics in these industries is common and not tightly regulated. [110][111][112] Many community outbreaks of bla CTX-M -producing E coli infections, originating from the agriculture and food industries, were reported in the past decade.…”

“…[110][111][112] Many community outbreaks of bla CTX-M -producing E coli infections, originating from the agriculture and food industries, were reported in the past decade. 85,[106][107][108][109][113][114][115][116][117][118][119][120][121] One of the largest ever reported was an outbreak in 2011 of a bla CTX-M -producing E coli strain that was associated with hemolytic uremic syndrome and several deaths among previously healthy and young individuals, mainly from Germany and France. 122,123 It was suggested that the outbreak resulted from contaminated food products that were distributed in various European countries.…”

Whole-Genome Sequencing Identifies In Vivo Acquisition of a bla CTX-M-27 -Carrying IncFII Transmissible Plasmid as the Cause of Ceftriaxone Treatment Failure for an Invasive Salmonella enterica Serovar Typhimurium Infection

“…Twenty-five years later, with the widespread use of whole-genome sequencing, coverage of this group of plasmids has exploded through recognition of their role in spread of antibiotic resistance, particularly ESBL ␤-lactamases-with over 200 PubMed articles relating to IncI1 plasmids in the last decade; IncI2 plasmids have only recently been discovered as vectors for ESBL and other resistance determinants (99), with more than half of relevant Pubmed articles published since 2013. Both sets of plasmids were historically associated with E. coli but are increasingly found in NTS isolates (80,100). Alarmingly, ESBL-encoding IncI2 plasmids are now spreading the colistin resistance determinant mcr-1 in China (101) and Europe (102).…”

“…In the United States, most third-generation cephalosporin resistance among human Salmonella isolates has historically been due to a plasmidmediated bla CMY-2 (AmpC-type) ␤-lactamases (14,78,79), and while NTS with ESBL determinants (including bla CTX-M ) are increasingly common in other parts of the world (19,(80)(81)(82), they still remain rare in the United States (83). bla CTX-M determinants in NTS infections are now being reported in the United States (84) and have increased significantly in veterinary and food isolates in the rest of the world in recent years (85)(86)(87).…”