Sequential Isolation in a Patient of Raoultella planticola and Escherichia coli Bearing a Novel ISCR1 Element Carrying blaNDM-1

c Acquisition of bla NDM-1 in bacterial species, such as Proteus mirabilis that is intrinsically resistant to tetracycline, tigecycline and colistin, will make clinical treatment extremely difficult. Here, we characterized an NDM-1-producing clinical isolate of P. mirabilis (PM58) that displayed an extensively drug-resistant (XDR) phenotype, susceptible only to aztreonam. Molecular analysis revealed that PM58 harbored both a conjugative NDM-1 plasmid and a novel Salmonella genomic island 1 variant on chromosome.G lobal dissemination of New Delhi metallo-␤-lactamase 1 (NDM-1), an Ambler class B metallo-␤-lactamase (MBL) able to hydrolyze all ␤-lactams except monobactams, in Gramnegative bacteria represents a great threat for public health (1). Transmission of bla NDM-1 is of especial concern with bacterial species of intrinsic antibiotic resistance, such as Proteus mirabilis that is intrinsically resistant to tetracycline, tigecycline and colistin, which will make clinical treatment extremely difficult.Salmonella genomic island 1 (SGI1), consisting of a conserved backbone structure and a multidrug resistance (MDR) region, is integrated into the chromosome specifically at the last 18 bp of the 3=-end of the thdF gene and was initially reported in Salmonella enterica serovar Typhimurium DT104 (2). To date, multiple variants of SGI1 have been discovered, and they are classified from SGI1-A to SGI1-Y, corresponding to various structures of the MDR region. Since several novel variants of SGI1, such as SGI1-L and SGI1-U to SGI1-Y, have been identified in P. mirabilis, this species is considered an acceptor of SGI independent of Salmonella spp. (3-5). Recently, the bla NDM-1 gene was reportedly integrated into a novel SGI1 variant, named PGI1 (Proteus genomic island 1), in a P. mirabilis clinical isolate (6). However, the bla NDM-1 carrying PGI1 was nontransferable in the presence of helper plasmid pR55, and this PGI1-harboring isolate remained susceptible to multiple antibiotics, including meropenem, ertapenem, gentamicin, and fosfomycin (6). Here, we describe a clinical extensively drug resistant (XDR) P. mirabilis isolate that harbors both a conjugative NDM-1 plasmid and a novel SGI1 variant on chromosome.A 3-year-old girl was admitted to the emergency department of The First Affiliated Hospital of Zhengzhou University on August 10, 2013, with a diagnosis of spinal cord injury (SCI) caused by a knife injury. After the surgery operation on August 11, intravenous cefathiamidine was given empirically (1 g administered 2 times/day) for 1 week to prevent bacterial infections. After receiving treatment, the patient was in a stable condition and was transferred to the rehabilitation department for restorative treatment. Unfortunately, the patient developed symptoms of frequent and urgent micturition and urodynia on December 10, 2013, and was treated with gentamicin bladder irrigations via catheter (20 mg administered 2 times/day). On December 15, an XDR P. mirabilis isolate named PM58 in this study was obtained from the uri...

supporting

confidence: 79%

mentioning

confidence: 99%

Emergence of Extensively Drug-Resistant Proteus mirabilis Harboring a Conjugative NDM-1 Plasmid and a Novel Salmonella Genomic Island 1 Variant, SGI1-Z

Qin

Zhang

et al. 2015

“…ISCR1 has generally been found associated with class 1 integrons, after position 1,313 of the 3=-CS, suggesting integration of circular molecules by recombination in either the 3=-CS or an existing ISCR1 (38). ISCR1 has previously been suggested to be associated with movement of bla NDM (39) and was recently shown to be responsible for mobilizing a region containing bla NDM and part of the 3=-CS, but without the bla DHA ⌬-ampR region, between plasmids (20).…”

Section: Resultsmentioning

confidence: 99%

“…1A). In plasmids from the Enterobacteriaceae, bla NDM genes are generally found in this immediate genetic context, with at least a fragment of ISAba125 containing the Ϫ35 promoter region present upstream, within different length fragments matching Acinetobacter plasmids and associated with different mobile elements (3,(16)(17)(18)(19)(20)(21).…”

mentioning

confidence: 99%

Mechanisms Involved in Acquisition of bla _NDM Genes by IncA/C ₂ and IncFII _Y Plasmids

Wailan

Sidjabat

Yam

et al. 2016

g bla NDM genes confer carbapenem resistance and have been identified on transferable plasmids belonging to different incompatibility (Inc) groups. Here we present the complete sequences of four plasmids carrying a bla NDM gene, pKP1-NDM-1, pEC2-NDM-3, pECL3-NDM-1, and pEC4-NDM-6, from four clinical samples originating from four different patients. Different plasmids carry segments that align to different parts of the bla NDM region found on Acinetobacter plasmids. pKP1-NDM-1 and pEC2-NDM-3, from Klebsiella pneumoniae and Escherichia coli, respectively, were identified as type 1 IncA/C 2 plasmids with almost identical backbones. Different regions carrying bla NDM are inserted in different locations in the antibiotic resistance island known as ARI-A, and ISCR1 may have been involved in the acquisition of bla NDM-3 by pEC2-NDM-3. pECL3-NDM-1 and pEC4-NDM-6, from Enterobacter cloacae and E. coli, respectively, have similar IncFII Y backbones, but different regions carrying bla NDM are found in different locations. Tn3-derived inverted-repeat transposable elements (TIME) appear to have been involved in the acquisition of bla NDM-6 by pEC4-NDM-6 and the rmtC 16S rRNA methylase gene by IncFII Y plasmids. Characterization of these plasmids further demonstrates that even very closely related plasmids may have acquired bla NDM genes by different mechanisms. These findings also illustrate the complex relationships between antimicrobial resistance genes, transposable elements, and plasmids and provide insights into the possible routes for transmission of bla NDM genes among species of the Enterobacteriaceae family.

“…Partridge and Hall confirmed that a small circular molecule containing ISCR1-dfrA10-sul1 could be transposed into a plasmid within the 3=-conserved sequence (CS) of a cloned class 1 integron in vitro (26). Li et al first identified the circular molecule with ISCR1-bla NDM-1 -3=-CS in a clinical E. coli strain by Southern hybridization (27), and Li et al and Wu et al reported the existence of ISCR1-bla PER-1 -3=-CS in V. cholerae and V. parahaemolyticus using PCR with inverse primers (18,20). In this study, a free circular molecule bearing the ISCR1-bla PER structure was identified in all ISCR1-related isolates by PCR with a pair of inverse primers ( Table 2).…”

Section: Fig 1 Pulsed-field Gel Electrophoresis (Pfge) Profiles Of Prmentioning

confidence: 99%

Molecular Epidemiology and Genetic Characteristics of Various bla _PER Genes in Shanghai, China

Xie

Zhang

et al. 2016

We describe the genetic characteristics and possible transmission mechanism of bla PER in 25 clinical Gram-negative bacilli in Shanghai. bla PER , including bla PER-1 , bla PER-3 , and bla PER-4 , was located chromosomally or in different plasmids. Tn1213 harboring bla PER-1 was first identified in two Proteus mirabilis isolates in China. The other bla PER variants were preceded by an ISCR1 element inside the complex class 1 integron associated with IS26, Tn21, Tn1696, and a miniature inverted-repeat transposable element.