Dataset Information

First report of bla_OXA-181-carrying IncX3 plasmids in multidrug-resistant Enterobacter hormaechei and Serratia nevei recovered from canine and feline opportunistic infections.

ABSTRACT: Whole-genome sequence analysis of six Enterobacter hormaechei and two Serratia nevei strains, using a hybrid assembly of Illumina and Oxford Nanopore Technologies sequencing, revealed the presence of the epidemic bla_OXA-181-carrying IncX3 plasmids co-harboring qnrS1 and ∆ere(A) genes, as well as multiple multidrug resistance (MDR) plasmids disseminating in all strains, originated from dogs and cats in Thailand. The subspecies and sequence types (ST) of the E. hormaechei strains recovered from canine and feline opportunistic infections included E. hormaechei subsp. xiangfangensis ST171 (n = 3), ST121 (n = 1), and ST182 (n = 1), as well as E. hormaechei subsp. steigerwaltii ST65 (n = 1). Five of the six E. hormaechei strains harbored an identical 51,479-bp bla_OXA-181-carrying IncX3 plasmid. However, the bla_OXA-181 plasmid (pCUVET22-969.1) of the E. hormaechei strain CUVET22-969 presented a variation due to the insertion of ISKpn74 and ISSbo1 into the virB region. Additionally, the bla_OXA-181 plasmids of S. nevei strains were nearly identical to the others at the nucleotide level, with ISEcl1 inserted upstream of the qnrS1 gene. The E. hormaechei and S. nevei lineages from canine and feline origins might acquire the epidemic bla_OXA-181-carrying IncX3 and MDR plasmids, which are shared among Enterobacterales, contributing to the development of resistance. These findings suggest the spillover of significant OXA-181-encoding plasmids to these bacteria, causing severe opportunistic infections in dogs and cats in Thailand. Surveillance and effective hygienic practice, especially in hospitalized animals and veterinary hospitals, should be urgently implemented to prevent the spread of these plasmids in healthcare settings and communities.

Importance

bla_OXA-181 is a significant carbapenemase-encoding gene, usually associated with an epidemic IncX3 plasmid found in Enterobacterales worldwide. In this article, we revealed six carbapenemase-producing (CP) Enterobacter hormaechei and two CP Serratia nevei strains harboring bla_OXA-181-carrying IncX3 and multidrug resistance plasmids recovered from dogs and cats in Thailand. The carriage of these plasmids can promote extensively drug-resistant properties, limiting antimicrobial treatment options in veterinary medicine. Since E. hormaechei and S. nevei harboring bla_OXA-181-carrying IncX3 plasmids have not been previously reported in dogs and cats, our findings provide the first evidence of dissemination of the epidemic plasmids in these bacterial species isolated from animal origins. Pets in communities can serve as reservoirs of significant antimicrobial resistance determinants. This situation places a burden on antimicrobial treatment in small animal practice and poses a public health threat.

SUBMITTER: Leelapsawas C

PROVIDER: S-EPMC10913469 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature

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First report of blaOXA-181-carrying IncX3 plasmids in multidrug-resistant Enterobacter hormaechei and Serratia nevei recovered from canine and feline opportunistic infections.

Leelapsawas Chavin C Sroithongkham Parinya P Payungporn Sunchai S Nimsamer Pattaraporn P Yindee Jitrapa J Collaud Alexandra A Perreten Vincent V Chanchaithong Pattrarat P

Microbiology spectrum 20240206 3

Whole-genome sequence analysis of six Enterobacter hormaechei and two Serratia nevei strains, using a hybrid assembly of Illumina and Oxford Nanopore Technologies sequencing, revealed the presence of the epidemic blaOXA-181-carrying IncX3 plasmids co-harboring qnrS1 and ∆ere(A) genes, as well as multiple multidrug resistance (MDR) plasmids disseminating in all strains, originated from dogs and cats in Thailand. The subspecies and sequence types (ST) ...[more]

PMID: 38319115

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Project description:Carbapenem-resistant Enterobacterales poses a global urgent antibiotic resistance threat because of its ability to transfer carbapenemase genes to other bacteria via horizontal gene transfer mediated by mobile genetic elements such as plasmids. Oxacillinase-181 (OXA-181) is one of the most common OXA-48-like carbapenemases, and OXA-181-producing Enterobacterales has been reported in many countries worldwide. However, systematic research concerning the overall picture of plasmids harboring bla OXA-181 in Enterobacterales is currently scarce. In this study, we aimed to determine the phylogeny and evolution of bla OXA-181-positive (gene encoding OXA-181) plasmids. To characterize the plasmids harboring bla OXA-181 in Enterobacterales, we identified 81 bla OXA-181-positive plasmids from 35,150 bacterial plasmids downloaded from the NCBI RefSeq database. Our results indicated that diverse plasmid types harbored bla OXA-181 but was predominantly carried by IncX3-type plasmids. We systematically compared the host strains, plasmid types, conjugative transfer regions, and genetic contexts of bla OXA-181 among the 66 bla OXA-181-positive IncX3 plasmids. We found that IncX3 plasmids harboring bla OXA-181 were mostly ColKP3-IncX3 hybrid plasmids with a length of 51 kb each and were mainly distributed in Escherichia coli and Klebsiella pneumoniae. Most of the IncX3 plasmids harboring bla OXA-181 were human origin. Almost all the bla OXA-181-positive IncX3 plasmids were found to carry genes coding for relaxases of the MOBP family and VirB-like type IV secretion system (T4SS) gene clusters, and all the 66 IncX3 plasmids were found to carry the genes encoding type IV coupling proteins (T4CPs) of the VirD4/TraG subfamily. Most IncX3 plasmids harbored both bla OXA-181 and qnrS1 in their genomes, and the two antibiotic resistance genes were found to a composite transposon bracketed by two copies of insertion sequence IS26 in the same orientation. Our findings provide important insights into the phylogeny and evolution of bla OXA-181-positive IncX3 plasmids and further address their role in acquiring and spreading bla OXA-181 genes in Enterobacterales.

Project description:IncX3 and IncL plasmids have been named as catalysts advancing dissemination of blaOXA-181 and blaOXA-48 genes. However, their impact on the performance of host cells is vastly understudied. Genetic characteristics of blaOXA-48- and blaOXA-181-containing Klebsiella pneumoniae (EFN299), Klebsiella quasipneumoniae (EFN262), and Enterobacter cloacae (EFN743) isolated from clinical samples in a Ghanaian hospital were investigated by whole-genome sequencing. Transfer of plasmids by conjugation and electroporation, plasmid stability, fitness cost, and genetic context of blaOXA-48, blaOXA-181, and blaDHA-1 were assessed. blaOXA-181 was carried on two IncX3 plasmids, an intact 51.5-kb IncX3 plasmid (p262-OXA-181) and a 45.3-kb IncX3 plasmid (p743-OXA-181) without replication protein sequence. The fluoroquinolone-resistant gene qnrS1 region was also excised, and unlike in p262-OXA-181, the blaOXA-181 drug-resistant region was not found on a composite transposon. blaOXA-48 was carried on a 74.6-kb conjugative IncL plasmid with unknown ~10.9-kb sequence insertion. This IncL plasmid proved to be highly transferable, with a conjugation efficiency of 1.8 × 10-2. blaDHA-1 was present on an untypeable 22.2 kb genetic structure. Plasmid stability test revealed plasmid loss rate between 4.3% and 12.4%. The results also demonstrated that carriage of IncX3-blaOXA-181 or IncL-blaOXA-48 plasmids was not associated with any fitness defect, but rather an enhanced competitive ability of host cells. This study underscores the significant contribution of IncX3 and IncL plasmids in the dissemination of resistance genes and their efficient transfer calls for regular monitoring to control the expansion of resistant strains. IMPORTANCE The growing rate of antibiotic resistance is an important global health threat. This threat is exacerbated by the lack of safe and potent alternatives to carbapenems in addition to the slow developmental process of newer and effective antibiotics. Infections by carbapenem-resistant Gram-negative bacteria are becoming almost untreatable, leading to poor clinical outcomes and high mortality rates. OXA-48-like carbapenemases are one of the most widespread carbapenemases accounting for resistance among Enterobacteriaecae. We characterized OXA-48- and OXA-181-producing Enterobacteriaecae to gain insights into the genetic basis and mechanism of resistance to carbapenems. Findings from the study showed that the genes encoding these enzymes were carried on highly transmissible plasmids, one of which had sequences absent in other similar plasmids. This implies that mobile genetic elements are important players in the dissemination of resistance genes. Further characterization of this plasmid is warranted to determine the role of this sequence in the spread of resistance genes.

Project description:Dissemination of blaNDM, which is carried on the IncX3 plasmid, among Enterobacterales has been reported worldwide. In particular, blaNDM-5-carrying IncX3 plasmids can spread among several hosts, facilitating their dissemination. Other variants, such as blaNDM-17-, blaNDM-19-, blaNDM-20-, blaNDM-21-, and blaNDM-33-carrying IncX3 plasmids, have also been reported. Here, we characterized, using whole-genome sequencing (WGS), a blaNDM-16b-carrying IncX3 plasmid harbored by Escherichia coli strain TA8571, which was isolated from a urine specimen of a hospital inpatient in Tokyo, Japan. The blaNDM-16b differed in sequence from blaNDM-5 (C > T at site 698, resulting in an Ala233Val substitution). This blaNDM-16b-carrying IncX3 plasmid (pTMTA8571-1) is 46,161 bp in length and transferred via conjugation. Transconjugants showed high resistance to β-lactam antimicrobials (except for aztreonam). Because pTMTA8571-1, which carries the Tn125-related region containing blaNDM and conjugative transfer genes, was similar to the previously reported IncX3 plasmids, we performed phylogenetic analysis based on the sequence of 34 shared genes in 142 blaNDM-carrying IncX3 plasmids (22,846/46,923 bp). Comparative analysis of the shared genes revealed short branches on the phylogenetic tree (average of 1.08 nucleotide substitutions per shared genes), but each blaNDM variant was divided into separate groups, and the structure of the tree correlated with the flowchart of blaNDM nucleotide substitutions. The blaNDM-carrying IncX3 plasmids may thereby have evolved from the same ancestral plasmid with subsequent mutation of the blaNDM. Therefore, pTMTA8571-1 likely emerged from a blaNDM-5-carrying IncX3 plasmid. This study suggested that the spread of blaNDM-carrying IncX3 plasmids may be a hotbed for the emergence of novel variants of blaNDM. IMPORTANCE blaNDM-carrying IncX3 plasmids have been reported worldwide. Harbored blaNDM variants were mainly blaNDM-5, but there were also rare variants like blaNDM-17, blaNDM-19, blaNDM-20, blaNDM-21, and blaNDM-33, including blaNDM-16b detected in this study. For these plasmids, previous reports analyzed whole genomes or parts of sequences among a small number of samples, whereas, in this study, we performed an analysis of 142 blaNDM-carrying IncX3 plasmids detected around the world. The results showed that regardless of the blaNDM variants, blaNDM-carrying IncX3 plasmids harbored highly similar shared genes. Because these plasmids already spread worldwide may be a hotbed for the emergence of rare or novel variants of blaNDM, increased attention should be paid to blaNDM-carrying IncX3 plasmids in the future.

Project description:BackgroundCarbapenem-Resistant Enterobacterales (CRE) has been categorized as pathogens of critical priority by World Health organization (WHO) as they pose significant threat to global public health. Carbapenemase production considered as the principal resistance mechanism against carbapenems and with the recent surge and expansion of carbapenemases and its variants among clinically significant bacteria in India, the present study reports expansion blaOXA-78 and blaOXA-58 of in CRE of clinical origin.MethodsBacterial isolates were collected from a tertiary referral hospital and identified through VITEK® 2 Compact automated System (Biomerieux, France). Rapidec® Carba NP (Biomerieux, France) was used to investigate carbapenemase production followed by antibiotic susceptibility testing through Kirby-Bauer Disc Diffusion method and agar dilution method. Class D carbapenemase genes were targeted through PCR assay followed by investigation of horizontal transmission of blaOXA-58 and blaOXA-78. Whole genome sequencing was carried out using Illumina platform to investigate the genetic context of blaOXA-58 and blaOXA-78 genes and further characterization of the CRE isolates.ResultsThe carbapenem-resistant Escherichia coli (BJD_EC456) and Serratia marcescens (BJD_SM81) received during the study from the tertiary referral hospital were isolated from sputum and blood samples respectively. PCR assay followed by whole genome sequencing revealed that the isolates co-harbor blaOXA-58 and blaOXA-78, a variant of blaOXA-51. Horizontal transfer of blaOXA-58 and blaOXA-78 genes were unsuccessful as these genes were located on the chromosome of the study isolates. Transposon Tn6080 was linked to blaOXA-78 in the upstream region while the insertion sequences ISAba26 and ISCfr1 were identified in the upstream and downstream region of blaOXA-58 gene respectively. In addition, both the isolates were co-harboring multiple antibiotic resistance genes conferring clinical resistance towards beta-lactams, aminoglycosides, fluroquinolones, sulphonamides, tetracyclines. BJD_EC180 belonged to ST2437 while BJD_SM81 was of an unknown sequence type. The nucleotide sequences of blaOXA-78 (OQ533021) and blaOXA-58 (OQ533022) have been deposited in GenBank.ConclusionsThe study provides a local epidemiological information regarding carbapenem resistance aided by transposon and insertion sequences associated blaOXA-78 and blaOXA-58 genes associated and warrants continuous monitoring to prevent their further dissemination into carbapenem non-susceptible strains thereby contributing to carbapenem resistance burden which is currently a global concern.

Dataset Information

First report of bla_OXA-181-carrying IncX3 plasmids in multidrug-resistant Enterobacter hormaechei and Serratia nevei recovered from canine and feline opportunistic infections.

Importance

Publications

First report of <i>bla</i><sub>OXA-181</sub>-carrying IncX3 plasmids in multidrug-resistant <i>Enterobacter hormaechei</i> and <i>Serratia nevei</i> recovered from canine and feline opportunistic infections.

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