scholarly journals Microevolution within ST11 group Clostridioides difficile isolates through mobile genetic elements based on complete genome sequencing

BMC Genomics ◽  
2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Yuan Wu ◽  
Lin Yang ◽  
Wen-Ge Li ◽  
Wen Zhu Zhang ◽  
Zheng Jie Liu ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Resistance Genes ◽  
Point Mutations ◽  
Evolutionary Process ◽  
Mobile Genetic Elements ◽  
Genetic Elements ◽  
Clostridioides Difficile ◽  
Hospitalized Elderly ◽  
Great Heterogeneity ◽  
High Level

Abstract Background Clade 5 Clostridioides difficile diverges significantly from the other clades and is therefore, attracting increasing attention due its great heterogeneity. In this study, we used third-generation sequencing techniques to sequence the complete whole genomes of three ST11 C. difficile isolates, RT078 and another two new ribotypes (RTs), obtained from three independent hospitalized elderly patients undergoing antibiotics treatment. Mobile genetic elements (MGEs), antibiotic-resistance, drug resistance genes, and virulent-related genes were analyzed and compared within these three isolates. Results Isolates 10,010 and 12,038 carried a distinct deletion in tcdA compared with isolate 21,062. Furthermore, all three isolates had identical deletions and point-mutations in tcdC, which was once thought to be a unique characteristic of RT078. Isolate 21,062 (RT078) had a unique plasmid, different numbers of transposons and genetic organization, and harboring special CRISPR spacers. All three isolates retained high-level sensitivity to 11 drugs and isolate 21,062 (RT078) carried distinct drug-resistance genes and loss of numerous flagellum-related genes. Conclusions We concluded that capillary electrophoresis based PCR-ribotyping is important for confirming RT078. Furthermore, RT078 isolates displayed specific MGEs, indicating an independent evolutionary process. In the further study, we could testify these findings with more RT078 isolates of divergent origins.

scholarly journals Clostridioides difficile as a Dynamic Vehicle for the Dissemination of Antimicrobial-Resistance Determinants: Review and In Silico Analysis

2021 ◽  
Vol 9 (7) ◽  
pp. 1383
Author(s):  
Philip Kartalidis ◽  
Anargyros Skoulakis ◽  
Katerina Tsilipounidaki ◽  
Zoi Florou ◽  
Εfthymia Petinaki ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
Resistance Genes ◽  
In Silico ◽  
In Silico Analysis ◽  
Mobile Genetic Elements ◽  
Genetic Elements ◽  
Clostridioides Difficile ◽  
Antimicrobial Resistance Genes ◽  
Silico Analysis

The present paper is divided into two parts. The first part focuses on the role of Clostridioides difficile in the accumulation of genes associated with antimicrobial resistance and then the transmission of them to other pathogenic bacteria occupying the same human intestinal niche. The second part describes an in silico analysis of the genomes of C. difficile available in GenBank, with regard to the presence of mobile genetic elements and antimicrobial resistance genes. The diversity of the C. difficile genome is discussed, and the current status of resistance of the organisms to various antimicrobial agents is reviewed. The role of transposons associated with antimicrobial resistance is appraised; the importance of plasmids associated with antimicrobial resistance is discussed, and the significance of bacteriophages as a potential shuttle for antimicrobial resistance genes is presented. In the in silico study, 1101 C. difficile genomes were found to harbor mobile genetic elements; Tn6009, Tn6105, CTn7 and Tn6192, Tn6194 and IS256 were the ones more frequently identified. The genes most commonly harbored therein were: ermB, blaCDD, vanT, vanR, vanG and vanS. Tn6194 was likely associated with resistance to erythromycin, Tn6192 and CTn7 with resistance to the β-lactams and vancomycin, IS256 with resistance to aminoglycoside and Tn6105 to vancomycin.

scholarly journals Independent Microevolution Mediated by Mobile Genetic Elements of IndividualClostridium difficileIsolates from Clade 4 Revealed by Whole-Genome Sequencing

mSystems ◽  
2019 ◽  
Vol 4 (2) ◽  
Author(s):  
Yuan Wu ◽  
Chen Liu ◽  
Wen-Ge Li ◽  
Jun-Li Xu ◽  
Wen-Zhu Zhang ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Clostridium Difficile ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Mobile Genetic Elements ◽  
High Rate ◽  
Whole Genome ◽  
Content Type ◽  
Genetic Elements ◽  
Sequence Types

ABSTRACTHorizontal gene transfer of mobile genetic elements (MGEs) accounts for the mosaic genome ofClostridium difficile, leading to acquisition of new phenotypes, including drug resistance and reconstruction of the genomes. MGEs were analyzed according to the whole-genome sequences of 37C. difficileisolates with a variety of sequence types (STs) within clade 4 from China. Great diversity was found in each transposon even within isolates with the same ST. Two novel transposons were identified in isolates ZR9 and ZR18, of which approximately one third to half of the genes showed heterogenous origins compared with the usual intestinal bacterial genes. Most importantly,catD, known to be harbored by Tn4453a/b, was replaced byaac(6′) aph(2′′)in isolates 2, 7, and 28. This phenomenon illustrated the frequent occurrence of gene exchanges betweenC. difficileand other enterobacteria with individual heterogeneity. Numerous prophages and CRISPR arrays were identified inC. difficileisolates of clade 4. Approximately 20% of spacers were located in prophage-carried CRISPR arrays, providing a new method for typing and tracing the origins of closely related isolates, as well as in-depth studies of the mechanism underlying genome remodeling. The rates of drug resistance were obviously higher than those reported previously around the world, although all isolates retained high sensitivity to vancomycin and metronidazole. The increasing number ofC. difficileisolates resistant to all antibiotics tested here suggests the ease with which resistance is acquiredin vivo. This study gives insights into the genetic mechanism of microevolution within clade 4.IMPORTANCEMobile genetic elements play a key role in the continuing evolution ofClostridium difficile, resulting in the emergence of new phenotypes for individual isolates. On the basis of whole-genome sequencing analysis, we comprehensively explored transposons, CRISPR, prophage, and genetic sites for drug resistance within clade 4C. difficileisolates with different sequence types. Great diversity in MGEs and a high rate of multidrug resistance were found within this clade, including new transposons, Tn4453a/bwithaac(6′) aph(2′′)instead ofcatD, and a relatively high rate of prophage-carried CRISPR arrays. These findings provide important new insights into the mechanism of genome remodeling within clade 4 and offer a new method for typing and tracing the origins of closely related isolates.

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