Independent Microevolution Mediated by Mobile Genetic Elements of Individual <named-content content-type="genus-species">Clostridium difficile</named-content> Isolates from Clade 4 Revealed by Whole-Genome Sequencing

ABSTRACT Horizontal gene transfer of mobile genetic elements (MGEs) accounts for the mosaic genome of Clostridium 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 37 C. diff...

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Autores principales:	Yuan Wu, Chen Liu, Wen-Ge Li, Jun-Li Xu, Wen-Zhu Zhang, Yi-Fei Dai, Jin-Xing Lu
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	Clostridium difficile antifungal resistance horizontal gene transfer microevolution mobile genetic elements Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/bfa9327832b84a55a104ed2b974da6e6
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spelling	oai:doaj.org-article:bfa9327832b84a55a104ed2b974da6e62021-12-02T18:15:44ZIndependent Microevolution Mediated by Mobile Genetic Elements of Individual <named-content content-type="genus-species">Clostridium difficile</named-content> Isolates from Clade 4 Revealed by Whole-Genome Sequencing10.1128/mSystems.00252-182379-5077https://doaj.org/article/bfa9327832b84a55a104ed2b974da6e62019-04-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSystems.00252-18https://doaj.org/toc/2379-5077ABSTRACT Horizontal gene transfer of mobile genetic elements (MGEs) accounts for the mosaic genome of Clostridium 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 37 C. difficile isolates 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 by aac(6′) aph(2′′) in isolates 2, 7, and 28. This phenomenon illustrated the frequent occurrence of gene exchanges between C. difficile and other enterobacteria with individual heterogeneity. Numerous prophages and CRISPR arrays were identified in C. difficile isolates 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 of C. difficile isolates resistant to all antibiotics tested here suggests the ease with which resistance is acquired in vivo. This study gives insights into the genetic mechanism of microevolution within clade 4. IMPORTANCE Mobile genetic elements play a key role in the continuing evolution of Clostridium 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 4 C. difficile isolates with different sequence types. Great diversity in MGEs and a high rate of multidrug resistance were found within this clade, including new transposons, Tn4453a/b with aac(6′) aph(2′′) instead of catD, 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.Yuan WuChen LiuWen-Ge LiJun-Li XuWen-Zhu ZhangYi-Fei DaiJin-Xing LuAmerican Society for MicrobiologyarticleClostridium difficileantifungal resistancehorizontal gene transfermicroevolutionmobile genetic elementsMicrobiologyQR1-502ENmSystems, Vol 4, Iss 2 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Clostridium difficile antifungal resistance horizontal gene transfer microevolution mobile genetic elements Microbiology QR1-502
spellingShingle	Clostridium difficile antifungal resistance horizontal gene transfer microevolution mobile genetic elements Microbiology QR1-502 Yuan Wu Chen Liu Wen-Ge Li Jun-Li Xu Wen-Zhu Zhang Yi-Fei Dai Jin-Xing Lu Independent Microevolution Mediated by Mobile Genetic Elements of Individual <named-content content-type="genus-species">Clostridium difficile</named-content> Isolates from Clade 4 Revealed by Whole-Genome Sequencing
description	ABSTRACT Horizontal gene transfer of mobile genetic elements (MGEs) accounts for the mosaic genome of Clostridium 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 37 C. difficile isolates 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 by aac(6′) aph(2′′) in isolates 2, 7, and 28. This phenomenon illustrated the frequent occurrence of gene exchanges between C. difficile and other enterobacteria with individual heterogeneity. Numerous prophages and CRISPR arrays were identified in C. difficile isolates 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 of C. difficile isolates resistant to all antibiotics tested here suggests the ease with which resistance is acquired in vivo. This study gives insights into the genetic mechanism of microevolution within clade 4. IMPORTANCE Mobile genetic elements play a key role in the continuing evolution of Clostridium 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 4 C. difficile isolates with different sequence types. Great diversity in MGEs and a high rate of multidrug resistance were found within this clade, including new transposons, Tn4453a/b with aac(6′) aph(2′′) instead of catD, 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.
format	article
author	Yuan Wu Chen Liu Wen-Ge Li Jun-Li Xu Wen-Zhu Zhang Yi-Fei Dai Jin-Xing Lu
author_facet	Yuan Wu Chen Liu Wen-Ge Li Jun-Li Xu Wen-Zhu Zhang Yi-Fei Dai Jin-Xing Lu
author_sort	Yuan Wu
title	Independent Microevolution Mediated by Mobile Genetic Elements of Individual <named-content content-type="genus-species">Clostridium difficile</named-content> Isolates from Clade 4 Revealed by Whole-Genome Sequencing
title_short	Independent Microevolution Mediated by Mobile Genetic Elements of Individual <named-content content-type="genus-species">Clostridium difficile</named-content> Isolates from Clade 4 Revealed by Whole-Genome Sequencing
title_full	Independent Microevolution Mediated by Mobile Genetic Elements of Individual <named-content content-type="genus-species">Clostridium difficile</named-content> Isolates from Clade 4 Revealed by Whole-Genome Sequencing
title_fullStr	Independent Microevolution Mediated by Mobile Genetic Elements of Individual <named-content content-type="genus-species">Clostridium difficile</named-content> Isolates from Clade 4 Revealed by Whole-Genome Sequencing
title_full_unstemmed	Independent Microevolution Mediated by Mobile Genetic Elements of Individual <named-content content-type="genus-species">Clostridium difficile</named-content> Isolates from Clade 4 Revealed by Whole-Genome Sequencing
title_sort	independent microevolution mediated by mobile genetic elements of individual <named-content content-type="genus-species">clostridium difficile</named-content> isolates from clade 4 revealed by whole-genome sequencing
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/bfa9327832b84a55a104ed2b974da6e6
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Independent Microevolution Mediated by Mobile Genetic Elements of Individual <named-content content-type="genus-species">Clostridium difficile</named-content> Isolates from Clade 4 Revealed by Whole-Genome Sequencing

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