Comparative genome analysis of 15 clinical <em>Shigella flexneri</em> strains regarding virulence and antibiotic resistance

Liang Wang; Zuobin Zhu; Huimin Qian; Ying Li; Ying Chen; Ping Ma; Bing Gu; Liang Wang; Zuobin Zhu; Huimin Qian; Ying Li; Ying Chen; Ping Ma; Bing Gu

doi:10.3934/microbiol.2019.3.205

AIMS Microbiology

2019, Volume 5, Issue 3: 205-222. doi: 10.3934/microbiol.2019.3.205

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Research article

Comparative genome analysis of 15 clinical Shigella flexneri strains regarding virulence and antibiotic resistance

1.
Department of Bioinformatics, School of Medical Informatics and Engineering, Xuzhou Medical University, Xuzhou 221000, Jiangsu China
2.
Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou 221000, Jiangsu China
3.
Department of Genetics, School of Life Sciences, Xuzhou Medical University, Xuzhou, Jiangsu, China
4.
Jiangsu Provincial Center for Disease Control and Prevention, Nanjing 210009, China
5.
Medical Technology School of Xuzhou Medical University, Xuzhou 221004, China
6.
Department of Laboratory Medicine, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221006, China

Received: 20 June 2019 Accepted: 07 August 2019 Published: 13 August 2019

Shigellosis is the major cause of dysentery globally. It is mainly attributed to two Shigella species, Shigella sonnei and Shigella flexneri, which leads to approximately 165 million infections and 1.1 million deaths each year. Rapid increase and widening of spectrum in antibiotics resistance make Shigella hard to be adequately controlled through existing prevention and treatment measures. It has also been observed that enhanced virulence and advent of antibiotic resistance (AR) could arise almost simultaneously. However, genetic linkages between the two factors are missing or largely ignored, which hinders experimental verification of the relationship. In this study, we sequenced 15 clinically isolated S. flexneri strains. Genome assembly, annotation and comparison were performed through routine pipelines. Differential resistant profiles of all 15 S. flexneri strains to nine antibiotics were experimentally verified. Virulence factors (VFs) belonging to 4 categories and 31 functional groups from the Virulence Factor Database (VFDB) were used to screen all Shigella translated CDSs. Distribution patterns of virulence factors were analysed by correlating with the profiles of bacterial antibiotics resistance. In addition, multi-resistant S. flexneri strains were compared with antibiotic-sensitive strains by focusing on the abundance or scarcity of specific groups of VFs. By doing these, a clear view of the relationships between virulence factors and antibiotics resistance in Shigella could be achieved, which not only provides a set of genetic evidence to support the interactions between VFs and AR but could also be used as a guidance for further verification of the relationships through manipulating specific groups of virulence factors.
- Shigella,
- virulence factor,
- comparative genomics,
- antibiotics resistance,
- HMMER,
- Prokka
Citation: Liang Wang, Zuobin Zhu, Huimin Qian, Ying Li, Ying Chen, Ping Ma, Bing Gu. Comparative genome analysis of 15 clinical Shigella flexneri strains regarding virulence and antibiotic resistance[J]. AIMS Microbiology, 2019, 5(3): 205-222. doi: 10.3934/microbiol.2019.3.205

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Abstract

Shigellosis is the major cause of dysentery globally. It is mainly attributed to two Shigella species, Shigella sonnei and Shigella flexneri, which leads to approximately 165 million infections and 1.1 million deaths each year. Rapid increase and widening of spectrum in antibiotics resistance make Shigella hard to be adequately controlled through existing prevention and treatment measures. It has also been observed that enhanced virulence and advent of antibiotic resistance (AR) could arise almost simultaneously. However, genetic linkages between the two factors are missing or largely ignored, which hinders experimental verification of the relationship. In this study, we sequenced 15 clinically isolated S. flexneri strains. Genome assembly, annotation and comparison were performed through routine pipelines. Differential resistant profiles of all 15 S. flexneri strains to nine antibiotics were experimentally verified. Virulence factors (VFs) belonging to 4 categories and 31 functional groups from the Virulence Factor Database (VFDB) were used to screen all Shigella translated CDSs. Distribution patterns of virulence factors were analysed by correlating with the profiles of bacterial antibiotics resistance. In addition, multi-resistant S. flexneri strains were compared with antibiotic-sensitive strains by focusing on the abundance or scarcity of specific groups of VFs. By doing these, a clear view of the relationships between virulence factors and antibiotics resistance in Shigella could be achieved, which not only provides a set of genetic evidence to support the interactions between VFs and AR but could also be used as a guidance for further verification of the relationships through manipulating specific groups of virulence factors.

Acknowledgments

This work was supported by the National Natural Science Foundation of China (81871734, 81471994), Jiangsu Provincial Natural Science Foundation (BK20151154, BK20180997), Jiangsu Provincial Medical Talent (ZDRCA2016053), Six Talent Peaks Project of Jiangsu Province (WSN-135), Advanced Health Talent of Six-one Project of Jiangsu Province (LGY2016042), and Jiangsu Provincial Commission of Health and Family Planning Research Project (H201631), Startup Foundation for Excellent Researchers at Xuzhou Medical University (No. D2016007), The Natural Science Foundation of the Jiangsu Higher Education Institutions of China (No. 17KJB360014, No. 16KJB180028), and Innovative and Entrepreneurial Talent Scheme of Jiangsu Province (2017). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.

Author contribution

BG, LW, and ZZ proposed the core ideas of the study and designed the experiment. HQ, YL, and YC did all the experiments for bacterial sequencing. BG, LW, ZZ, and PM performed all the data analysis. All authors contribute to the writing of the manuscript.

Conflict of interest

The authors declare that they have no conflict of interest.

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