Evolutionary and genomic insights into the long-term colonization of Shigella flexneri in animals

ABSTRACT

The enteroinvasive bacterium Shigella flexneri is known as a highly host-adapted human pathogen. There had been no known other reservoirs reported until recently. Here 34 isolates obtained from animals (yaks, dairy cows and beef cattle) from 2016 to 2017 and 268 human S. flexneri isolates from China were sequenced to determine the relationships between animal and human isolates and infer the evolutionary history of animal-associated S. flexneri. The 18 animal isolates (15 yak and 3 beef cattle isolates) in PG1 were separated into 4 lineages, and the 16 animal isolates (1 yak, 5 beef cattle and 10 dairy cow isolates) in PG3 were clustered in 8 lineages. The most recent human isolates from China belonged to PG3 whereas Chinese isolates from the 1950s–1960s belonged to PG1. PG1 S. flexneri may has been transmitted to the yaks during PG1 circulation in the human population in China and has remained in the yak population since, while PG3 S. flexneri in animals were likely recent transmissions from the human population. Increased stability of the large virulence plasmid and acquisition of abundant antimicrobial resistance determinants may have enabled PG3 to expand globally and replaced PG1 in China. Our study confirms that animals may act as a reservoir for S. flexneri. Genomic analysis revealed the evolutionary history of multiple S. flexneri lineages in animals and humans in China. However, further studies are required to determine the public health threat of S. flexneri from animals.

KEYWORDS:

• Shigella flexneri
• phylogenetic analysis
• SNP typing
• animal reservoir
• evolution

Disclosure statement

No potential conflict of interest was reported by the author(s).

Author contributions

Jianguo Xu and Ruiting Lan conceived the study. Zhen Zhu, Shan Lu, Dong Jin, Jing Yang, Jianping Wang, Kui Dong, Mingchao Xu and Junrong Liang collected the samples and isolated the strains. Bram Vrancken and Huaiyu Tian performed the temporal analysis. Junrong Liang, Jing Meng, Li Zhang, TaiJiao Jiang and Ji Pu performed the other bioinformatic analysis. Junrong Liang, Jianguo Xu, Ruiting Lan, Bram Vrancken and Li Zhang wrote the manuscript. Ruiting Lan, TaiJiao Jiang and Tian Qin provided critical analysis and discussions.

Data availability

Sequencing data were submitted to the Sequence Read Archive (SRA) with the project number PRJNA820478 (The strains used are listed in Supplementary file 1).

Additional information

Funding

This work was supported by the National Key Research and Development Program of China (2019YFC1200505 and 2021YFC2302000); Research Units of Discovery of Unknown Bacteria and Function (2018RU010); the National Natural Science Foundation of China (32070678); the Emergency Key Program of Guangzhou Laboratory (EKPG21-12); and CAMS Innovation Fund for Medical Sciences (CIFMS) (2021-I2M-1-061).