Abstract
Yunnan Province, China is thought to be the original source of biovar Orientalis of Yersinia pestis, the causative agent of the third plague pandemic that has spread globally since the end of the 19th century. Although encompassing a large area of natural plague foci, Y. pestis strains have rarely been found in live rodents during surveillance in Yunnan, and most isolates are from rodent corpses and their fleas. In 2017, 10 Y. pestis strains were isolated from seven live rodents and three fleas in Heqing County of Yunnan. These strains were supposed to have low virulence to local rodents Eothenomys miletus and Apodemus chevrieri because the rodents were healthy and no dead animals were found in surrounding areas, as had occurred in previous epizootic disease. We performed microscopic and biochemical examinations of the isolates, and compared their whole-genome sequences and transcriptome with those of 10 high virulence Y. pestis strains that were isolated from nine rodents and one parasitic flea in adjacent city (Lijiang). We analyzed the phenotypic, genomic, and transcriptomic characteristics of live rodent isolates. The isolates formed a previously undefined monophyletic branch of Y. pestis that was named 1.IN5. Six SNPs, two indels, and one copy number variation were detected between live rodent isolates and the high virulence neighbors. No obvious functional consequence of these variations was found according to the known annotation information. Among genes which expression differential in the live rodent isolates compared to their high virulent neighbors, we found five iron transfer related ones that were significant up-regulated (| log2 (FC) | > 1, p.adjust < 0.05), indicating these genes may be related to the low-virulence phenotype. The novel genotype of Y. pestis reported here provides further insights into the evolution and spread of plague as well as clues that may help to decipher the virulence mechanism of this notorious pathogen.
Highlights
Plague is a fatal disease caused by Yersinia pestis, an enterobacteria that has caused three pandemics that have claimed millions of lives (Yang et al, 2011)
354 live rodents were captured and 242 body fleas were collected for Y. pestis detection, and no dead or diseased animals were found around the investigation area
Ten Y. pestis strains were isolated in HQ; six isolates were from Eothenomys miletus (E. miletus), one was from Apodemus chevrieri (A. chevrieri), one was from Ctenophthalmus quadratus, and two were from Neopsylla specialis specialis (N. specialis specialis)
Summary
Plague is a fatal disease caused by Yersinia pestis, an enterobacteria that has caused three pandemics that have claimed millions of lives (Yang et al, 2011). The exception is biovar Microtus, known as 0.PE4 phylogroup (Cui et al, 2013) that is distributed mainly in Inner Mongolia and Qinghai Province, which has low virulence to humans and large mammals but high virulence to the voles Lasiopodomys brandtii and Microtus fuscus (Ji, 1988). As the original source of the third plague pandemic (Morelli et al, 2010), Yunnan Province in China historically has a large area of natural plague foci. In Yunnan, Y. pestis strains have usually been isolated from rodent corpses and their fleas during plague outbreaks, and occasionally from live rodents (Chen, 2019). Rarely have Y. pestis strains been isolated from healthy live rodents, and no dead (rodents that were found dead) or diseased animal was found around the investigation area
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