Plague genome suggests organism evolved from gut to blood pathogen

Oct 10, 2001 (CIDRAP News) – Genetic mapping of Yersinia pestis, the agent that causes plague, indicates that the organism used numerous genes collected from other bacteria and viruses to change from a relatively innocuous enteric pathogen into a lethal bloodborne pathogen, according to a report in the Oct 4 issue of Nature.

"Y. pestis seems to have rapidly adapted from being a mammalian enteropathogen widely found in the environment, to a blood-borne pathogen of mammals that is also able to parasitize insects and has limited capability for survival outside these hosts," says the article by J. Parkhill of the Sanger Center in Cambridge, United Kingdom, and colleagues from there and several other British centers. The article reports on the complete gene sequencing of the organism.

Y pestis caused pandemics of plague in the sixth to eighth centuries and in the 14th century and still causes some cases of pneumonic and bubonic plague each year, the report notes. The organism is usually transmitted from rodents to humans via flea bites, but airborne transmission can also occur. It is considered a potential biological weapon. Y pestis is very closely related to the gastrointestinal pathogen Yersinia pseudotuberculosis, and other authors have proposed that it evolved from the latter species sometime between 1,500 and 20,000 years ago, the article notes.

The authors sequenced the genome of Y pestis CO92 (biovar Orientalis), a strain that was isolated from a person who died of pneumonic plague contracted from an infected cat. They report that the genome consists of a 4.65-megabase (Mb) chromosome and three plasmids composed of 96.2 kilobases (kb), 70.3 kb, and 9.6 kb. "Many genes seem to have been acquired from other bacteria and viruses (including adhesins, secretion systems and insecticidal toxins)," the report states. Two of the plasmids encode a variety of virulence determinants acquired from other organisms, and the chromosome includes several genes that seem to have come from other insect pathogens.

"Horizontal gene acquisition in Y. pestis has been balanced by gene loss," the article states. The genome includes 149 pseudogenesgenes that were rendered inactive by various mechanisms as the organism evolved from an enteric pathogen to a bloodborne pathogen. Y pestis lost "genes that were either not required in its new niche, or [that] may have decreased fitness for a new lifestyle as a systemic pathogen of mammals and an insect pathogen." Examples include genes that encode for proteins that enteric pathogens use to stick to and invade cells lining the gut. Comparison of the Y pestis pseudogenes with the corresponding genes in Y pseudotuberculosis indicates that most of the Y pestis mutations are recent, the authors add.

"The genome sequence of Y pestis reveals a pathogen that has undergone considerable genetic flux, with evidence of selective genome expansion by lateral gene transfer of plasmid and chromosomal genes, and subsequent initial stages of genome size reduction," the authors conclude. "We believe that these features correlate with a change in pathogenic niche, and therefore this genome sequence provides a unique insight into the genetic events that are associated with the emergence of a new pathogenic species."

Parkhill J, Wren BW, Thomson NR, et al. Genome sequence of Yersinia pestis, the causative agent of plague. Nature 2001 Oct 4;413(6855):523-7 [Abstract]

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