Inactivation of sam-methyltransferase is the mechanism of attenuation of a historic louse borne typhus vaccine strain

Yan Liu, Bin Wu, George Weinstock, David Walker, Xue Jie Yu

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Louse borne typhus (also called epidemic typhus) was one of man's major scourges, and epidemics of the disease can be reignited when social, economic, or political systems are disrupted. The fear of a bioterrorist attack using the etiologic agent of typhus, Rickettsia prowazekii, was a reality. An attenuated typhus vaccine, R. prowazekii Madrid E strain, was observed to revert to virulence as demonstrated by isolation of the virulent revertant Evir strain from animals which were inoculated with Madrid E strain. The mechanism of the mutation in R. prowazekii that affects the virulence of the vaccine was not known. We sequenced the genome of the virulent revertant Evir strain and compared its genome sequence with the genome sequences of its parental strain, Madrid E. We found that only a single nucleotide in the entire genome was different between the vaccine strain Madrid E and its virulent revertant strain Evir. The mutation is a single nucleotide insertion in the methyltransferase gene (also known as PR028) in the vaccine strain that inactivated the gene. We also confirmed that the vaccine strain E did not cause fever in guinea pigs and the virulent revertant strain Evir caused fever in guinea pigs. We concluded that a single nucleotide insertion in the methyltransferase gene of R. prowazekii attenuated the R. prowazekii vaccine strain E. This suggested that an irreversible insertion or deletion mutation in the methyl transferase gene of R. prowazekii is required for Madrid E to be considered a safe vaccine.

Original languageEnglish (US)
Article numbere113285
JournalPLoS One
Volume9
Issue number11
DOIs
StatePublished - Nov 20 2014

Fingerprint

Rickettsia prowazekii
typhus
Phthiraptera
lice
methyltransferases
Methyltransferases
inactivation
Genes
vaccines
Epidemic Louse-Borne Typhus
Vaccines
Genome
Nucleotides
Virulence
Guinea Pigs
Fever
genome
Political Systems
nucleotides
INDEL Mutation

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Inactivation of sam-methyltransferase is the mechanism of attenuation of a historic louse borne typhus vaccine strain. / Liu, Yan; Wu, Bin; Weinstock, George; Walker, David; Yu, Xue Jie.

In: PLoS One, Vol. 9, No. 11, e113285, 20.11.2014.

Research output: Contribution to journalArticle

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