EDITORIAL
Plague, a zoonotic disease transmitted from rodents via fleabites, caused three large pandemics, each decimating human populations with profound effects on civilization. What is the basis for the deadly consequences of plague infection? To address this question, Lee Kupferberg and Kiyoshi Higuchi studied the nutritional requirements of Yersinia pestis (then called Pasteurella pestis), the causative agent of plague. In a classic Journal of Bacteriology paper, the authors observed that Y. pestis requires calcium ions for growth at 37°C, the ambient temperature of vertebrate hosts, but not at lower temperatures (27°C) typical of flea colonization (1). Growth restriction of Y. pestis in media lacking calcium ions was found to be associated with virulence in a mouse model of plague disease (1). Y. pestis variants that do not display the low-calcium response phenotype (LCR−) are avirulent and were readily isolated when virulent plague strains were propagated at 37°C without calcium (2).
Following the discovery that Y. pestis calcium dependence and virulence are dependent on a 70-kb plasmid (pCD1) (3, 4), transposon mutagenesis was used to identify the genetic determinants of the LCR (5). This approach yielded also mutants with a new phenotype, designated calcium blind, as such variants cease growth at 37°C irrespective of the presence or absence of calcium ions (6). Two other classic Journal of Bacteriology papers revealed that plasmid-carried genes promote the secretion of Yersinia outer proteins (Yops) by a pathway now designated type III secretion. Thomas Michiels and Guy Cornelis first demonstrated that Yop proteins accumulate in large abundance in media of Yersinia cultures propagated without calcium and that secretion occurs by a signal peptide-independent mechanism (7, 8). The team also revealed the predicted amino acid sequences of virulence plasmid-encoded secretion proteins, laying foundations for the study of type III secretion in other bacteria (9).
pCD1-encoded type III secretion is essential for the pathogenesis of plague infections (10). Penetration of Y. pestis type III secretion needles into the plasma membrane of immune cells presumably enables bacteria to perceive the low-calcium environment of the host cell cytoplasm, triggering the low-calcium response with large-scale synthesis and secretion of Yops (11, 12). The type III secretion pathway is not unique to Y. pestis and has been characterized in other bacteria carrying virulence plasmids or chromosomal pathogenicity islands.
The views expressed in this Editorial do not necessarily reflect the views of the journal or of ASM.
REFERENCES
- 1.Kupferberg LL, Higuchi K. 1958. Role of calcium ions in the stimulation of growth of virulent strains of Pasteurella pestis. J Bacteriol 76:120–121. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Higuchi K, Kupferberg LL, Smith JL. 1959. Studies on the nutrition and physiology of Pasteurella pestis. III. Effects of calcium ions on the growth of virulent and avirulent strains of Pasteurella pestis. J Bacteriol 77:317–321. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Ben-Gurion R, Shafferman A. 1981. Essential virulence determinants of different Yersinia species are carried on a common plasmid. Plasmid 5:183–187. [DOI] [PubMed] [Google Scholar]
- 4.Ferber DM, Brubaker RR. 1981. Plasmids in Yersinia pestis. Infect Immun 31:839–841. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Goguen JD, Yother J, Straley SC. 1984. Genetic analysis of the low calcium response in Yersinia pestis Mu d1(Ap lac) insertion mutants. J Bacteriol 160:842–848. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Yother J, Goguen JD. 1985. Isolation and characterization of Ca2+-blind mutants of Yersinia pestis. J Bacteriol 164:704–711. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Michiels T, Cornelis GR. 1991. Secretion of hybrid proteins by the Yersinia Yop export system. J Bacteriol 173:1677–1685. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Michiels T, Wattiau P, Brasseur R, Ruysschaert J-M, Cornelis G. 1990. Secretion of Yop proteins by yersiniae. Infect Immun 58:2840–2849. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Michiels T, Vanooteghem J-C, Lambert de Rouvroit C, China B, Gustin A, Boudry P, Cornelis GR. 1991. Analysis of virC, an operon involved in the secretion of Yop proteins by Yersinia enterocolitica. J Bacteriol 173:4994–5009. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Perry RD, Harmon PA, Bowmer WS, Straley SC. 1986. A low-Ca2+ response operon encodes the V antigen of Yersinia pestis. Infect Immun 54:428–434. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Torruellas J, Jackson MW, Pennock JW, Plano GV. 2005. The Yersinia pestis type III secretion needle plays a role in the regulation of Yop secretion. Mol Microbiol 57:1719–1733. doi: 10.1111/j.1365-2958.2005.04790.x. [DOI] [PubMed] [Google Scholar]
- 12.Marketon MM, DePaolo RW, DeBord KL, Jabri B, Schneewind O. 2005. Plague bacteria target immune cells during infection. Science 309:1739–1741. doi: 10.1126/science.1114580. [DOI] [PMC free article] [PubMed] [Google Scholar]