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Yersinia pestis pH 6 antigen forms fimbriae and is induced by intracellular association with macrophages
1Department of Immunology, Walter Reed Army Institute of Research, Washington, D.C. 20307-5100.
Abstract:
Ability to express pH 6 antigen (Ag) is necessary for full virulence of Yersinia pestis; however, the function of the Ag in pathogenesis remains unclear. We determined the nucleotide sequence of a 4232 bp region of Y. pestis DNA which encoded the pH 6 Ag structural gene (psaA) and accessory loci necessary for Ag synthesis. Protein sequences encoded by the Y. pestis DNA were similar to accessory proteins which function in the biosynthesis of Escherichia coli fimbriae Pap, K88, K99 and CS3 as well as the molecular chaperone for the Y. pestis capsule protein. Electron microscopy and immunogold labelling studies revealed that pH 6 Ag expressing E. coli or Yersinia produced flexible 'fibrillar' organelles composed of individual linear strands, multiple strand bundles or wiry aggregates of PsaA. Y. pestis associated with the murine macrophage-like cell line, RAW264.7, expressed pH 6 Ag in an intracellular acidification-dependent manner. Together with an earlier study showing that a Y. pestis psaA mutant was reduced in virulence, these results demonstrate that the expression of fimbriae which are induced in host macrophages is involved in plague pathogenesis.
Insights
The pH 6 antigen (Ag) in Yersinia pestis, crucial for virulence, forms fibrillar structures. Its expression in macrophages is vital for plague pathogenesis, highlighting its role in infection.
Area of Science:
- Microbiology
- Pathogenesis
- Molecular Biology
Background:
- The pH 6 antigen (Ag) of Yersinia pestis is essential for full virulence, but its precise role in pathogenesis is not fully understood.
- Understanding the molecular mechanisms behind Y. pestis virulence factors is critical for developing effective countermeasures against plague.
Purpose of the Study:
- To elucidate the function of the pH 6 antigen (Ag) in Yersinia pestis pathogenesis.
- To characterize the genetic loci and structural components involved in pH 6 Ag expression and its role in bacterial-host interactions.
Main Methods:
- Nucleotide sequencing of the Y. pestis DNA region encoding the pH 6 Ag structural gene (psaA) and accessory loci.
- Comparative analysis of protein sequences with known fimbrial accessory proteins and molecular chaperones.
- Electron microscopy and immunogold labeling to visualize pH 6 Ag structures on bacterial surfaces.
- In vitro studies using the RAW264.7 macrophage cell line to assess pH 6 Ag expression under different conditions.
Main Results:
- The 4232 bp DNA region contained the psaA gene and accessory loci necessary for pH 6 Ag synthesis.
- Encoded proteins showed similarity to accessory proteins involved in Escherichia coli fimbriae biosynthesis and Y. pestis capsule protein chaperones.
- pH 6 Ag expressing bacteria formed flexible, fibrillar organelles composed of PsaA.
- Y. pestis expressed pH 6 Ag in a manner dependent on intracellular acidification within macrophages.
Conclusions:
- The pH 6 Ag of Y. pestis forms fibrillar structures, likely fimbriae, involved in pathogenesis.
- Expression of these fimbriae is induced within host macrophages and is dependent on intracellular acidification.
- The findings demonstrate that pH 6 Ag-expressing fimbriae play a significant role in plague pathogenesis, linking bacterial surface structures to virulence.