J Korean Soc Microbiol.  1998 Apr;33(2):163-174.

Study on the Antigen Composition and Intracellular Viability in Macrophage of aroA Mutants Generated from the Korean Isolates, Shigella sonnei KNIH 104S

• Ju YR
• Kim YC
• Lim YJ
• Song TH
• Lee KJ
• Bae YS

Abstract

Shigella is a major causative agent for bacillary dysentery among the children in developing countries. In order to develop live vaccines against enteric pathogens, we have selected slightly attenuated Shigella sonnei KNIH104S from the Korean patients. The clone was further attenuated by aroA mutation through a genetic recombination experiment. Three aroA deletion mutants were newly selected as vaccine candidates based on their LDSO values in mice, and then named 104-7A, 104-7B and 104-7C. These attenuated strains were tested for their antigen composition and resistancy to macrophage. We found that 7A and 7B are similar in antigen composition and immunogenicity, but are different from 7C in some aspects. Interestingly, all of the three have couple of distinguished antigen components which are not immunogenic in wild type 104S, but are strongly immunogenic in aroA mutants. These three strains, even though highly attenuated, are much more potent in the immunogenicity than 104S. Unexpectedly, 104S was rarely detected in mouse macrophage when exposed to the macrophages, but grew well in eukaryotic media without supplimentation of para-hydroxybenzoic acid (PHBA), indicating that 104S is evasive to the phagocytosis of mouse macrophage, resulting in toxic to the host. Whereas, three attenuated strains are easily phagocytosed but resistant, to some extent, to mouse macrophages. Nevertheless, they are likely to be developed as vaccine candidates because their viability are strongly inhibited in the absense of PHBA in eukaryotic media. These data achieved from the viability test in mouse macrophage remain to be analyzed further in association with the biological function of large virulent plasmid in Shigella.

MeSH Terms

Animals
Child
Clone Cells
Developing Countries
Dysentery, Bacillary
Humans
Macrophages*
Mice
Phagocytosis
Plasmids
Recombination, Genetic
Shigella sonnei*
Shigella*
Vaccines
Vaccines