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Pathoadaptation of the Intracellular Bacteria Shigella and Chlamydia: Virulence, Antivirulence, and Tissue Tropism

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Technical Report

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Uniformed Services University Of The Health Sciences Bethesda United States

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Horizontal transfer of pathogenicity islands or plasmids can enable bacterial adaptation to novel pathogenic niches. Success in the new niche is dependent on conservation of advantageous genes and concomitant inactivation or loss of deleterious or unnecessary alleles. For example, the acquisition of type three secretion systems T3SSs by Shigella and Chlamydia species facilitated entry into and exploitation of eukaryotic host cells. Conversely, both microbes experienced significant pseudogenization and genome reduction as a result of adaptation to the intracellular lifestyle. The pathogenic Shigella evolved from commensal Escherichia coli ancestors following acquisition of a large virulence plasmid carrying the T3SS. Antivirulence genes AVGs inhibitory to the new intracellular niche have been inactivated or lost from all strains. To identify novel Shigella AVGs, a contracted version of the large virulence plasmid was created using the minimal genes required for T3SS expression and assembly. Termed the Shigella minimally invasive plasmid Smip, this construct was transformed into a S. flexneri strain cured of the large virulence plasmid BS103, and the virulence phenotypes of the resulting strain characterized. BS103Smip was capable of host cell entry, demonstrating the presence of a functional T3SS. However, although expression of the Smip in commensal E. coli isolates permitted host cell entry, invasion was severely attenuated compared to wild type Shigella. In two E. coliSmip isolates, T3SS expression was severely inhibited at the level of the T3SS transcriptional regulators, virF and virB, indicating that that multiple virulence inhibitors potential AVGs are likely present in these strains. As part of a second project exploring pathogen evolution, the activity and expression of the arginine decarboxylase enzyme AaxB in Chlamydia was examined. Chlamydia species infect a wide variety of different hosts and tissues.


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