Formation of stress fibres in human endothelial cells infected with Bartonella bacilliformis is associated with altered morphology, impaired migration and defects in cell morphogenesis

Authors

  • Anita Verma,

    1. Department of Medical Biochemistry and Genetics, Texas A and M University System, Health Science Center, College of Medicine, College Station, TX, USA.
    Search for more papers by this author
  • George E. Davis,

    1. Department of Pathology and Laboratory Medicine, Texas A and M University System, Health Science Center, College of Medicine, College Station, TX, USA.
    Search for more papers by this author
  • Garret M. Ihler

    Corresponding author
    1. Department of Medical Biochemistry and Genetics, Texas A and M University System, Health Science Center, College of Medicine, College Station, TX, USA.
    Search for more papers by this author

*For correspondence. E-mail gmihler@tamu.edu; Tel. (+1) 409 845 8686; Fax (+1) 409 847 9481.

Abstract

Bartonella bacilliformis, a Gram-negative, flagellated bacterium, infects human erythrocytes (haematic phase) and endothelial cells (tissue phase), resulting in a biphasic disease. In the tissue phase of disease (verruga peruana), infection leads to infection of endothelial cells and a pronounced proliferation of these cells, resulting in characteristic skin eruptions of papules and nodules. We have studied the properties of endothelial cells infected in vitro. Extensive cytoskeletal remodelling of endothelial cells occurred after infection in vitro with B. bacilliformis. The cells became spindle shaped and contained arrays of actin stress fibres orientated parallel to the long axis of the cell. Cell–cell contacts were disrupted, along with the distribution of the plasma membrane marker protein, PECAM-1, which participates in cell–cell junctions. The prominent stress fibres terminated in an increased number of focal contacts, which were studied using immunofluorescent staining for paxillin, a cytoplasmic protein that localizes in the focal adhesions. These morphological changes are consistent with activation of intracellular Rho by B. bacilliformis. Formation of stress fibres and the increased number of focal adhesions could be prevented by preincubation of the endothelial cells with C3 exoenzyme, which inactivates intracellular Rho by ADP ribosylation. Endothelial cell motility was greatly diminished in infected cells and the cells did not respond effectively to a stimulus that would evoke motility. In addition, infection of endothelial cells interfered with their ability to form networks of capillary tubes when suspended within three-dimensional collagen matrices. If the properties of infected endothelial cells in vivo are similar, the infected cells will probably not participate effectively in angiogenesis.

Ancillary