Bacterial pathogenesis

Prophages of Staphylococcus aureus Newman and their contribution to virulence Bae, T., Baba, T., Hiramatsu, K. & Schneewind, O. Mol. Microbiol. 67, 1035–1047 (2006)

Hospital-acquired infections of surgical wounds and those associated with indwelling medical devices are potentially life-threatening. The main cause of these infections is Staphylococcus aureus, which also causes numerous other pus-forming infections and toxinoses. Although most S. aureus virulence factors are chromosomally-encoded, recent studies have linked prophage functions to pathogenesis. Now the latest study from the Schneewind laboratory proves that S. aureus strain Newman (a human clinical isolate) prophages are essential for virulence in nematodes and rodents. There are four prophages that encode innate immune modulatory genes and toxins present in the genome of this strain. Intriguingly, the excision and loss of individual prophages altered virulence in an organ-specific manner, and loss of all four prophages rendered the strain avirulent.

Toxins

Pseudomonas aeruginosa type III-secreted toxin ExoT inhibits host-cell division by targeting cytokinesis at multiple steps Shafikhani, S. H. & Engel, J. Proc. Natl Acad. Sci USA 09 October 2006 (doi: 10.1073/pnas.0605949103)

Acute infections caused by Pseudomonas aeruginosa commonly occur in immunocompromised individuals or those who have wounds. This important opportunistic pathogen also colonizes the lungs of cystic fibrosis patients. Damage to the host is dependent on the functions of effector proteins that are translocated into eukaryotic cells by the bacterial type III secretion system apparatus. Although the complement of effectors produced differs among clinical strains of P. aeruginosa most strains produce the toxin ExoT. This paper shows that both domains of the bifunctional ExoT protein are required to inhibit cytokinesis in host epithelia, which directly inhibits wound-healing in the host. This new virulence tactic serves to maintain the damaged host environment and facilitate bacterial proliferation.

Viral pathogenesis

Insulin-degrading enzyme is a cellular receptor mediating varicella-zoster virus infection and cell-to-cell spread Li, Q., Ali, M. A. & Cohen, J. I. Cell 127, 305–316 (2006)

Varicella-zoster virus (VZV), a member of the α-herpesvirus family, causes chickenpox (varicella), which has a characteristic rash, then establishes a latent infection in the nervous system. Reactivation of VZV infection can subsequently cause shingles (zoster). Inside the body, virus transmission is by cell-to-cell spread. The glycoprotein E gene of VZV, which is essential for virus infection, and the herpes simplex virus-1 glycoprotein D gene, which codes for the protein that binds to host receptor proteins in this related virus, are found in the same region of the viral genomes. Here, the authors showed that VZV glycoprotein E binds to host-cell insulin-degrading enzyme (IDE). Downregulation of IDE affected transmission of cell-free and cell-associated VZV but did not block transmission completely, so the authors are still looking for additional host-cell receptors for this virus.