Do you think that infectious diseases are spread from a sick person to someone who is not infected? While many infectious diseases are, Legionnaires’ disease, a potentially fatal pneumonia, is not. Legionella pneumophila, the causative organism, attains an infectious inoculum by replicating in fresh water amoebae, then spreads to humans by aerosolization from air conditioning systems, shower heads and humidifying devices. The ability of L. pneumophila to enter, evade phagosome acidification and replicate in eukaryotic cells is dependent on a type four secretion system (T4SS) that transfers Legionella proteins into hosts. These bacterial proteins then influence the fate of internalized Legionella.

Research in our laboratory demonstrated that following exposure to conditions that mimic the fresh water environment of Legionella, the Dot/Icm T4SS, previously associated with all virulence phenotypes, is no longer required. The focus of our research is the Lvh T4SS, which we implicated as a functional alternative to the Dot/Icm T4SS. The locus encoding the Lvh T4SS is on a mobile genetic element that can integrate in the bacterial chromosome or excise as an episomal element.

Our experimental approaches include: in vitro studies of pathogenic phenotypes in macrophages and amoeba, yeast two hybrid identification of interacting proteins, immunological analysis of protein localization within the bacterial cell and, in collaboration with Shawn Skerrett at the University of Washington, animal model studies in mice.

The questions we are asking are

• Can protein components of the Lvh T4SS functionally substitute for components of the Dot/Icm T4SS?
• Are particular T4SS substrates preferentially transported by the Lvh T4SS or the Dot/Icm T4SS?
• Are these two T4SSs localized at different regions of the Legionella bacterial cell?
• Are virulence phenotypes of Legionella influenced by the mobility of the Lvh T4SS?
• What is the role of tetratricopeptide repeat-containing proteins, generally associated with protein-protein interactions, in pathogenic mechanisms of Legionella?

Bandyopadhyay, P. and Steinman, H.M. (2000) J. Bacteriol. 182, 6679-6686. Catalase-Peroxidases of Legionella pneumophila: Cloning of the katA Gene and Studies of KatA Function.

http://jb.asm.org/content/182/23/6679.full.pdf+html

Bandyopadhyay, P., Byrne, B., Chan, Y., Swanson, M., and Steinman, H.M. (2003)  Infect. Immun. 71, 4526-4535.
The Legionella pneumophila catalase-peroxidases are required for proper trafficking and growth in primary macrophages

http://iai.asm.org/content/71/8/4526.full.pdf+html

Bandyopadhyay, P., Xiao, H., Coleman, H.A. Price-Whelan, A., and Steinman, H.M. (2004) Infect. Immun. 72, 4541-51.
Icm/Dot-independent entry of Legionella pneumophila into amoeba and macrophage hosts

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC470674/pdf/0547-04.pdf

Bandyopadhyay, P., Liu, S., Gabbai, C.B., Venitelli, Z., and Steinman, H.M. (2007) Infect. Immun. 75, 723-35.
Environmental mimics and the Lvh type IVA secretion system contribute to virulence-related phenotypes of Legionella pneumophila

http://iai.asm.org/content/75/2/723.full.pdf+html

Bandyopadhyay, P., Sumer, E.U., Jayakumar, D., Liu, S., Xiao, H., and Steinman, H.M. (2012) J. Bacteriol. 194, 3579-88. Implication of proteins containing tetratricopeptie repeats in conditional virulence phenoptyes virulence of Legionella pneumophila

http://jb.asm.org/content/194/14/3579.full.pdf+html

Jayakumar, D., Early, J.V. and Steinman, H.M. (2012) Infection and Immunity 80, 4143-4153. Virulence phenotypes of Legionella pneumophila associated with non-coding RNA lpr0035

http://iai.asm.org/content/80/12/4143.full.pdf+html

Bandyopadhyay, P., Lang, E.A., Rasaputra, K.S., and Steinman, H.M. (2013) J. Bacteriol. 195, 3468-3475. Implication of the VirD4 coupling proteinn of the Lvh type 4 secretion system in virulence phenotypes of Legionella pneumophila

http://jb.asm.org/content/195/15/3468.full.pdf+html