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Nicholas P. Cianciotto, PhDProfessor
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Legionella pneumophila, ubiquitous in aquatic environments, infects humans following the inhalation of contaminated aerosols released by air-conditioners and other devices. In the respiratory tract, the bacterium invades and grows in macrophages. Intracellular infection and toxin production result in a form of pneumonia known as Legionnaires’ Disease. Interestingly, the ability of L. pneumophila to parasitize macrophages derives from its unique adaptation to growth in aquatic protozoa.
One trait that is required for bacterial pathogenesis is the secretion of proteins that damage tissue, subvert host defenses, and promote nutrient assimilation. We have discovered a secretion system known as type II protein secretion that is critical for Legionella intracellular infection and virulence. Further work has determined that a wide variety of destructive enzymes, including lipases, phospholipases, phosphatases, proteases, and nucleases, are exported via the L. pneumophila type II system. Ongoing efforts are defining the full panel of secretion substrates, their precise role in infection, and the manner in which their expression is regulated.
A second pathogenic characteristic of L. pneumophila is its capacity to scavenge iron. We have isolated many bacterial mutants that are defective for both iron uptake and intracellular infection. Analysis of these strains is uncovering novel effectors of iron acquisition, which include a membrane ferrous iron transporter and an excreted, non-proteinaceous ferric iron chelator, legiobactin.
A third trait that is critical to bacterial survival is the capacity to adhere to surfaces. Work in our laboratory has identified hairlike-projections on L. pneumophila known as type IV pili that promote attachment to macrophages, amoebae, and biofilms. The regulation of pilus expression by temperature and other environmental stimuli is the subject of our additional work.
In sum, our lab uses a multifaceted approach to understand the natural history of Legionnaires’ disease, with the belief that basic insights lead to new methods of disease prevention, diagnosis, and treatment.
Rossier, O., and N. P. Cianciotto. 2005. The Legionella pneumophila tatB Gene Facilitates the Secretion of Phospholipase C, Growth under Iron-Limiting Conditions, and Intracellular Infection. Infect. Immun. 73: 2020-2032.
Cianciotto, N. P., P. Cornelis, and C. Baysse. 2005. Impact of the Bacterial Type I Cytochrome c Maturation System on Different Biological Properties. Mol. Microbiol. 56: 1408-1415.
Cianciotto, N. P. 2005. Type II Secretion: A Protein Secretion System for All Seasons. Trends Microbiol. 13: 581-588.
Allard, K. A., V. K. Viswanathan, and N. P. Cianciotto. 2006. Genes lbtA and lbtB are Required for Production of the Legionella pneumophila Siderophore Legiobactin. J. Bacteriol. 188: 1351-1363.
DebRoy, S., V. Aragon, S. Kurtz, and N. P. Cianciotto. 2006. Legionella pneumophila Mip, a Surface-Exposed Peptidylproline cis-trans Isomerase, Promotes the Presence of Phospholipase C-like Activity in Culture Supernatants. Infect. Immun. 74: 5152-5160.
DebRoy, S., J. Dao, M. Söderberg, O. Rossier, and N. P. Cianciotto. 2006. The Legionella pneumophila Type II Secretome Reveals Unique Exoproteins and a Chitinase that Promotes Bacterial Persistance in the Lungs. Proc. Natl. Acad. Sci. USA. 50: 19146-19151.
Cianciotto, N. P. 2006. Iron Acquisition by Legionella pneumophila. Biometals. Epub ahead of print. DOI 10.1007/s10534-006-9057-4.
Cianciotto, N. P., Y. Abu Kwaik, P. H. Edelstein, B. S. Fields, D. F. Geary, T. G. Harrison, C. A. Joseph, R. M. Ratcliff, Janet E. Stout, and M. S. Swanson. (eds.). 2006. Legionella: State of the Art 30 Years after Its Recognition, ASM Press, Washington, D.C.
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View Publications by Nick Cianciotto listed in the National Library of Medicine (PubMed). |
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