Pathogenic Mechanisms of the Legionnaires’ Disease Bacterium Howard Steinman, PhD Professor howard.steinman@einsteinmed.org 718.430.3010 Belfer 211 E The fresh water bacterium, Legionella pneumophila, is the causative agent of Legionnaires’ disease, a potentially fatal pneumonia spread by aerosolization of the bacterium from air conditioning systems, shower heads and humidifying devices. This highly-publicized outbreak in Manhattan emphasized the importance of Legionella in community public health education. New York Times JUNE 16, 2017Legionnaires’ Outbreak on Upper East Side Kills One and Sickens Six By SARAH MASLIN NIR One person is dead and six other people have been sickened in an outbreak of Legionnaires’ disease on the Upper East Side of Manhattan, the city health department announced on Friday. …“We know that this is an organism that exists in our environment, and we don’t expect to be able to eradicate it,” said Dr. Mary T. Bassett, the health commissioner. “From a public health point of view, we want to be able to get a handle on clusters that may have a common source, but we hardly ever are able to identify them.” The ability of L. pneumophila to replicate within and evade killing by pulmonary macrophages requires a Type Four Secretion System (TFSS) which secretes Legionella proteins into host cells. These bacterial proteins then influence the fate of internalized Legionella. Research in my laboratory demonstrated that following exposure to conditions that mimic the fresh water environment Legionella, the Dot/Icm T4SS—previously associated with all virulence phenotypes—is no longer required. We implicated the Lvh T4SS as a functional alternative to the Dot/Icm T4SS. The Lvh T4SS is of particular interest because its locus is on a mobile genetic element, pLP45, that can exist either integrated in the bacterial chromosome or excised as an episomal element. Excision of pLP45 interrupts a non coding RNA, lpr0035, that is essential for efficient replication of L. pneumophila in macrophage and amoebae hosts. Selected References Jayakumar, D., Early, J.V. and Steinman, H.M. (2012) Virulence phenotypes of Legionella pneumophila associated with noncoding RNA lpr0035. Infection and Immunity 80, 4143-4153. Bandyopadhyay, P., Lang, E.A, Rasaputra, K.S. and Steinman, H.M. (2013) Implication of the VirD4 Coupling Protein of the Lvh Type 4 Secretion System in Virulence Phenotypes of Legionella pneumophila. J Bacteriol. 195, 3468-75. Although my laboratory is now closed, I continue to advise Biochemistry students on Journal Club and WIP presentations. I also teach in the Graduate School Human Metabolism and Disease course. As Einstein's Assistant Dean for Biomedical Science Education, I teach MD students and play an active role in the Office of Medical Education in curricular change, educational administration and integration of foundation science with clinical curriculum.