Matthias Peter Machner, Ph.D.
Section of Microbial Pathogenesis
Host Cell Modulation by the Intracellular Pathogen Legionella pneumophila
Many Gram-negative bacteria use type IV secretion systems (T4SSs) to deliver bacterial effector proteins into host cells, where they modulate signaling events to create an environment supportive of bacterial growth. One of those microbes is Legionella pneumophila, the causative agent of a life-threatening pneumonia called Legionnaires' disease. Upon phagocytosis by alveolar macrophages, L. pneumophila delivers a large number of bacterial proteins, or effectors, into the host-cell cytosol through the Dot/Icm T4SS (Figure 1). Some of those effectors help L. pneumophila redirect proteins and membrane material of the infected cell to its Legionella-containing vacuole (LCV), thereby establishing a protective compartment resembling host-cell endoplasmic reticulum (ER). L. pneumophila mutants with a non-functional T4SS are avirulent, underscoring the importance of the translocated effector proteins for L. pneumophila infection. The main focus of our laboratory is to identify and characterize host-pathogen interactions during L. pneumophila infection and to determine their importance for bacterial virulence.
Dr. Matthias P. Machner graduated from the German college Gymnasium Carolinum of Osnabrueck in 1991. He obtained his Diploma in Biology in 1998 after working with Dr. Hildgund Schrempf at the University of Osnabrueck. Dr. Machner received his Ph.D. degree in Life Sciences (Dr. rer. nat.) from the Carolo Wilhelmina University of Braunschweig, Germany in 2002, graduating with highest distinction (summa cum laude). He then moved to Boston, Massachusetts, where he pursued postdoctoral studies with Dr. Ralph R. Isberg at Tufts University School of Medicine. In 2008, Dr. Machner accepted a tenure-track investigator position in the Cell Biology and Metabolism Program as Head of the Unit on Microbial Pathogenesis. Since then, Dr. Machner’s research has been committed to deciphering the molecular mechanisms underlying Legionnaires’ disease, a severe pneumonia caused by the bacterium Legionella pneumophila. His laboratory recently revealed how L. pneumophila employs post-translational modification in a reversible manner to exploit membrane transport GTPases of infected host cells.
Neunuebel MR, Chen Y, Gaspar AH, Backlund PS Jr, Yergey A, Machner MP. De-AMPylation of the small GTPase Rab1 by the pathogen Legionella pneumophila. Science. 2011;333(6041):453-6.
Gaspar AH, Machner MP. VipD is a Rab5-activated phospholipase A1 that protects Legionella pneumophila from endosomal fusion. Proc Natl Acad Sci U S A. 2014;111(12):4560-5.
Lin YH, Lucas M, Evans TR, Abascal-Palacios G, Doms AG, Beauchene NA, Rojas AL, Hierro A, Machner MP. RavN is a member of a previously unrecognized group of Legionella pneumophila E3 ubiquitin ligases. PLoS Pathog. 2018;14(2):e1006897.
Lucas M, Gaspar AH, Pallara C, Rojas AL, Fernández-Recio J, Machner MP, Hierro A. Structural basis for the recruitment and activation of the Legionella phospholipase VipD by the host GTPase Rab5. Proc Natl Acad Sci U S A. 2014;111(34):E3514-23.
Related Scientific Focus Areas
Microbiology and Infectious Diseases
Molecular Biology and Biochemistry
This page was last updated on August 4th, 2017