Matthias Peter Machner, Ph.D.

Senior Investigator

Section of Microbial Pathogenesis

NICHD/DIR

NIHBC 49 - Conte 1A35B
20892-4417

301-435-8417

machnerm@nih.gov

Research Topics

Uncovering Virulence Mechanisms of the Intracellular Pathogen Legionella pneumophila

Infectious diseases have remained a leading cause of death worldwide, especially in young children. Even before the COVID-19 pandemic, respiratory infections were ranked in the top ten causes of death worldwide by the World Health Organization (WHO.gov), particularly in low-income countries. Obtaining a detailed understanding of the underlying virulence mechanisms is of fundamental importance for the development of novel therapeutic approaches to more effectively treat or prevent infectious diseases.

The bacterium Legionella pneumophila is the causative agent of a life-threatening pneumonia called Legionnaires' disease. Upon entering alveolar macrophages, L. pneumophila deliver a large number of bacterial proteins, or effectors, into the host-cell cytosol (Fig. 1). Those effectors help L. pneumophila to manipulate host cell signaling and trafficking processes, thereby establishing a camouflaged compartment, the Legionella-containing vacuole (LCV), that resembles host-cell endoplasmic reticulum (ER). 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.

Biography

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 which has been committed to deciphering the molecular mechanisms underlying Legionnaires’ disease, a severe pneumonia caused by the bacterium Legionella pneumophila. Since approval of his tenure in 2016, Dr. Machner’s has continued his work on L. pneumophila virulence strategies. His laboratory recently made the discovery that the human Hippo pathway, a conserved signaling route best known for its importance in tissue development as well as tumorigenesis, also plays an unexpected role during infection by L. pneumophila.

Selected Publications

  1. Ellis NA, Kim B, Tung J, Machner MP. A multiplex CRISPR interference tool for virulence gene interrogation in Legionella pneumophila. Commun Biol. 2021;4(1):157.

  2. Lee PC, Beyrakhova K, Xu C, Boniecki MT, Lee MH, Onu CJ, Grishin AM, Machner MP, Cygler M. The Legionella kinase LegK7 exploits the Hippo pathway scaffold protein MOB1A for allostery and substrate phosphorylation. Proc Natl Acad Sci U S A. 2020;117(25):14433-14443.

  3. Tascón I, Li X, Lucas M, Nelson D, Vidaurrazaga A, Lin YH, Rojas AL, Hierro A, Machner MP. Structural insight into the membrane targeting domain of the Legionella  deAMPylase SidD. PLoS Pathog. 2020;16(8):e1008734.

  4. Lee PC, Machner MP. The Legionella Effector Kinase LegK7 Hijacks the Host Hippo Pathway to Promote Infection. Cell Host Microbe. 2018;24(3):429-438.e6.

  5. 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.


This page was last updated on November 8th, 2021