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Structure, dynamics and cellular insight into novel substrates of the Legionella pneumophila type II secretion system

DOI: 10.3389/fmolb.2020.00112 DOI Help

Authors: Theo J. Portlock (King’s College London; Queen Mary University of London) , Jessica Y. Tyson (Northwestern University Feinberg School of Medicine) , Sarath C. Dantu (Brunel University London) , Saima Rehman (King’s College London) , Richard C. White (Northwestern University Feinberg School of Medicine) , Ian E. Mcintire (Northwestern University Feinberg School of Medicine) , Lee Sewell (King’s College London) , Katherine Richardson (Queen Mary University of London) , Rosie Shaw (Queen Mary University of London) , Alessandro Pandini (Brunel University London) , Nicholas P. Cianciotto (Northwestern University Feinberg School of Medicine) , James Garnett (King’s College London; Queen Mary University of London)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Frontiers In Molecular Biosciences , VOL 7

State: Published (Approved)
Published: June 2020
Diamond Proposal Number(s): 7299 , 21035

Open Access Open Access

Abstract: Legionella pneumophila is a Gram-negative bacterium that is able to replicate within a broad range of aquatic protozoan hosts. L. pneumophila is also an opportunistic human pathogen that can infect macrophages and epithelia in the lung and lead to Legionnaires’ disease. The type II secretion system is a key virulence factor of L. pneumophila and is used to promote bacterial growth at low temperatures, regulate biofilm formation, modulate host responses to infection, facilitate bacterial penetration of mucin gels and is necessary for intracellular growth during the initial stages of infection. The L. pneumophila type II secretion system exports at least 25 substrates out of the bacterium and several of these, including NttA to NttG, contain unique amino acid sequences that are generally not observed outside of the Legionella genus. NttA, NttC, and NttD are required for infection of several amoebal species but it is unclear what influence other novel substrates have within their host. In this study, we show that NttE is required for optimal infection of Acanthamoeba castellanii and Vermamoeba vermiformis amoeba and is essential for the typical colony morphology of L. pneumophila. In addition, we report the atomic structures of NttA, NttC, and NttE and through a combined biophysical and biochemical hypothesis driven approach we propose novel functions for these substrates during infection. This work lays the foundation for future studies into the mechanistic understanding of novel type II substrate functions and how these relate to L. pneumophila ecology and disease.

Journal Keywords: Legionella pneumophila; effector; type II secretion system; structure; dynamics; NttA; NttC; NttE

Diamond Keywords: Legionnaires' Disease; Bacteria

Subject Areas: Biology and Bio-materials, Chemistry

Instruments: B21-High Throughput SAXS , I04-Macromolecular Crystallography

Added On: 11/06/2020 13:27

Discipline Tags:

Pathogens Infectious Diseases Health & Wellbeing Biochemistry Chemistry Structural biology Biophysics Life Sciences & Biotech

Technical Tags:

Diffraction Scattering Macromolecular Crystallography (MX) Small Angle X-ray Scattering (SAXS)