Andreas Diepold, PhD

Bacterial Secretion Systems

Curriculum Vitae

Andreas Diepold (born 1980)
Diploma (Biochemistry), Universität Tübingen, Germany, 1999-2005
University of North Carolina, Greenville, NC, USA, 2002-2003
Research assistant, Novartis Institute for Biomedical Research, Basel, Switzerland, 2005-2006
PhD (Biochemistry and Microbiology), Biozentrum, University of Basel, Switzerland, 2006-2010
Hiroshima Prefectural University, Shobara, Japan, 2008
Post-doc, Department of Biochemistry, University of Oxford, UK, 2011-2016
Research Group Leader, Department of Ecophysiology at the MPI for Terrestrial Microbiology, since February 2017

Research Area: Bacterial Secretion Systems

Bacteria that live in contact to eukaryotic cells greatly benefit from being able to manipulate host cell behaviour. One of the most direct and elegant ways to reach this aim is the type III secretion system (T3SS), a molecular syringe also known as “injectisome”, used by gram-negative bacteria to inject effector proteins into host cells.

The T3SS is essential for virulence in many important human pathogens, including Salmonella, Shigella, and pathogenic Escherichia coli, that cause several millions of deaths per year. It is also important in hospital infections, for example by Pseudomonas aeruginosa, where presence of a functional T3SS is associated with higher mortality in animal models and increased antibiotic resistance, severe disease, and a bad prognosis in infected humans.

The type III secretion system, a conserved essential virulence factor for bacterial pathogens

Overview of the injectisome and its components (modified from Diepold & Wagner, 2014)
(A) Surface representations of 3D reconstructions of parts of the injectisome based on cryo-electron microscopy data (Schraidt & Marlovits, 2011). (B) Schematic representation of the injectisome. OM, outer membrane: IM, inner membrane.

While the translocated effector proteins vary between different bacterial species, the T3SS itself is highly conserved, which makes it an attractive target for anti-virulence therapeutics. However, although parts of the evocative “injection device” structure of the injectisome have been characterized in great detail (Fig. 1A), we know surprisingly little about the molecular function of the T3SS. How do the components of the injectisome interact to allow the fast and ordered translocation of the effectors? Which molecular events lead to effector export, and how is the energy generated?

My group wants to understand how the T3SS works on the molecular level, how it is activated and regulated during the infection process, and how we can control or inhibit its function.

To this aim, we analyze the T3SS in live bacteria, both under controlled conditions, and in contact to host cells. We apply cutting edge live-cell and superresolution microscopy, complemented by a various biochemical and genetic methods, and closely collaborate with leading researchers within and beyond the Max Planck Institute.

 

Research areas:

Investigating the molecular function of the T3SS

The regulation of the T3SS during infection

Selected publications

Rocha J, Richardson C, Zhang M, Darch C, Cai E, Diepold A & Gahlmann A (2018) Single-molecule tracking in live Yersinia enterocolitica reveals distinct cytosolic complexes of injectisome subunits. Integrative Biology 10, 502-515

Diepold A, Sezgin E, Huseyin M, Mortimer T, Eggeling C & Armitage JP. (2017) A dynamic and adaptive network of cytosolic interactions governs protein export by the T3SS injectisome, Nature Communications 8: 15940.

Morgan JM, Duncan MC, Johnson KS, Diepold A, Lam H, Dupzyk AJ, Martin LR, Wong WR, Armitage JP, Linington RG & Auerbuch V (2017) Piericidin A1 Blocks Yersinia Ysc Type III Secretion System Needle Assembly. mSphere 2: e00030-1.

Zoued A & Diepold A (2017) Defining Assembly Pathways by Fluorescence Microscopy. In Methods in molecular biology (Clifton, N.J.), Journet L & Cascales E (eds) pp 289–298. 

Diepold A, Kudryashev M, Delalez NJ, Berry RM & Armitage JP. (2015) Composition, Formation and Regulation of the Cytosolic C-ring, a Dynamic Component of the Type III Secretion Injectisome, PLOS Biology 13: e1002039.

Gerc AJ*, Diepold A*, Trunk K, Porter M, Rickman C, Armitage JP†, Stanley-Wall NR† & Coulthurst SJ. (2015) Visualization of the Serratia Type VI secretion system reveals unprovoked attacks and dynamic assembly, Cell Reports 12, 2131-2142.  (*,†: equal contribution)

Kudryashev M*, Diepold A*, Amstutz M, Armitage JP, Cornelis GR & Stahlberg H. (2015) Yersinia enterocolitica type III secretion injectisomes form regularly spaced clusters which incorporate new machines upon activation, Mol. Microbiol. 95, 875-884.  (*: equal contribution) (Cover image of Molecular Microbiology, Volume 95, Issue 5)

Diepold A & Armitage JP. (2015) Type III secretion systems – the bacterial flagellum and the injectisome, Phil Trans R Soc B 370, 20150020.

Diepold A & Wagner S. (2014) Assembly of the bacterial type III secretion machinery, FEMS Microbiol Rev 38, 802–822.

Kudryashev M, Stenta M, Schmelz S, Amstutz M, Wiesand U, Castaño-Díez D, Degiacomi MT, Münnich S, Bleck C, Kowal J, Diepold A, Heinz D, Dal Peraro M, Cornelis GR & Stahlberg H. (2013) In situ structural analysis of the Yersinia enterocolitica injectisome, eLIFE 2013;2:e00792.

Diepold A*, Wiesand U*, Amstutz M & Cornelis GR. (2012) Assembly of the Yersinia injectisome: the missing pieces, Mol. Microbiol. 85, 878-892.  (*: equal contribution) 

Diepold A, Wiesand U & Cornelis GR. (2011) The assembly of the export apparatus (YscR,S,T,U,V) of the Yersinia type III secretion apparatus occurs independently of other structural components and involves the formation of an YscV oligomer, Mol. Microbiol. 82, 502-514.

Diepold A, Amstutz M, Abel S, Sorg I, Jenal U & Cornelis GR. (2010) Deciphering the assembly of the Yersinia type III secretion injectisome, EMBO J. 29, 1928-40.


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