Leyton Group - Assembly, function, and applications of nanoscale bacterial surface structures

Autotransporters are a large family of virulence proteins produced by Gram-negative bacterial pathogens responsible for infectious diseases such as diarrhoea, whooping cough, cholera, chlamydia, and bacterial meningitis. Autotransporters help establish infection and contribute to disease by performing a vast array of effector functions, including adhesion and invasion of, and cytotoxicity towards eukaryotic host cells, biofilm formation, and disruption of the host immune system. Our research is focused on understanding how autotransporters are assembled into bacterial outer membranes, and how they function to mediate infection and disease once they get there. We are also interested in reengineering autotransporters as recombinant protein production devices for use in basic research, biotechnology, or pharmaceutical applications.

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Selected publications

  • Xiaojun Yuan, Matthew D. Johnson, Jing Zhang, Alvin W. Lo, Mark A. Schembri, Lakshmi C. Wijeyewickrema, Robert N. Pike, Gerard H. M. Huysmans, Ian R. Henderson & Denisse L. Leyton (2018). Molecular basis for the folding of B-helical autotransporter passendger domains. Nature Communications 9:1395  doi: 10.1038/ s41467-018-03593-2
  • Drobnak I, Braselmann E, Chaney JL, Leyton DL, Bernstein HD, Lithgow T, Luirink J, Nataro JP, Clark PL (2014). Of linkers and autochaperones: An unambiguous nomenclature to identify common and uncommon themes for autotransporter secretion. Molecular Microbiology doi: 10.1111/mmi.12838.
  • Shen HH, Leyton DL, Shiota T, Belousoff MJ, Noinaj N, Lu J, Holt SA, Tan K, Selkrig J, Webb CT, Buchanan SK, Martin LL and Lithgow T (2014). Reconstitution of a nanomachine driving the assembly of proteins into bacterial outer membranes. Nature Communications 5:5078. doi: 10.1038/ncomms6078.
  • Leyton DL, Johnson MD, Thapa R, Huysmans GHM, Dunstan RA, Celik N, Shen H, Loo D, Belousoff MJ, Purcell AW, Henderson IR, Beddoe T, Rossjohn J, Martin LL, Strugnell RA, Lithgow T (2014). A mortise-tenon joint in the transmembrane domain modulates autotransporter assembly into bacterial outer membranes. Nature Communications 5:4239. doi: 10.1038/ncomms5239.
  • Selkrig J, Leyton DL, Webb CT, Lithgow T (2013). Assembly of β-barrel proteins into bacterial outer membranes. Biochimica et Biophysica Acta-Molecular Cell Research pii: S0167-4889(13)00354-6. doi: 10.1016/j.bbamcr.2013.10. 009.
  • Celik N, Webb CT, Leyton DL, Holt KE, Heinz E, Gorrell R, Kwok T, Naderer T, Strugnell RA, Speed TP, Teasdale RD, Likic VA, Lithgow T (2012). A bioinformatic strategy for the detection, classification and analysis of bacterial autotransporters. PLoS One 7(8):e43245. doi: 10.1371/journal.pone.0043245.
  • Sevastsyanovich YR, Leyton DL, Wells TJ, Wardius CA, Tveen-Jensen K, Morris FC, Knowles TJ, Cunningham AF, Cole JA, Henderson IR (2012). A generalised module for the selective extracellular accumulation of recombinant proteins. Microbial Cell Factories 11:69. doi: 10.1186/1475-2859-11-69.
  • Selkrig J, Mosbahi K, Webb CT, Belousoff MJ, Perry AJ, Wells TJ, Morris FC, Leyton DL, Totsika M, Phan M, Celik N, Kelly M, Oates C, Hartland EL, Robins-Browne RM, Harsha Ramarathinam S, Purcell AW, Schembri MA, Strugnell RA, Henderson IR, Walker D, Lithgow T (2012). Discovery of an archetypal protein transport system in bacterial outer membranes. Nature Structural & Molecular Biology Apr 1. doi: 10.1038/nsmb.2261.
  • Leyton DL, Rossiter AE, Henderson IR (2012). From self sufficiency to dependence: mechanisms and factors important for autotransporter biogenesis. Nature Reviews Microbiology 10; 213-25.
  • Leyton DL, Sevastsyanovich YR, Browning DF, Rossiter AE, Wells TJ, Fitzpatrick RE, Overduin M, Cunningham AF, Henderson IR (2011). Size and conformation limits to secretion of disulfide-bonded loops in autotransporter proteins. Journal of Biological Chemistry 286; 42283-91.
  • Raghunathan D, Wells TJ, Morris FC, Shaw RK, Bobat S, Peters SE, Paterson GK, Jensen KT, Leyton DL, Blair JM, Browning DF, Pravin J, Flores-Langarica A, Hitchcock JR, Moraes CT, Piazza RM, Maskell DJ, Webber MA, May RC, MacLennan CA, Piddock LJ, Cunningham AF, Henderson IR (2011). SadA, a trimeric autotransporter from Salmonella enterica serovar Typhimurium, can promote biofilm formation and provides limited protection against infection. Infection and Immunity 79; 4342-52.
  • Rossiter AE*, Leyton DL*, Tveen-Jensen K, Browning DF, Sevastsyanovich Y, Knowles TJ, Nichols KB, Cunningham AF, Overduin M, Schembri MA, Henderson IR (2011). The essential β-barrel assembly machinery complex components BamD and BamA are required for autotransporter biogenesis. Journal of Bacteriology 193; 4250-3. *these authors contributed equally  
  • Rossiter AE, Browning DF, Leyton DL, Johnson MD, Godfrey RE, Wardius CA, Desvaux M, Cunningham AF, Ruiz-Perez F, Nataro JP, Busby SJ, Henderson IR (2011). Transcription of the plasmid-encoded toxin gene from enteroaggregative Escherichia coli is regulated by a novel co-activation mechanism involving CRP and Fis. Molecular Microbiology 81:179-91.
  • Knowles TJ, Browning DF, Jeeves M, Maderbocus R, Rajesh S, Sridhar P, Manoli E, Emery D, Sommer U, Spencer A, Leyton DL, Squire D, Chaudhuri RR, Viant M, Cunningham AF, Henderson IR and Overduin M (2011). Structure and function of BamE within the outer membrane and the β-barrel assembly machine. EMBO Reports 12; 123-128.
  • Tsai JC, Yen M, Castillo R, Leyton DL, Henderson IR and Saier, Jr. MH (2010). Phylogenetic analyses reveal the Bacterial Intimins and Invasins are a large and novel family of secreted proteins. PLoS One, 5; e14403.
  • Leyton DL, Luna MG, Sevastsyanovich YR, Jensen KT, Browning DF, Scott-Tucker A and Henderson IR (2010). The unusual extended signal peptide region is not required for secretion and function of an Escherichia coli autotransporter. FEMS Microbiology Letters 311: 133-139.  
  • Chaudhuri RR, Sebaihia M, Hobman JL, Webber MA, Leyton DL, Goldberg MD, Cunningham AF, Scott-Tucker A, Ferguson PR, Thomas CM, Frankel G, Tang CM, Dudley EG, Roberts IS, Rasko DA, Pallen MJ, Parkhill J, Nataro JP, Thomson NR and Henderson IR (2010). Complete Genome Sequence and Comparative Metabolic Profiling of the Prototypical Enteroaggregative Escherichia coli Strain 042. PLoS One, 5; e8801.
  • Ruiz-Perez F, Henderson IR, Leyton DL, Rossiter AE, Zhang Y and Nataro JP (2009). Roles of periplasmic chaperone proteins in the biogenesis of serine protease autotransporters of Enterobacteriaceae. Journal of Bacteriology 191; 6571-6583.
  • Leyton DL, Adams LM, Kelly M, Sloan J, Tauschek M, Robins-Browne RM and Hartland EL (2007). Contribution of a novel gene rpeA encoding a putative autotransporter adhesin to intestinal colonization by rabbit enteropathogenic Escherichia coli. Infection and Immunity 75; 4664-4669.
  • Leyton DL, Sloan J, Hill RE, Doughty S and Hartland EL (2003). Transfer region of pO113 from enterohemorrhagic Escherichia coli: Similarity with R64 and Identification of a novel plasmid-encoded autotransporter, EpeA. Infection and Immunity 71; 6307-6319.

All publications

Go to a complete list of publications on the ISI website.

Future Fellowships awarded to ANU big thinkers

Story | Wednesday 16 December 2015
The Australian National University (ANU) has secured five prestigious Future Fellowships, two of which have been awarded to researchers in the Research School of Biology.

ARC Discovery projects and DECRA fellowships

Story | Monday 2 November 2015

Two new Group Leaders join RSB

Story | Monday 2 February 2015
The Research School of Biology welcomes two new Group Leaders, Denisse Leyton and Guillaume Tcherkez.

Denisse Leyton

Story | Friday 30 January 2015

I feel incredibly privileged to be in the position where I am able to ask and then address the questions that drive my curiosity and re

BSB PhD Exit Seminar: Structural and functional characterisation of MlaD from Acinetobacter baumannii

Event | Thu 1 June 2023
Acinetobacter baumannii (Ab) is a clinically important pathogen that has rapidly developed resistance to many antimicrobials.

BSB PhD Exit Seminar: The loopy nature of autotransporter passenger domain folding

Event | Thu 25 May 2023
Autotransporters are a large family of bacterial secreted and/or outer membrane proteins that play key roles in the pathogenesis of many infectious diseases.
Recorded BSB Seminar - Simone Babij

BSB MPhil Exit Seminar: Understanding patterns of collateral sensitivity in the malaria parasite

Event | Thu 15 September 2022
Malaria kills around 400,000 people each year and the prevention and treatment of this disease is highly reliant on chemotherapy.
Dr Diana Stojanovski, University of Melbourne

Mitochondrial Protein Import in Health and Disease

Event | Thu 17 October 2019
Mitochondrial function and cell viability require a functional and healthy mitochondrial proteome.

Engineering alpha-1 antitrypsin for augmentation therapy

Event | Tue 28 May 2019

α-1 antitrypsin (AAT) is used as augmentation therapy in patients with AAT deficiency (AATD)-related emphysema, and is a promising therapeutic for

G protein-coupled receptors: the structural basis for their pharmacology

Event | Thu 6 December 2018

G protein-coupled receptors (GPCRs) activate intracellular signalling proteins (G proteins and arrestins) in response to extracellular signalling m