Associate Professor Thomas Kurt Proft

MSc, PhD

Biography

  • 1991: MSc in Biology, University of Heidelberg, Germany
  • 1995: PhD (Dr. rer.nat.) in Molecular Microbiology, Center for Molecular Biology Heidelberg, University of Heidelberg, Germany
  • 1995-2001: Research Fellow, University of Auckland
  • 2001-2007: Senior Research Fellow, University of Auckland
  • 2004-2008: Hercus Senior Research Fellow (HRC New Zealand)
  • 2007-2011: Senior Lecturer in Microbiology and Infectious Diseases, University of Auckland

Research | Current

Streptococcus pyogenes, or group A streptococcus (GAS) can cause a variety of diseases ranging from pharyngitis and tonsillitis to severe invasive diseases, such as bacteremia, septic scarlet fever, necrotizing fasciitis (“flesh eating disease”) and streptococcal toxic shock syndrome (STSS). Streptococcal sequela, which include glomerulonephritis and acute rheumatic fever are often complications of streptococcal infection and this remains a significant problem in developed countries. GAS infections, including skin and soft tissue infections, are believed to account for >10 million cases each year in the U.S. alone. In 2002, the Centers for Disease Control and Prevention estimated that there were 9000 cases of invasive GAS disease (3.2/100,000 population) and 1200 GAS-associated deaths in the U.S. Acute rheumatic fever (ARF) continues to produce significant cardiac morbidity and mortality in young people in the developing world, where it remains the leading cause of acquired heart disease. Streptococcal infections affect New Zealanders of all ethnicities. However, ethnic inequalities exist in morbidity and mortality resulting from GAS infection. Maori and Pacific Islanders have disproportionally high hospital admissions for streptococcal skin diseases, necrotising fasciitis, and acute rheumatic fever. Our research focuses on virulence factors produced by GAS, in particular superantigens and cell wall-anchored virulence factors, such as pili, and the development of a vaccine against GAS.

 

 Streptococcus pyogenes nuclease (SpnA) and streptococcus 5'-nucleotidase (S5nA)

SpnA is a cell wall-anchored nuclease that cleaves ssDNA, dsDNA and RNA. We have shown that SpnA is able to degrade neutrophil extracellular traps (NETs) to evade the host immune response. Our work focuses on further biochemical and structural characterisation of this enzyme and investigate its potential as a vaccine target and diagnostic tool. S5nA is a cell wall-anchored nucleotidase that converts nucleotides into nucleosides and inorganic phosphate. Of particular interest is the hydrolysis of AMP and dAMP into the immunomodulatory components adenosine and deoxyadenosine, respectively. Our current research focuses on the biochemical and structural characterisation of S5nA, in particular a possible synergy with SpnA to generate the macrophage-toxic dAdo from degraded NETs.  

 

A pilus-based vaccine against GAS

Pili are thin, hair-like structures protruding from the bacterial cell surface and are involved in host cell adhesion and biofilm formation. Currently, 6 different pilus types have been identified in GAS. We are interested in pilus function, in particular the M2 pilus type which displays a unique immune evasion property, and in expoling the use of this structure as a target for a vaccine against GAS.  

 

Biophotonic imaging of GAS

We have developed a plasmid-based system for the bioluminescence labeling of GAS and related species with firefly luciferase and Lux. Expression of the reporter genes from a plasmid results in strong bioluminescence signals with detection limits of around 50 cfu on a plate reader. The introduction of a toxin-antitoxin cassette into the plasmid ensures segregational stability in the absence of an antibiotic making this system ideal for animal infection studies. Furthermore, the plasmid can easily be introduced in any GAS strain and we already have labelled more than 70 clinical isolates.

 

Current lab members:

Dr. Jacelyn Loh: Heart Foundation Research Fellow

Dr. Catherine Tsai: Research Fellow

Mrs. Adrina Khemlani: Research Technician

Ms. Kar Yan Soh: PhD student

Mr. Sam Blanchett: PhD student

Ms. Haniyeh Aghababa: PhD student

Mr. Callum Chalmers: MSc student

Ms. Kim Paras: BSc Hon student

 

Teaching | Current

MEDSCI 202: Microbiology and Immunology  (Course Director)

MEDSCI 203: Mechanisms of Disease

NURSING 201: Microbiology and Immunology

MEDSCI 301: Molecular Basis of Disease

MEDSCI 314: Immunology

BIOSCI 349: Biomedical Microbiology

MBChB 321: Blood, Immunity and Infection

MEDSCI 705: Infection, Immunity and Disease

MEDSCI 708: Advanced Immunology

 

Postgraduate supervision

 

 

Distinctions/Honours

  • Young Investigator Travel Award, Japanese Society for Immunology (2000)
  • Early Career Research Excellence Award, University of Auckland (2001)
  • Invitrogen Life Sciences Young Investigator Award (2004)
  • HRC Sir Charles Hercus Research Fellowship (2004-2008)

Areas of expertise

Group A Streptococcus

Bacterial virulence

Streptococcal pili

Superantigens

Bacterial Toxins

Bacterial Immune Evasion

Microbial Genomics

Group A Streptococcus vaccine

 

Committees/Professional groups/Services

Faculty Board of Research (FMHS)

Research Committee (Dept. of Molecular Medicine & Pathology)

Editorial Board - Biotechnology Letters

Editorial Board - World Journal of Biological Chemistry

Selected publications and creative works (Research Outputs)

  • Loh, J. M. S., Tsai, J.-Y. C., & Proft, T. (2017). The ability of Group A streptococcus to adhere to immortalized human skin versus throat cell lines does not reflect their predicted tissue tropism. Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases, 23 (9), 677.e1-677.e3. 10.1016/j.cmi.2017.03.011
    Other University of Auckland co-authors: Jacelyn Loh, Catherine Tsai
  • Loh, J. M. S., Lorenz, N., Tsai, C. J.-Y., Khemlani, A. H. J., & Proft, T. (2017). Mucosal vaccination with pili from Group A Streptococcus expressed on Lactococcus lactis generates protective immune responses. Scientific reports, 7 (1)10.1038/s41598-017-07602-0
    Other University of Auckland co-authors: Jacelyn Loh, Catherine Tsai
  • Lorenz, N., Loh, J. M. S., Moreland, N. J., & Proft, T. (2017). Development of a high-throughput opsonophagocytic assay for the determination of functional antibody activity against Streptococcus pyogenes using bioluminescence. Journal of Microbiological Methods, 134, 58-61. 10.1016/j.mimet.2017.01.010
    Other University of Auckland co-authors: Jacelyn Loh, Nikki Moreland
  • Hanson-Manful, P., Whitcombe, A. L., Young, P. G., Atatoa Carr, P. E., Bell, A., Didsbury, A., ... Moreland, N. J. (2017). The novel Group A Streptococcus antigen SpnA combined with bead-based immunoassay technology improves streptococcal serology for the diagnosis of acute rheumatic fever. Journal of Infection10.1016/j.jinf.2017.12.008
    Other University of Auckland co-authors: Paul Young, Edwin Mitchell, Rod Dunbar, Nikki Moreland
  • Tsai, J.-Y. C., Loh, J. M. S., Clow, F., Lorenz, N., & Proft, T. (2017). The Group A Streptococcus serotype M2 pilus plays a role in host cell adhesion and immune evasion. Molecular Microbiology, 103 (2), 282-298. 10.1111/mmi.13556
    Other University of Auckland co-authors: Catherine Tsai, Jacelyn Loh
  • Raynes, J. M., Frost, H. R. C., Williamson, D. A., Young, P. G., Baker, E. N., Steemson, J. D., ... Atatoa Carr, P. E. (2016). Serological Evidence of Immune Priming by Group A Streptococci in Patients with Acute Rheumatic Fever. Frontiers in Microbiology, 7, 1-6. 10.3389/fmicb.2016.01119
    URL: http://hdl.handle.net/2292/30468
    Other University of Auckland co-authors: Edward Baker, Nikki Moreland, Paul Young, Rod Dunbar, Jacelyn Loh, Jeremy Raynes
  • Tsai, C. J., Loh, J. M., & Proft, T. (2016). Galleria mellonella infection models for the study of bacterial diseases and for antimicrobial drug testing. Virulence, 7 (3), 214-229. 10.1080/21505594.2015.1135289
    URL: http://hdl.handle.net/2292/29410
    Other University of Auckland co-authors: Jacelyn Loh, Catherine Tsai
  • Proft, T., & Fraser, J. D. (2016). Streptococcal Superantigens: Biological properties and potential role in disease. In J. J. Ferretti, D. L. Stevens, V. A. Fischetti (Eds.) Streptococcus Pyogenes: Basic Biology to Clinical Manifestations (pp. 333-350). Oklahoma, USA: The University of Oklahoma Health Sciences Center. Related URL.
    URL: http://hdl.handle.net/2292/28349
    Other University of Auckland co-authors: John Fraser

Identifiers

Contact details

Primary location

M&HS BUILDING 502 - Bldg 502
Level 3, Room 301
85 PARK RD
GRAFTON
AUCKLAND 1023
New Zealand

Web links