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. Māori 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.  

 

PilVax – a novel peptide delivery platform for the development of mucosal vaccines

Peptide vaccines are an attractive strategy to engineer the induction of highly targeted immune responses and avoid potentially allergenic and/or reactogenic protein regions. However, peptides by themselves are often unstable and poorly immunogenic, necessitating the need for an adjuvant and a specialised delivery system. We have developed a novel peptide delivery platform (PilVax) that allows the presentation of a stabilised and highly amplified peptide as part of the group A streptococcus serotype M1 pilus structure (PilM1) on the surface of the non-pathogenic bacterium Lactococcus lactis. To show proof of concept, we have successfully inserted the model peptide Ova324-339 into 3 different loop regions of the backbone protein Spy0128, which resulted in the assembly of the pilus containing large numbers of peptide on the surface of L. lactis. Intranasal immunisation of mice with L. lactis PilM1-Ova generated measurable Ova-specific systemic and mucosal responses (IgA and IgG). Furthermore, we show that multiple peptides can be inserted into the PilVax platform and that peptides can also be incorporated into structurally similar, but antigenically different pilus structures. PilVax may be useful as a cost-effective platform for the development of peptide-vaccines against a variety of important human pathogens.

 

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: Senior Research Fellow and 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

 

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

 

 

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

 

Selected publications and creative works (Research Outputs)

Identifiers

Contact details

Primary office location

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

Web links