- vaccine design and evaluation
- pathogenesis of beta-hemolytic streptococci
- genetic and genomics of streptococci
- infections of medical devices
- molecular microbiology
- molecular epidemiology
Dr David McMillan gained his PhD in 1999 from the University of Wollongong. His postdoctoral studies were carried out as a Research Officer at the Queensland Institute of Medical Research and later an Alexander Von Humboldt Research Fellow at the Gesellschaft für Biotechnologische Forschung mbH (GBF), Braunschweig, Germany. In 2005 Dr McMillan returned to Australia as a Senior Research Officer in the Bacterial Pathogenesis Laboratory at QIMR. In 2013 he commenced as a Senior Research Fellow at the University of the Sunshine Coast and is now the Leader of the Inflammation and Healing Research Cluster.
Dr McMillan's current research interests are the β-hemolytic bacteria Streptococcus pyogenes (group A streptococcus, GAS) and S. dysgalactiae subspecies equisimilis (human group C and streptococci, SDSE). GAS associated diseases are estimated to kill 500,000 people each year. This burden of death makes GAS one of the Top Ten bacterial killers of humans. SDSE is considered an emerging pathogen with a disease spectrum similar to GAS. Changes in the disease epidemiology of GAS, and SDSE underscore the need to improve our understanding of the factors that contribute to specific disease outcomes, and to develop novel strategies that will aid in disease prevention.
Dr McMillan also has research interests in the area of bacterial colonisation and Infection of medical devices, a leading cause of hospital acquired infection. His research in this area has the aim of investigating new methods for diagnose and characterisation of bacterial colonisation of medical devices, and to develop novel technologies that reduce device colonisation.
- The role of SIC and DRS in protecting streptococci from antimicrobial peptides.
- Development of group A streptococcal vaccines.
- Genetics and genomics of Groups A and G streptococci.
- Population structure and evolution of group G streptococcus.
- Evaluation of bacterial colonisation of clinically derived catheters.
- Characterisation of bacterial community structure of clinically derived catheters.
- Evaluation of a vaccine to combat common streptococcal diseases. McMillan, D.J., N. Ketheesan, L. Hafner, M. Sanderson-Smith and K. Sriprakash. NHMRC Project grant 2012-2014
- The SAVE Trial: Securing All intraVenous devices Effectively in hospitals. A randomised controlled trial. Rickard, C., J. Fraser, J. Webster, A. Marshall, J. Young, G. Playford., D.J. McMillan, M. McGrail, J. Gowardman, O. Thom, H. Reynolds, J. Whitty, J. Crilly, K. Dunster, N. Marsh, N, S. Keogh, L. Zhang. NHMRC Project Grant. 2013-2016
- Intravascular device administration sets: Replacement after Standard Versus Prolonged use (The RSVP Trial). Rickard C., M. Wallis, J. Young, J. Gowardman, M. Whitby, D.J. McMillan, J. Fraser, and L. Zhang. NHMRC Project grant (APP1008428). 2011-2014
Bauer MJ, Georgousakis MM, Vu T, Henningham A, Hofmann A, Rettel M, Hafner LM, Sriprakash KS, McMillan DJ. 2012. Evaluation of novel Streptococcuspyogenesvaccine candidates incorporating multiple conserved sequences from the C-repeat region of the M-protein.Vaccine 30:2197-2205.
Smeesters PR, McMillan DJ, Sriprakash KS. 2010. The streptococcal M protein: a highly versatile molecule. Trends Microbiol 18:275-282.
McMillan DJ, Bessen DE, Pinho M, Ford C, Hall GS, Melo-Cristino J, Ramirez M. 2010. Population genetics ofStreptococcus dysgalactiaesubspeciesequisimilisreveals widely dispersed clones and extensive recombination.PLoS One 5:e11741.
Chhatwal GS, McMillan DJ, Talay SR. 2006. Pathogenicity Factors in Group C and G Streptococci, p. 213-221.In Fischetti VA, Novick RP, Ferretti JJ, Portnoy DA, Rood JI (ed.), Gram-positive pathogens, 2 ed. ASM Press, Washington D. C.
McMillan DJ, Beiko RG, Geffers R, Buer J, Schouls LM, Vlaminckx BJ, Wannet WJ, Sriprakash KS, Chhatwal GS. 2006. Genes for the majority of group A streptococcal virulence factors and extracellular surface proteins do not confer an increased propensity to cause invasive disease. Clin Infect Dis 43:884-891.
Sanderson-Smith M, De Oliveira DM, Guglielmini J, McMillan DJ, Vu T, Holien JK, Henningham A, Steer AC, Bessen DE, Dale JB, Curtis N, Beall BW, Walker MJ, Parker MW, Carapetis JR, Van Melderen L, Sriprakash KS, Smeesters PR; the M Protein Study Group. A systematic and functional classification of Streptococcus pyogenes that serves as a new tool for molecular typing and vaccine development. J Infect Dis. 2014
Smyth D, Cameron A, Davies MR, McNeilly C, Hafner L, Sriprakash KS, McMillan DJ. DrsG from Streptococcus dysgalactiae subsp. equisimilis Inhibits the Antimicrobial Peptide LL-37. Infect Immun. 2014 Jun;82(6):2337-44.
Potential research projects for HDR and Honours students
Development of polyvalent vaccines for prevention of infection with group A streptococcus.
Infection with group A streptococcus (GAS) is estimated to kill half a million people each year. The prevalence of these diseases is particularly high in Australia’s Indigenous population. This project will use a combination of molecular epidemiology, immunology and bioinformatics to design and produce novel group A streptococcal vaccine candidates. The effectiveness of these candidates to induce immune responses that kill GAS will then be investigated.
Functional characterisation of SIC, a streptococcal protein that inhibit the host innate immune system.
Antimicrobial peptides (AMPs) are small molecules produced by immune system that act as front-line defenders against bacterial infection. GAS produces a protein (SIC) that inhibit the anti-bacterial activity of this AMPs. We have recently shown SIC to possess amino acid motif that is associated with protein-protein interactions. The aim of this project is to determine whether this motif is responsible for the AMP inhibitory properties of SIC.
Characterisation of the function of the M-protein in SDSE.
The M-protein is the major virulence factor of GAS, and also present, in the related Streptococcus dysgalactiae subsp equisimilis (SDSE). However the role this protein plays in the virulence of SDSE has not been characterised. The aim of this project is to (i) demonstrate the M-protein is expressed on the surface of SDSE, (ii) identify host ligands of the protein and (iii) characterise the role to the SDSE M-protein in the persistence of SDSE.
Identification and Characterisation of novel antimicrobials targeting the ESKAPE pathogens.
The emergence of antimicrobial resistance is a major global issue in human health. For several pathogens, isolates have emerged for which no antibiotic is available. Antibiotic resistance organisms are of particular concern in hospitals and other clinical settings. The major antibiotic resistant organisms associated with nosocomial infection are called ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp.). The goal of this research project is to identify and characterise antimicrobial compounds in Australian eucalypt species. The project will involve extraction of plant samples, antimicrobial screening and characertisation of isolate compounds
Characterisation of bacteria colonising medical devices. Catheter are the leading cause of hospital bacterial infections. The major aim of projects in this area is to genetically and phenotypically characterise bacterial isolates associated with colonisation of catheters. The project will involves techniques such as PCR, DNA sequencing, biofilm characterisation and other phenotypic assays.