Translational Microbiology
Discovering better ways to detect and prevent diseases caused by bacterial pathogens of major global health importance.
Our focus is on bacterial pathogens of major global health importance, including Streptococcus pneumoniae (the pneumococcus) and Streptococcus pyogenes (group A streptococcus, Strep A).
Our focus
- Investigating how infections can be best diagnosed and prevented with vaccines
- Discovering how these pathogens colonise, transmit and cause disease, including their interaction with other microbes
- Collaboration closely with clinicians, epidemiologists and immunologists, including in countries in the Asia-Pacific region, to facilitate translation and global impact
Our research areas
Improve vaccine strategies in low-middle-income settings by identifying:
- Impact of vaccines in children and adults
- Optimal vaccination schedules
- Vaccine impact on antimicrobial resistance
- Improved vaccine strategies in humanitarian crisis settings
- Burden of pneumococcal disease in the Asia-Pacific
Better diagnostics and disease surveillance using molecular microbiology:
- Developing diagnostics for children with severe pneumonia
- Discovery of new serotypes and variants to inform vaccine and surveillance strategies
- Using genomics to understand antimicrobial resistance and the pneumococcal population structure
Understanding the biology of bacterial pathogens and using laboratory and animal models to answer key questions for:
- Bacterial-viral interactions
- Bacterial colonisation and carriage
- Bacterial transmission and disease
Our projects
Improved diagnostics for serious childhood pneumonia
MATE & MATE-Asia
Empyema is an increasingly common complication of severe pneumonia in children living in Australia and around the world. Identifying the bacterial species responsible for empyema helps doctors prescribe the best course of antibiotics. With current methods, the bacterial cause is identified in about 20 per cent of cases. In the Molecular Assessment of Thoracic Empyema (MATE) and MATE-Asia studies, we are developing a new molecular diagnostic to improve identification rates for children with empyema and therefore improve patient outcomes. These studies will also help us understand the burden of pneumococcal and other bacterial infections to inform vaccine strategies in Australia and the wider Asia-Pacific Region.
Vaccine strategies for low-middle-income countries
Vaccine impact studies
Introducing pneumococcal conjugate vaccines (PCV) results in a dramatic reduction in pneumococcal diseases such as pneumonia. PCVs also reduce colonisation (carriage) of the pneumococci included in the vaccine, preventing progression to disease and the spread to others (herd protection). Using microbiological techniques, we are measuring the impact of PCV on pneumococcal nasopharyngeal carriage in children and/or adults in Fiji, Mongolia, Lao and Papua New Guinea.
Vaccine trials
Despite the dramatic reduction in pneumococcal disease following vaccine introduction, there is little evidence to guide decision-makers on which vaccine to choose. The high price of pneumococcal vaccines remains a significant barrier to implementation in many countries. We are using microbiology to assess differences in licensed vaccines and examine the effect of different schedules with fewer doses. These trials are being conducted in Ho Chi Minh City and Nha Trang to assess the impact on nasopharyngeal carriage, and therefore, likely herd protection.
Novel approaches to prevent disease
Preventing Young Infant Infections using Azithromycin in Labour
Skin and soft tissue infections (SSTIs) are common causes of infant and maternal morbidity (illness) and infant mortality (death). A simple, low-cost approach to preventing these infections is required in settings where access to health care is poor, and where other approaches are unsuitable. In the Bulabula MaPei project we are investigating whether a single dose of oral azithromycin given to women in labour in Fiji reduces young infant SSTI rates and carriage of bacteria commonly causing maternal and infant infections.
Pneumococcal carriage following vaccine introduction
Use of genomics to determine the effect of vaccine introduction on pneumococcal antimicrobial resistance
The serotypes contained within PCV are those which have more antimicrobial resistance (AMR). Vaccine introduction reduces the carriage of PCV serotypes and limits the use of antibiotics by preventing pneumococcal infections. Our aim is to determine the effectiveness of PCV13 against pneumococcal AMR in Lao and other settings.
Identify emerging non-vaccine serotypes
There are 100 serotypes of S. pneumoniae. The current pneumococcal vaccines protect against 10 or 13 serotypes. Following PCV introduction, non-vaccine types become more common (serotype replacement) in both carriage and disease. We are developing new molecular techniques to determine which serotypes are causing severe pneumonia in children across Asia and monitoring serotype replacement as part of our vaccine impact studies. We are using genomics to understand what subtypes (genetic lineages) may emerge in the post-PCV era to understand and address emerging future vaccination challenges.
Discovery of novel serotype variants
We are discovering and characterising novel genetic variants (and potentially new serotypes) in low and middle-income countries across the Asia-Pacific. Specifically, our work aims to understand how these variants can be mistyped using common methods used in carriage studies and disease surveillance programs, and whether they would be targeted by existing vaccines, to inform future vaccine strategies.
NHMRC Centre of Research Excellence (CRE) for Pneumococcal Disease Control in the Asia-Pacific
Our group is leading several microbiology projects within the CRE. The CRE aims to address two outstanding research gaps for pneumococcal conjugate vaccine (PCV) use in the Asia-Pacific region:
- Country decisions regarding reduced dose PCV schedules (1+1)
- Understanding serotype replacement following vaccine introduction
The program will generate new evidence to support decisions regarding the sustainability of national immunisation PCV programs, forge partnerships with key end-users, establish new international linkages to enable broader dissemination, develop the next generation of nationally competitive researchers.
Interactions of respiratory bacteria and viruses
Interactions between pneumococcus and viruses
The contribution of bacterial-viral co-infections to the onset and severity of disease is increasingly attracting global interest. Co-infections of Streptococcus pneumoniae with respiratory viruses (e.g. influenza or Respiratory Syncytial Virus) impact the severity of acute respiratory infections. We aim to explain the interplay between pneumococci and respiratory viruses, understand the mechanisms involved and the implications and applications of these interactions for vaccines.
Group A streptococcus and viral interactions
The bacterium Streptococcus pyogenes (group A streptococcus, GAS or Strep A) causes a range of mild to severe infections, from sore throat to toxic shock syndrome. There is recent clinical epidemiological evidence that viruses are important in GAS pathogenesis, but little is known about this process. We are using murine and specialised cell-culture models to examine the effect of viruses on S. pyogenes colonisation, transmission (spread), disease and the mechanisms involved.Funding
- Bill and Melinda Gates Foundation
- GAVI The Vaccine Alliance
- National Health and Medical Research Council
- Wellcome Trust
- Pfizer
- Research for Health in Humanitarian Crises
- Murdoch Children’s Research Institute
- ISPPD – Robert Austrian Awards in Pneumococcal Vaccinology
- Jack Brockhoff Foundation
- MSD Pneumococcus Investigator Studies Program (MISP)
- Thrasher Research Fund
Collaborations
Australian collaborators
- The Royal Children’s Hospital (Centre for International Child Health (CICH))
- The University of Melbourne Department of Paediatrics and Department of Microbiology and Immunology
- Monash Children's Hospital
- Department of Paediatrics, Monash University
- RMIT University
- La Trobe University
- Menzies School of Health Research
- Telethon Kids Institute
- The South Australian Health and Medical Research Institute (SAHMRI)
- QIMR Berghofer Medical Research Institute
International collaborators
- Colonial War Memorial Hospital, Fiji
- The Fiji Ministry of Health and Medical Services
- The Mongolian Ministry of Health
- National Center of Communicable Diseases (NCCD), Mongolia
- Pasteur Institute, Vietnam
- St George’s University of London (SGUL), UK
- Laos-Oxford-Mahosot Welcome Research Unit (LOMWRU)
- Papua New Guinea Institute of Medical Research
- London School of Hygiene and Tropical Medicine
- Public Health England
- Eijkman Institute, Indonesia
- Universitas Padjadjaran/Hasan Sadikin General Hospital - Department of Child Health, Indonesia
- University of Bern, Switzerland
- Philippine General Hospital, University of the Philippines
- Duke-National University of Singapore, Singapore
- Siriraj Hospital, Mahidol University, Bangkok, Thailand
- Boston Children’s Hospital
- Yale School of Public Health
- Wellcome Sanger Institute, UK
Featured publications
Satzke C, Turner P, Virolainen-Julkunen A, Adrian PV, Antonio M, Hare KM, Henao-Restrepo AM, Leach AJ, Klugman KP, Porter BD, Sá-Leão R, Scott JA, Nohynek H, O'Brien KL; WHO Pneumococcal Carriage Working Group. Standard method for detecting upper respiratory carriage of Streptococcus pneumoniae: updated recommendations from the World Health Organization Pneumococcal Carriage Working Group. Vaccine. 2013 Dec 17;32(1):165-79. doi: 10.1016/j.vaccine.2013.08.062.
Satzke C, Dunne EM, Porter BD, Klugman KP, Mulholland EK; PneuCarriage project group. The PneuCarriage Project: A Multi-Centre Comparative Study to Identify the Best Serotyping Methods for Examining Pneumococcal Carriage in Vaccine Evaluation Studies. PLoS Med. 2015 Nov 17;12(11):e1001903; discussion e1001903. doi: 10.1371/journal.pmed.1001903.
Dunne EM, Satzke C, Ratu FT, Neal EFG, Boelsen LK, Matanitobua S, Pell CL, Nation ML, Ortika BD, Reyburn R, Jenkins K, Nguyen C, Gould K, Hinds J, Tikoduadua L, Kado J, Rafai E, Kama M, Mulholland EK, Russell FM. Effect of ten-valent pneumococcal conjugate vaccine introduction on pneumococcal carriage in Fiji: results from four annual cross-sectional carriage surveys. Lancet Glob Health. 2018 Dec;6(12):e1375-e1385. doi: 10.1016/S2214-109X(18)30383-8.
Boelsen LK, Dunne EM, Mika M, Eggers S, Nguyen CD, Ratu FT, Russell FM, Mulholland EK, Hilty M, Satzke C. The association between pneumococcal vaccination, ethnicity, and the nasopharyngeal microbiota of children in Fiji. Microbiome. 2019 Jul 16;7(1):106. doi: 10.1186/s40168-019-0716-4.
Temple B, Tran HP, Dai VTT, Smith-Vaughan H; VPT-II Collaborator Group; Licciardi PV, Satzke C, Nguyen TV, Mulholland K. Efficacy against pneumococcal carriage and the immunogenicity of reduced-dose (0 + 1 and 1 + 1) PCV10 and PCV13 schedules in Ho Chi Minh City, Viet Nam: a parallel, single-blind, randomised controlled trial. Lancet Infect Dis. 2023 Aug;23(8):933-944. doi: 10.1016/S1473-3099(23)00061-0. Epub 2023 Apr 14.