Antimicrobial-resistant bacterial pathogens
Antimicrobial resistance has been highlighted by the world health organisation (WHO) and the Centres for Disease Control in the USA as one of the major public health threats of our time. Ben’s group, which is co-located with the state-wide public health and reference laboratory MDU PHL), uses epidemiology and bacterial genomics to understand the characteristics and spread of antimicrobial-resistant pathogens in hospitals and the community. Recent examples include the investigation of an outbreak of CTX-M 15 producing multi-drug resistant ST131 E. coli, locally acquired azithromycin-resistant Shigella flexneri infections, KPC producing K. pneumoniae, and drug-resistant Neisseria gonorrhoeae.
Staphylococcus aureus and Enterococcus faecium are two major opportunistic human pathogens. Staphylococcus aureus causes a wide range of hospital and community-acquired infections. The mortality rate for serious Staphylococcus aureus infection, particularly methicillin resistant Staphylococcus aureus (MRSA) is high (20–30% of bacteraemia), and the social and financial burden of Staphylococcus aureus-related disease in Australia and worldwide is becoming increasingly significant. Enterococci are members of the gastrointestinal microbiota but they have also emerged as a major cause of healthcare associated infections, accounting for approximately 10% of human cases of bacteraemia. Enterococcus faecium (Efm) and Enterococcus faecalis are the two enterococci that most frequently cause human infections, with resistance to the last-line antibiotic vancomycin becoming common in Enterococcus faecium (VREfm) in the past two decades. Tim’s group is investigating the molecular basis for increasing resistance to antibiotics and also the cleaning agents commonly used to disinfect health care facilities.
Tuberculosis (TB) and Buruli ulcer (BU) are distinct but serious diseases caused by infection with Mycobacterium tuberculosis and Mycobacterium ulcerans respectively. TB causes hundreds of thousands of deaths each year and millions of people are infected worldwide. The emergence of multi-drug resistant strains is a major concern. Tim’s group is using the power of genomics to better understand how Mycobacterium tuberculosis causes disease and to use that information to help develop an effective vaccine. BU is a neglected disease and each year, 5000 to 6000 cases are reported from 33 countries across the globe, predominantly from rural regions in West and Central Africa. The disease involves subcutaneous tissue and has several manifestations but necrotic skin ulcers are a common presentation, caused by the proliferation of bacteria beneath the dermis and a secreted bioactive bacterial lipid toxin called mycolactone. Employing genomics, Tim’s group has been at the forefront of describing the biosynthesis and role of mycolactone but the role of this molecule in the natural ecology of Mycobacterium ulcerans is not understood. Epidemiological studies frequently link BU occurrence with low-lying and wetland areas, and human-to-human transmission is rare, suggesting an environmental source of the mycobacterium. Despite more than 70 years of research, the environmental reservoir(s) and mode(s) of transmission of Mycobacterium ulcerans remain unknown. Tim’s group’s research aims to address these key questions.
Tim is leading a major project in collaboration with the Department of Health and Human Services, Barwon Health, Austin Health, CSIRO, Agriculture Victoria, the University of Melbourne and Mornington Peninsula Shire to understand how Buruli ulcer is spread and to indentify effective ways to intervene and reduce infections. For more information, visit the Beating Buruli in Victoria website.
New antibiotics from old bacteria
Development of new antibiotics is key to addressing the crisis in human health caused by the rise of multi-drug resistant superbugs. Empirical screening of bacteria and fungi for bioactive molecules has been the source of the most successful existing antibiotics. The most prolific producers of these metabolites are the Actinobacteria, but high re‑discovery rates amongst soil-derived organisms demand the testing of new reservoirs of biodiversity and bioactive molecules. Recent studies have shown that human-associated bacteria represent a previously untapped source of antimicrobial diversity. Tim’s group have begun exploring the antimicrobial activity of a diverse culture collection of 700 human pathogenic Actinobacteria held by the state microbiology reference laboratory.
Public health and clinical microbial genomics
Together with Professor Ben Howden, Tim has created the Doherty Applied Microbial Genomics centre – a research centre focused on establishing microbial genomics as a tool for clinical and public health microbiology in Australia. The sequencing capacity and bioinformatics expertise across the Ben and Tim’s research groups makes them uniquely placed to perform and facilitate applied microbial genomics research.
Professor Tim Stinear is a molecular microbiologist and research-teaching academic, leading a team of scientists focused on understanding how certain types of bacteria spread and cause disease. In addition, he is the Scientific Director of the Doherty Applied Microbial Genomics centre and a National Health and Medical Research Council Senior Fellow.