Head of the Strep A Pathogenesis & Diagnostics team, Deputy Director of the Wesfarmers Centre of Vaccines and Infectious Diseases
PhD
Tim Barnett is a NHMRC Hot North Fellow at the Telethon Kids Institute, Perth, and has worked in the area of Streptococcus pyogenes (Group A Streptococcus, GAS) research since his PhD (2000). He pursued postdoctoral studies in two of the leading GAS research laboratories at Emory University (June Scott) and the University of Queensland (Mark Walker), and made a number of significant contributions to this field. These include the first characterisation of the enzymes (sortases) that covalently attach proteins to the GAS cell wall, demonstration that growth phase changes in gene expression are mediated by changes in mRNA stability, and the description of a novel mechanism that GAS uses to evade the innate immune pathway that protects host cells from intracellular bacteria (autophagy).
In 2017, he joined Telethon Kids Institute to investigate disease-causing mechanisms, antibiotic resistance and adverse immunological outcomes associated with GAS skin and throat infections.
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Projects
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Publications
September 2023
Searching for Strep A in the clinical environment during a human challenge trial: a sub-study protocol
Streptococcus pyogenes (also known as group A Streptococcus , Strep A) is an obligate human pathogen with significant global morbidity and mortality. Transmission is believed to occur primarily between individuals via respiratory droplets, but knowledge about other potential sources of transmission via aerosols or the environment is limited. Such knowledge is required to design optimal interventions to control transmission, particularly in endemic settings.
Published research Infectious Diseases Subsite: Wesfarmers Centre of Vaccines and Infectious Diseases Invasive Streptococcus A Disease Healthy Skin and ARF Prevention Strep A Pathogenesis and Diagnostics Strep A & ARF TherapeuticsJanuary 2024Describing skin health and disease in urban-living Aboriginal children: co-design, development and feasibility testing of the Koolungar Moorditj Healthy Skin pilot project
Indigenous children in colonised nations experience high rates of health disparities linked to historical trauma resulting from displacement and dispossession, as well as ongoing systemic racism. Skin infections and their complications are one such health inequity, with the highest global burden described in remote-living Australian Aboriginal and/or Torres Strait Islander (hereafter respectfully referred to as Aboriginal) children. Yet despite increasing urbanisation, little is known about the skin infection burden for urban-living Aboriginal children.
Aboriginal Health & Wellbeing Subsite: Wesfarmers Centre of Vaccines and Infectious Diseases Subsite: END RHD Healthy Skin and ARF Prevention Strep A Pathogenesis and Diagnostics Strep A & ARF TherapeuticsNovember 2023Antibiotic consumption for sore throat and the potential effect of a vaccine against group A Streptococcus: a systematic review and modelling study
Antibiotic consumption can lead to antimicrobial resistance and microbiome imbalance. We sought to estimate global antibiotic consumption for sore throat, and the potential reduction in consumption due to effective vaccination against group A Streptococcus.
Published research Infectious Diseases Subsite: Wesfarmers Centre of Vaccines and Infectious Diseases Subsite: END RHD Invasive Streptococcus A Disease Strep A Pathogenesis and DiagnosticsSeptember 2022Standardization of Epidemiological Surveillance of Group A Streptococcal Pharyngitis
Pharyngitis, more commonly known as sore throat, is caused by viral and/or bacterial infections. Group A Streptococcus (Strep A) is the most common bacterial cause of pharyngitis. Strep A pharyngitis is an acute, self-limiting disease but if undertreated can lead to suppurative complications, nonsuppurative poststreptococcal immune-mediated diseases, and toxigenic presentations.
Published research Infectious Diseases Infectious Diseases Epidemiology Subsite: Wesfarmers Centre of Vaccines and Infectious Diseases Invasive Streptococcus A Disease Healthy Skin and ARF Prevention Strep A Pathogenesis and Diagnostics Strep A & ARF Therapeutics Strep A Vaccines Implementation, Epidemiology & New HorizonsSeptember 2022Standardization of Epidemiological Surveillance of Invasive Group A Streptococcal Infections
Invasive group A streptococcal (Strep A) infections occur when Streptococcus pyogenes, also known as beta-hemolytic group A Streptococcus, invades a normally sterile site in the body. This article provides guidelines for establishing surveillance for invasive Strep A infections. The primary objective of invasive Strep A surveillance is to monitor trends in rates of infection and determine the demographic and clinical characteristics of patients with laboratory-confirmed invasive Strep A infection, the age- and sex-specific incidence in the population of a defined geographic area, trends in risk factors, and the mortality rates and rates of nonfatal sequelae caused by invasive Strep A infections.
Published research Infectious Diseases Infectious Diseases Epidemiology Subsite: Wesfarmers Centre of Vaccines and Infectious Diseases Invasive Streptococcus A Disease Healthy Skin and ARF Prevention Strep A Pathogenesis and Diagnostics Strep A & ARF Therapeutics Implementation, Epidemiology & New HorizonsSeptember 2022Standardization of Epidemiological Surveillance of Group A Streptococcal Impetigo
Impetigo is a highly contagious bacterial infection of the superficial layer of skin. Impetigo is caused by group A Streptococcus (Strep A) and Staphylococcus aureus, alone or in combination, with the former predominating in many tropical climates. Strep A impetigo occurs mainly in early childhood, and the burden varies worldwide. It is an acute, self-limited disease, but many children experience frequent recurrences that make it a chronic illness in some endemic settings.
Published research Skin Infections Infectious Diseases Epidemiology Subsite: Wesfarmers Centre of Vaccines and Infectious Diseases Subsite: END RHD Invasive Streptococcus A Disease Healthy Skin and ARF Prevention Strep A Pathogenesis and Diagnostics Strep A & ARF TherapeuticsNovember 2022Host-dependent resistance of Group A Streptococcus to sulfamethoxazole mediated by a horizontally-acquired reduced folate transporter
Described antimicrobial resistance mechanisms enable bacteria to avoid the direct effects of antibiotics and can be monitored by in vitro susceptibility testing and genetic methods. Here we describe a mechanism of sulfamethoxazole resistance that requires a host metabolite for activity.
Published research Children's Lung Health Subsite: Wesfarmers Centre of Vaccines and Infectious Diseases Subsite: END RHD Invasive Streptococcus A Disease Healthy Skin and ARF Prevention BREATH Strep A Pathogenesis and DiagnosticsJuly 2022In vitro antibacterial activity of Western Australian honeys, and manuka honey, against bacteria implicated in impetigo
Impetigo is a contagious skin disease caused by Staphylococcus aureus and Streptococcus pyogenes. Without treatment, impetigo may be recurrent, develop into severe disease, or have serious, life-threatening sequelae. Standard treatment consists of topical or systemic antibiotic therapy (depending on severity), however, due to antibiotic resistance some therapies are increasingly ineffective.
Published research Skin Infections Subsite: Wesfarmers Centre of Vaccines and Infectious Diseases Healthy Skin and ARF Prevention Strep A Pathogenesis and DiagnosticsJune 2022Penicillin G concentrations required for prophylaxis against Group A Streptococcus infection evaluated using a hollow fibre model and mathematical modelling
Acute rheumatic fever (ARF), an autoimmune reaction to Group A Streptococcus (Streptococcus pyogenes; Strep A) infection, can cause rheumatic heart disease (RHD). New formulations of long-acting penicillins are being developed for secondary prophylaxis of ARF and RHD.
Published research Rheumatic Heart Disease Invasive Streptococcus A Disease Strep A & ARF Therapeutics Implementation, Epidemiology & New HorizonsJanuary 2022Inhibition of the master regulator of Listeria monocytogenes virulence enables bacterial clearance from spacious replication vacuoles in infected macrophages
A hallmark of Listeria (L.) monocytogenes pathogenesis is bacterial escape from maturing entry vacuoles, which is required for rapid bacterial replication in the host cell cytoplasm and cell-to-cell spread. The bacterial transcriptional activator PrfA controls expression of key virulence factors that enable exploitation of this intracellular niche.
Published research Infectious DiseasesSeptember 2021Searching for a technology-driven acute rheumatic fever test: the START study protocol
The absence of a diagnostic test for acute rheumatic fever (ARF) is a major impediment in managing this serious childhood condition. ARF is an autoimmune condition triggered by infection with group A Streptococcus.
Published research Rheumatic Heart Disease Systems Immunology Group A Streptococcal & Rheumatic Heart Disease Computational Biology Systems VaccinologyAugust 2021Streptolysins are the primary inflammasome activators in macrophages during Streptococcus pyogenes infection
Group A Streptococcus (GAS) is a Gram-positive bacterial pathogen that causes an array of infectious diseases in humans. Accumulating clinical evidence suggests that proinflammatory interleukin (IL)-1beta signaling plays an important role in GAS disease progression.
Published research Rheumatic Heart Disease Infectious Diseases Group A Streptococcal & Rheumatic Heart Disease Invasive Streptococcus A DiseaseOctober 2020Prophage exotoxins enhance colonization fitness in epidemic scarlet fever-causing Streptococcus pyogenes
The re-emergence of scarlet fever poses a new global public health threat. The capacity of North-East Asian serotype M12 (emm12) Streptococcus pyogenes (group A Streptococcus, GAS) to cause scarlet fever has been linked epidemiologically to the presence of novel prophages
Published research Infectious Diseases Allergy & Infectious DiseasesJanuary 2020Genetic Manipulation of Group A Streptococcus-Gene Deletion by Allelic Replacement
An optimized, rapid method for creating markerless isogenic mutations that combines Gibson assembly cloning with a new temperature-sensitive plasmid, pLZts
Published research Infectious Diseases Healthy Skin and ARF PreventionSeptember 2019SToP (See, Treat, Prevent) skin sores and scabies trial: study protocol for a cluster randomised, stepped-wedge trial for skin disease control in remote Western Australia
Skin infection burden in remote Aboriginal communities can be reduced by the See, Treat, Prevent (SToP skin sores and scabies) trial
Published research Skin Infections Group A Streptococcal & Rheumatic Heart Disease Healthy Skin and ARF PreventionFebruary 2019Group A Streptococcus co-ordinates manganese import and iron efflux in response to hydrogen peroxide stress
Here, we demonstrate that group A Streptococcus (GAS) utilises Mn(II) import via MtsABC during conditions of hydrogen peroxide stress
Published research Healthy Skin and ARF PreventionJanuary 2019The fall and rise of Group A Streptococcus diseases
We overview the changing epidemiology of Group A Streptococcus infections and the genetic alterations that accompany the emergence of Group A Streptococcus strains
Published research Group A Streptococcal & Rheumatic Heart Disease Healthy Skin and ARF PreventionMay 2018Group A Streptococcus M1T1 Intracellular Infection of Primary Tonsil Epithelial Cells Dampens Levels of Secreted IL-8 Through the Action of SpyCEP
Our results suggest that intracellular infection with the pathogenic GAS M1T1 clone induces a strong pro-inflammatory response in primary tonsil epithelial cells
Published research Group A Streptococcal & Rheumatic Heart DiseaseFebruary 2018Group A streptococcal pharyngitis: Immune responses involved in bacterial clearance and GAS-associated immunopathologies
Innate and adaptive host immune responses are fundamental for defense against streptococcal pharyngitis and are central to the clinical manifestation of disease.
Published research Group A Streptococcal & Rheumatic Heart Disease -
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