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Dr Tim Barnett

Head of the Strep A Pathogenesis & Diagnostics team, Deputy Director of the Wesfarmers Centre of Vaccines and Infectious Diseases

Tim Barnett

Head of the Strep A Pathogenesis & Diagnostics team, Deputy Head of the Wesfarmers Centre of Vaccines and Infectious Diseases

PhD

timothy.barnett@thekids.org.au

+61 63191319

Tim Barnett is a NHMRC Hot North Fellow at The Kids Research Institute Australia, 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 The Kids Research Institute Australia to investigate disease-causing mechanisms, antibiotic resistance and adverse immunological outcomes associated with GAS skin and throat infections.

Projects

A tonsil organ model to evaluate carriage, disease mechanisms and therapeutic interventions for the treatment and prevention of Group A Streptococcus infections

What risk does underlying trimethoprim resistance pose for the development of cotrimoxazole-resistant skin infections

Tonsil organ model to evaluate carriage, disease mechanisms and therapeutic interventions for treatment and prevention of GAS infections

Improved diagnosis, treatment and prevention of recurrent tonsillitis

Development of methods to rapidly track pathogen and antibiotic resistance profiles from skin sores in Northern Australia (Hot North)

Defining target penicillin concentrations for subsequent studies of a reformulated long-acting benzathine penicillin prototype

Defining Group A Streptococcus interaction with the tonsil epithelium to inform vaccine development

Towards a diagnostic test for rheumatic fever

A diagnostic test for acute rheumatic fever (pilot study)

Science of the swab: optimising Strep A typing from clinical samples

Optimisation of sampling for a new Skin Microbiome assay

Aboriginal Urban Healthy Skin study

Published research

Transmission potential of Streptococcus pyogenes during a controlled human infection trial of pharyngitis

Controlled human infection (CHI) models can provide insights into transmission of pathogens such as Streptococcus pyogenes (Strep A). As part of the Controlled Human Infection with Penicillin for Streptococcus pyogenes (CHIPS) trial, we explored the potential for transmission among participants deliberately infected with the Strep A emm75 strain.

Trimodal skin health programme for childhood impetigo control in remote Western Australia (SToP): a cluster randomised, stepped-wedge trial

Skin infections affect physical health and, through stigma, social-emotional health. When untreated, they can cause life-threatening conditions. We aimed to assess the effect of a holistic, co-designed, region-wide skin control programme on the prevalence of impetigo.

Recombinational exchange of M-fibril and T-pilus genes generates extensive cell surface diversity in the global group A Streptococcus population

Among genes present in all group A streptococci (GAS), those encoding M-fibril and T-pilus proteins display the highest levels of sequence diversity, giving rise to the two primary serological typing schemes historically used to define strain. A new genotyping scheme for the pilin adhesin and backbone genes is developed and, when combined with emm typing, provides an account of the global GAS strain population.

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.

Describing 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.

Antibiotic 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.

Standardization 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.

Standardization 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.

Standardization 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.

Host-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.

In 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.

Penicillin 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.

Inhibition 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.

Searching 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.

Streptolysins 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.

Prophage 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

Genetic 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

SToP (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

Group 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

The 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

Group 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

Group 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.

Education and Qualifications

2000 – PhD, University of Tasmania

Awards/Honours

2017 – Career Development Fellowship, NHMRC Improving Health Outcomes in the Tropical North: A multidisciplinary Collaboration (Hot North)

2011 – Best Postdoc presentation, BacPath 11 conference

Active Collaborations

Asha Bowen – The Kids Research Institute Australia

Phil Giffard, Deborah Holt, Tegan Harris – Menzies School of Health Research, Darwin

Mark Davies, Steven Tong - The Peter Doherty Institute for Infection and Immunity, Melbourne

Mark Walker, Rob Parton – University of Queensland