Dissecting The Molecular Basis For Emerging Alcohol Tolerance In VRE
Funder
National Health and Medical Research Council
Funding Amount
$836,620.00
Summary
Infections caused by vancomycin resistant Enterococcus faecium (VREfm) are a major and growing problem in health care facilities around Australia. We have observed that VREfm is becoming significantly more resistant to killing by alcohol, probably due the increasing use of alcohol-based hand wash products. This project will identify how VREfm is becoming alcohol tolerant, knowledge that will be used to develop alternative disinfection methods or other intervention strategies to stop its spread.
Anti-sporulation Strategies For Clostridium Difficile Infections
Funder
National Health and Medical Research Council
Funding Amount
$651,559.00
Summary
Hospital-acquired infections with the bacterium Clostridium difficile are a major global public health concern with highly virulent isolates emerging overseas in 2002 and in Australia in 2010. These strains have spread through our hospitals and are also found in the community. This project will increase our understanding of how these strains spread and will provide knowledge that is critical for developing improved strategies for preventing these infections.
Defining Burden And Drivers Of Antibiotic Resistant Bacteria And Healthcare Infections To Plan Cost-effective Interventions
Funder
National Health and Medical Research Council
Funding Amount
$340,891.00
Summary
I am an Infectious Diseases physician and early career researcher with interests in drug resistant infections and hospital infections. The research program will describe the threat of drug-resistant infections by demonstrating which superbugs have the greatest impact and by describing how these bacteria disperse through our health system. The research will evaluate and prioritise strategies to confront these problems.
Long-term Macrolide Therapy; Oropharyngeal Dysbiosis And The Spread Of Resistant Pathogens
Funder
National Health and Medical Research Council
Funding Amount
$384,153.00
Summary
Use of macrolide therapy for chronic lung diseases is increasing rapidly. We will determine the impact of long-term macrolide antibiotic use on upper airway bacteria in patients with lung disease, and assess its contribution to antibiotic resistance in the wider community. We will investigate the mechanism by which this therapy achieves benefit and assess interference with bacterial signalling as a means to improve treatment efficacy and reduce induction of antibiotic resistance.
Vitamin D And Acute Lower Respiratory Tract Infection (ALRI) In Indigenous Children
Funder
National Health and Medical Research Council
Funding Amount
$92,669.00
Summary
Australian Indigenous children experience extreme rates of acute lower respiratory infection (ALRI) that medical interventions have failed to reduce. Vitamin D is an important immunoregulatory molecule of the respiratory system that remains uncharacterised in this population. We propose that deficiency contributes to the persistent rates of ALRI. This study will characterise vitamin D levels in a cohort of Indigenous children with and without ALRI. The results will guide future intervention.
Novel Epigenetic Regulatory Mechanisms In Moraxella Catarrhalis And Non-typeable Haemophilus Influenzae: Impact On Vaccine Development And Role In Pathobiology
Funder
National Health and Medical Research Council
Funding Amount
$626,979.00
Summary
Moraxella catarrhalis (Mcat) and non-typeable Haemophilus influenzae (NTHI) are two major causes of middle ear infections in children, and respiratory disease in adults. This project aims to characterise novel regulatory mechanisms associated with disease isolates of these bacteria. This research will aid vaccine development by defining the repertoire of stably expressed potential vaccine targets of Mcat and NTHi, and will improve our understanding of host-pathogen interactions.
Modelling Streptococcal Urogenital Tract Infection To Study Mechanisms Of Bacterial Colonization And Persistence
Funder
National Health and Medical Research Council
Funding Amount
$412,085.00
Summary
Colonization of the urogenital tract with bacterial pathogens is one of the most common infections in humans. In Australia millions of people are colonized in their urogenital tracts at any given time, often asymptomatically, and many such individuals require medical intervention for the treatment of consequent infections that result from persistent colonization. Bacterial colonization of the urogenital tract is associated with a variety of disease presentations including urinary tract infection ....Colonization of the urogenital tract with bacterial pathogens is one of the most common infections in humans. In Australia millions of people are colonized in their urogenital tracts at any given time, often asymptomatically, and many such individuals require medical intervention for the treatment of consequent infections that result from persistent colonization. Bacterial colonization of the urogenital tract is associated with a variety of disease presentations including urinary tract infections and neonatal infections resulting from vertical transmission of colonizing bacteria from mothers to newborns. Aside from sexually-transmitted diseases the most prominent bacterial pathogens that colonize the urogenital tract are Group B Streptococcus (GBS) and Escherichia coli. GBS in particular exist in the female urogenital tract as a persistent microbial reservoir in up to 40% of pregnant women and are transmitted to newborns in up to 72% of live births. Colonization of newborns leads to invasive disease including pneumonia, sepsis, and meningitis. While the disease presentations resulting from colonization of the urogenital tract vary the underlying basis that leads to disease is antecedent bacterial persistence in the urogenital tract despite immune system activation. The mechanisms whereby GBS evade immune responses in the urogenital tract to allow their survival are unknown. I will define the immune-evasion mechanisms and virulence traits used by GBS, as a model urogenital pathogen, to successfully colonize the urogenital tract in the face of mounting immune responses. These studies will provide a better understanding of the pathogenesis of urogenital disease in terms of bacterial colonization and immune-evasion strategies. This will shed light onto new approaches for the prevention and treatment of urogenital disease in humans such as improved vaccination, locally acting cytokines, and deliberate colonization with non-invasive strains for the prevention of disease.Read moreRead less
Iron, Pseudomonas Aeruginosa And Lung Disease In Cystic Fibrosis.
Funder
National Health and Medical Research Council
Funding Amount
$322,875.00
Summary
Cystic fibrosis (CF) is the most common lethal geneticdisease in Caucasians. The worldwide incidence of the disorder is approximately 1 in 2,500 live births. The most significant clinical manifestation of CF is chronic lung infection, particularly with the bacterium, Pseudomonas aeruginosa. Even with the current aggressive antibiotic treatment regimens most patients ultimately succumb to infection with this organism and die before they reach 40 years-of-age. The overall aim of our work is to inc ....Cystic fibrosis (CF) is the most common lethal geneticdisease in Caucasians. The worldwide incidence of the disorder is approximately 1 in 2,500 live births. The most significant clinical manifestation of CF is chronic lung infection, particularly with the bacterium, Pseudomonas aeruginosa. Even with the current aggressive antibiotic treatment regimens most patients ultimately succumb to infection with this organism and die before they reach 40 years-of-age. The overall aim of our work is to increase the understanding of how P. aeruginosa persists in the CF lung, with the goal of developing more effective therapeutic strategies to eliminate chronic infection with this bacterium. The new perception is that P. aeruginosa bacteria flourish in mucus with a low oxygen content within the CF lung and persist despite aggressive antibiotic therapy because they have adopted an antibiotic-resistant, biofilm mode of growth. This has opened up exciting directions for new therapeutic strategies. Factors in CF mucus that regulate this mode of bacterial growth are potential targets for intervention. Our past work has shown that iron is likely to be one such factor. In this study, we will extend these findings and determine whether using iron-binding chemicals can disrupt these biofims and allow the host immune system and antibiotics to work more efficiently to kill the bacteria. Not only will this study provide further insights into the pathogenesis of P. aeruginosa in CF and the role of iron, but ultimately it will contribute to the improved treatment and prevention of chronic infection with this organism.Read moreRead less
Protein Glycan Interactions In Infectious Diseases.
Funder
National Health and Medical Research Council
Funding Amount
$9,182,220.00
Summary
Infectious diseases remain a serious threat to human health, accounting for over 10 million deaths each year. This is a broad-based collaborative proposal, building on our previous achievements. Its aim is to better understand the dynamic interactions between major disease-causing microbes and their human hosts, and to directly apply this new knowledge to the development of improved vaccines and novel treatment strategies. These are urgently needed to combat infectious diseases in the 21st centu ....Infectious diseases remain a serious threat to human health, accounting for over 10 million deaths each year. This is a broad-based collaborative proposal, building on our previous achievements. Its aim is to better understand the dynamic interactions between major disease-causing microbes and their human hosts, and to directly apply this new knowledge to the development of improved vaccines and novel treatment strategies. These are urgently needed to combat infectious diseases in the 21st century.Read moreRead less
Critical Infection: Ecological Solutions To Antibiotic Resistance
Funder
National Health and Medical Research Council
Funding Amount
$561,362.00
Summary
The applicant will apply new types of microbial data and diagnostic tools to early interventions in the critically ill and directly test their impact on clinical outcomes. He will also introduce novel therapies to restore antibiotic susceptibility to enteric bacteria and examine the clinical and microbiological effects of antibiotic decontamination of the critically ill in newly funded project grants. Overlapping research themes all link directly to his clinical and professional roles.