Bacterial And Host Drivers Of Fulminant Community-acquired Acinetobacter Baumannii Infection
Funder
National Health and Medical Research Council
Funding Amount
$729,315.00
Summary
This proposal aims to understand how a bacterial pathogen causes severe, life-threatening infections in people from the community in northern Australia. This severe infection particularly impacts people who drink excess alcohol or have diabetes mellitus, and importantly impacts Indigenous Australians the greatest. This work will provide, for the first time, important insights into new prevention and treatment strategies for a serious infection impacting Australians and those in our region.
Tuberculosis is one of the most threatening infectious diseases worldwide due to the low efficiency of the only licensed anti-tuberculosis vaccine, BCG. This project aims to interrogate two previously neglected immune mechanisms and their potential to enhance vaccine-induced immunity by incorporating these mechanisms into new genetically modified BCG strains. We will also investigate alternative BCG vaccination routes to generate long-lived immune cells that can rapidly control the infection.
Enhancing Host Defence Mechanisms In Severe Bacterial Infections
Funder
National Health and Medical Research Council
Funding Amount
$830,447.00
Summary
New options to treat bacterial infections are needed because of the rapid increase in antibiotic resistance. One very attractive strategy is to boost the body’s own defence mechanisms against bacteria. This project defines novel molecular mechanisms that can be manipulated to better control a bacterial infection. Novel drugs targeting these molecular pathways are already being developed, albeit for cancer. This project will help assess if these drugs may be useful to treat infections.
Host-pathogen Interactions In Clostridial Myonecrosis
Funder
National Health and Medical Research Council
Funding Amount
$897,617.00
Summary
This project will show how the bacteria that cause gas gangrene interact with host cells in an infection. We will examine the expression of genes from both the host and the pathogen in a mouse disease model. The aims are to determine the impact of bacterial genes that are differentially regulated in an infected lesion, how gene expression of both the host and pathogen is modulated throughout the course of an infection and the role of host pathways in controlling the infection process.
Host innate defence relies on the activation of several signalling pathways that regulate inflammation and cell death. Several important bacterial pathogens of humans inject virulence “effector” proteins into infected cells that interrupt host cell signalling pathways. We recently discovered a family of new effector proteins that directly degrade host proteins and block cell death. Here we will characterise this and other members of the family to understand their role during infection.
Glycosyltransferase Effectors From Bacterial Enteric Pathogens
Funder
National Health and Medical Research Council
Funding Amount
$772,600.00
Summary
Many disease-causing microbes subvert host cell defences to establish infection in part by transporting virulence proteins, termed “effector” proteins, into host cells via specialized protein secretion systems. We have discovered a new family of bacterial effectors that modify host proteins with a sugar and thereby inactivate them. Here we will characterise the function of these effector proteins during infection with E. coli and Salmonella.
Glycosyltransferase Effectors Of Enteropathogenic E. Coli And Salmonella
Funder
National Health and Medical Research Council
Funding Amount
$320,891.00
Summary
This project aims to characterise the mechanisms of disease caused by bacterial pathogens including Salmonella and enteropathogenic E. coli. These pathogens cause a significant amount of diarrhoeal disease and mortality worldwide particularly in infants and in countries where water sanitation is poor. I aim to investigate the specific mechanisms the bacteria employ to manipulate and avoid our immune response during infection in order to better understand and combat diarrhoeal disease.
Combating The Reemergence Of Tuberculosis With New Vaccine Strategies
Funder
National Health and Medical Research Council
Funding Amount
$431,000.00
Summary
Tuberculosis is a major global public health problem with significant morbidity and mortality. This project aims to generate new, highly efficacious vaccination regimens against tuberculosis, especially pulmonary tuberculosis, which is the most difficult manifestation of the disease to control. The outcomes of this project have the potential to save millions of lives worldwide and to decrease socioeconomic burden of tuberculosis, particularly in the context of HIV co-infection.
RP105 Is A New Innate Immune Receptor For Mycobacterium Tuberculosis
Funder
National Health and Medical Research Council
Funding Amount
$525,583.00
Summary
Tuberculosis (TB) is a major global health threat that causes 1.7 million deaths every year. This study will characterise the interactions between the bacteria that cause TB and a new immune sensor. We found that this sensor is involved in controlling TB and this project will determine how it contributes to the immune defence against the infection. Such knowledge will help improve patient management and develop an effective vaccine and better treatments for this devastating disease.
Antibiotic Resistance And Host Immune Evasion In Staphylococcus Aureus
Funder
National Health and Medical Research Council
Funding Amount
$644,428.00
Summary
Staphylococcus aureus is one of the most common bacteria that infects humans. This project aims to characterise the mechanisms that Staph uses to develop resistance to one of our last-line antibiotics, and will determine the effects of this resistance on the ability of the bacteria to cause human disease. The work will also investigate new treatment strategies to tackle this challenging bacteria.