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Regulatory Networks Controlling The Interaction Of Neisseria Gonorrhoeae With The Human Host
Funder
National Health and Medical Research Council
Funding Amount
$361,091.00
Summary
What does Neisseria gonorrhoeae switch on when entering a human cell? Neisseria gonorrhoeae is the causative agent of the sexually transmitted disease (STD) gonorrhoea and globally causes approximately 20-60 million new cases per annum (WHO). Gonococcal infection is the leading cause of pelvic inflammatory disease in women and ~ one third of patients will become infertile. Increased levels of resistance to traditional antibiotics have raised concerns for future treatment options. To date no succ ....What does Neisseria gonorrhoeae switch on when entering a human cell? Neisseria gonorrhoeae is the causative agent of the sexually transmitted disease (STD) gonorrhoea and globally causes approximately 20-60 million new cases per annum (WHO). Gonococcal infection is the leading cause of pelvic inflammatory disease in women and ~ one third of patients will become infertile. Increased levels of resistance to traditional antibiotics have raised concerns for future treatment options. To date no successful vaccine strategies have been developed for this organism, primarily because the cell surface proteins elicit limited immunological protection against other strains. To enable the development of innovative approaches to the control of gonococcal infections, we propose to investigate the regulatory networks in gonococci that are important for initial colonization and survival in the human host. We will examine the role of a class of proteins, called sigma factors, that control the expression of a large number of genes in a concerted fashion. The sigma factors themselves do not recognize environmental signals, but their activity is controlled by a complicated array of proteins that are responsive to changing conditions in the bacterial cell. We have for the first time in any bacterial pathogen, identified all of the genes controlled by sigma factors in the obligate human pathogen, Neisseria gonorrhoeae. We have also found that the mechanisms controlling the activity of the sigma factors in this organism are different to those found in other bacterial pathogens. Our aim is to understand the mechanisms that control sigma factors and to gain insight into how N. gonorrhoeae sense and responds to the host cell during infections.Read moreRead less
Octapeptin-based Antibiotics Against Multi-drug Resistant Gram-negative Bacteria
Funder
National Health and Medical Research Council
Funding Amount
$767,504.00
Summary
Infectious disease is a leading cause of death, and the emergence of "superbugs" in the community and hospitals is of grave concern. We have resurrected a ‘forgotten’ antibiotic from the 1970s that kills superbugs causing pneumonia, skin and urinary track infections; diseases that cause death and discomfort for thousands of Australians today. We will determine how the original antibiotic works against superbugs, and use this information to design better drugs for the future.
New Antibiotics And Treatment Methods Against Drug-resistant Bacteria
Funder
National Health and Medical Research Council
Funding Amount
$766,468.00
Summary
Infectious disease is a leading cause of death, and the emergence of "superbugs" in the community and hospitals is of grave concern. We are developing new, powerful antibiotics that can kill superbugs using ‘forgotten’ drugs from the 1970s. These will combat bacteria that cause pneumonia, skin and urinary track infections; diseases that cause death and discomfort for thousands of Australians today. We will also develop methods to directly remove bacteria from blood infections.
Vancomycin Derivatives Active Against Resistant Bacterial Nosocomial Infections
Funder
National Health and Medical Research Council
Funding Amount
$760,763.00
Summary
Bacterial infection is a leading cause of death worldwide and the emergence of superbugs that are resistant to multiple treatments is becoming a major global concern. Vancomycin is the drug of last resort for the treatment of hospital-acquired Gram -positive bacterial infections. We will synthetically modify vancomycin by incorporating naturally occurring membrane-associative peptides to produce novel antibiotics with multiple modes of action to avoid existing bacterial resistance mechanisms.
Development Of Novel Hybrid Antibiotics For The Treatment Of Hospital And Community Acquired Drug Resistant Gram-Negative And Gram-Postitive Bacterial Infections
Funder
National Health and Medical Research Council
Funding Amount
$715,076.00
Summary
Drug resistant bacteria now pose a serious and growing threat to human health. Many bacteria have developed new resistance mechanisms such that most common antibiotics no longer can protect patients from serious, life-threatening infection. We will modify two existing antibiotics, colistin and carbapenem (a penicillin), to convert it into a more powerful antibiotic that targets resistant bacteria.
This Fellowship will enable research into the basis for life-threatening infection in the critically ill, including severe pneumonia, septic shock and the complexities of antibiotic resistance in bacteria, as well as the translation of this research into practice (including rapid diagnostics).