Novel Inhalation Formulation Of Bacteriophages Against ‘superbugs’ Causing Respiratory Infections
Funder
National Health and Medical Research Council
Funding Amount
$563,621.00
Summary
Emergence of superbugs has led to life-threatening respiratory infections that are resistant to most antibiotics. There is an urgent need for alternative treatments not relying on antibiotics. Bacteriophages (or ‘bacteria eaters’) are natural predators of bacteria and are unaffected by antibiotic resistance. This multi-disciplinary project will develop novel therapeutics using inhaled bacteriophages against bacterial infections in the lungs.
Eradication Of High-risk Bacterial Clones Using Bacteriophages
Funder
National Health and Medical Research Council
Funding Amount
$685,070.00
Summary
Nature offers remedies to the spread of dangerous antibiotic resistant bacteria in the form of predatory viruses (bacteriophages). In this project, we will define optimal mixtures of these for killing problem bacterial types, the mechanisms by which bacterial resistance develops, the best approach to identifying susceptible bacteria and to using these viruses to eradicate them, and we will test a carefully optimised bacteriophage therapy in humans colonised by the dangerous E. coli ST131 strain.
Identifying The Physiological Conditions That Promote Lateral Gene Transfer And Evolution Of New Streptococcal Pathovars
Funder
National Health and Medical Research Council
Funding Amount
$415,907.00
Summary
In the last few decades, the diseases caused by the three human pathogens, groups A, B and G streptococcus have undergone a transformation. The exchange of DNA between these species is speculated to play a role in this changing disease association. In this proposal we will identify the specific physiological and growth conditions that promote DNA transfer. Such information may help in our understanding of how new pathogenic strains of streptococci arise.
Structural And Functional Analysis Of Glucosyltransferases (Gtr) Involved In O-antigen Modification Of Shigella Flexneri
Funder
National Health and Medical Research Council
Funding Amount
$340,976.00
Summary
Shigellosis caused by Shigella flexneri is a medically significant disease in developing countries. Serotypes of S. flexneri are determined by bacterial cell-surface polysaccharides called O-antigens. Bacterial viruses carry the genes which confer O-antigen modification giving rise to different serotypes. The project will address fundamental processes related to the O-antigen modification by studying structure and function of the enzymes encoded by the O-antigen modification gene cluster.
Molecular Basis Of O-antigen Modification And Genomics Of Serotype-converting Bacteriophages Of Shigella Flexneri
Funder
National Health and Medical Research Council
Funding Amount
$268,264.00
Summary
There are approximately 165 million cases of shigellosis world wide annually, resulting in 1.1 million deaths. The majority of cases occur in developing countries and most deaths occur in children under 5 years of age. Shigellosis is mainly caused by the bacterium Shigella flexneri. There are 13 different serotypes of S. flexneri determined by bacterial cell-surface polysaccharides called O-antigens. Bacterial viruses (bacteriophages) carry the genes which confer O-antigen variation. Infection a ....There are approximately 165 million cases of shigellosis world wide annually, resulting in 1.1 million deaths. The majority of cases occur in developing countries and most deaths occur in children under 5 years of age. Shigellosis is mainly caused by the bacterium Shigella flexneri. There are 13 different serotypes of S. flexneri determined by bacterial cell-surface polysaccharides called O-antigens. Bacterial viruses (bacteriophages) carry the genes which confer O-antigen variation. Infection and subsequent incorporation of the virus into the genetic material of the bacterial cell result in modification of the bacterial O-antigen. This phage-mediated O-antigen modification gives rise to different serotypes. The project will address fundamental processes related to the O-antigen modification. This will be achieved by studying structure and function of the enzymes encoded by the O-antigen modification gene cluster. We have isolated several serotype-converting bacteriophages from S. flexneri and we plan to compare and characterise their genomic information to increase understanding of their origin and relationship with the bacterial host.Read moreRead less
Production And In Vivo Delivery Of Bacteriphage Lytic Enzymes By Lactobacillus Fermentum For Disease Prevention.
Funder
National Health and Medical Research Council
Funding Amount
$272,250.00
Summary
Lactic acid bacteria are commonly found in the oral cavity, digestive and female urogenital tracts of humans and other mammals. They are almost completely harmless with only some streptococci and enterococci being able to cause disease. The harmless lactic acid bacteria are mainly classified as Lactobacillus or Lactococcus, and members of of these groups are used in the manufacture of dairy foods such as yoghurt and cheese. Lactobacilli in particular are marketed in a number of health-promoting ....Lactic acid bacteria are commonly found in the oral cavity, digestive and female urogenital tracts of humans and other mammals. They are almost completely harmless with only some streptococci and enterococci being able to cause disease. The harmless lactic acid bacteria are mainly classified as Lactobacillus or Lactococcus, and members of of these groups are used in the manufacture of dairy foods such as yoghurt and cheese. Lactobacilli in particular are marketed in a number of health-promoting or probiotic foodstuffs which are consumed all over the world. We are interested in developing lactobacilli into therapeutic agents which will prevent or treat infections caused by a range of harmful bacteria including the bacteria which cause strep throat and food poisoning. Lactobacilli will be genetically modified to produce enzymes which specifically kill harmful bacteria. These enzymes are from viruses which infect specific bacteria. Using animal models the modified lactobacilli or lactobacilli produced enzymes will be administered orally and tested for their ability to treat possible infections caused by pathogenic bacteria in the oral cavity and intestine. This new therapeutic production and delivery system offers an alternative infectious disease control method to antibiotics. This agent may also be used to control some of the antibiotic-resistant bacteria that are of significant worldwide concern.Read moreRead less