Discover. Prevent. Cure.
Patricia Agudelo Romero
Joshua is a second-year PhD candidate with an aim to investigate the potential of bacteriophage therapies for people who suffer from persistent bacterial infections. Cystic Fibrosis (CF) is a fatal genetic disorder in which individuals suffer from a cycle of persistent bacterial infection, followed by antibiotic treatment which results in antibiotic resistance later in life. His aims are as follows; to isolate and characterise a bacteriophage active against a range of resistant Staphylococcus aureus bacteria from CF airways and to provide data supporting the safety of using bacteriophage as an inhaled therapeutic for people with CF
The coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). With new strains emerging, scientists are concerned that these may increase the spread of infection, be more severe, and cause more deaths. The human airway is lined with cells that form a protective barrier to bacteria and viruses. However, these cells are capable of recognising and interacting with SARS-CoV-2, and thus may increase the chances of contracting infection and causing severe disease. With over 45,000 cases and almost 1,000 deaths across Australia itself, the project reflects the need for better understanding of the virus and how it affects the human airways.
Therefore, my study hypothesises that infection with different SARS-CoV-2 variants will result in distinct innate immune responses by human airway cells depending on their origin. Using a systematic approach and 3D cell models, the study aims to assess how the airway responds to SARS-CoV-2 infection. It will also attempt to identify individuals who may be more vulnerable to the effects of infection by comparing airway cells from children (healthy, preterm birth survivors, and children with cystic fibrosis or asthma) and adults (healthy, asthmatic, and those suffering chronic obstructive pulmonary disease). This study will be at the forefront of understanding this virus and its specific effects on human respiratory airways at the cell and molecular level. It will also inform future studies attempting to find complementary therapeutics besides vaccines to reduce the harmful effects of the virus.
Antibiotic resistant infections are a significant threat to modern healthcare, yet there is a lack of investment in developing new antibiotics. The increase in resistance and lack of new antibiotics has a profound effect on people with CF, where antibiotics are essential to treat the frequent airway infections and maintain a person’s health. Therefore, alternatives treatments to antibiotics are urgently required. Bacteriophages, or viruses that only infect and kill bacteria, are a promising alternative to antibiotics as a treatment. However, bacteria can become resistant to long term and repeated exposure to phages. Resistance can be prevented by combining different phages together in cocktail with complimentary antibiotics, but this needs to be better understood.
In my project, I will be using phages to treat Pseudomonas aeruginosa specifically isolated from people with CF, which is important because these bacteria are vastly different to P. aeruginosa that causes other infections. I will monitor the P. aeruginosa for phage resistance and examine the trade-offs for P. aeruginosa becoming phage resistant. These trade-offs can then be targeted through strategic combination of several different phages together and antibiotics, to prevent resistance occurring. We hypothesise that these phage cocktails will increase the effectiveness of therapy and prevent phage-resistance whilst remaining non-harmful to humans.
Chronic bacterial infections are one of the main contributing factors to permanent lung damage and loss of function in the lungs of people with Cystic fibrosis (CF). Mucus build up on the airway epithelial cells results in an ideal breeding ground for opportunistic bacteria like Pseudomonas aeruginosa to grow. Pseudomonas aeruginosa easily develops resistance to the antibiotics typically used to treat it. Presently, intravenous antibiotics are given over an extended period of time, sometimes at very high concentrations which can have significant side-effects including kidney damage. With little investment into discovery of novel antibiotics by the pharmaceutical industry, there is an urgent need to explore alternative therapeutics.
In my project, I will be revisiting the use of bacteriophages, or “phages” to treat Pseudomonas aeruginosa bacterial lung infections in children with CF. Phages are bacterial viruses that use specific bacteria as a host to grow which in turn, kills it. Phage therapy is not a standardised treatment in Australia and many other western countries due to insufficient evidence about their use and effects in humans. However, phage therapy has been commonly used in Eastern Europe as treatment. We hypothesise that specific phages will show high activity against bacteria that cause chronic lung infection without detrimental effects on the body. Ultimately, my project aims to establish a screening tool for high throughput phage assessment and develop a potential therapeutic pipeline to treat affected children.
Els Van der Wiel
Renée La Grange
Nick de Klerk
Emma de Jong
Peter Van Mourik
Telethon Kids Institute
Perth Children's Hospital
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