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Working with tropical infectious diseases may not be everyone’s dream job, but for South Australian researcher, Jessica Webb, she is dedicated to pursuing her interest in this field.

From a young age, Webb’s father was very unwell due to stress at work, and eventually ended up in hospital where he acquired the bacteria known as Methicillin-resistant Staphylococcus aureus (MRSA). To this day he continues to take antibiotics on a daily basis, and failure to do so may mean that the bacteria will cause serious infections, building its resistance to antibiotics.

Webb’s father being in and out of hospital for most of her childhood left an impression on Webb and ignited her to enrol in a science degree at Flinders University majoring in micro and molecular biology, with the plan to research life threatening pathogens. This would allow her to better understand the genetics behind the ability of pathogens to infect their host and cause disease.

After working on the virus Human parechovirus (HPeVs) during her placement at Flinders Hospital, she realised that she wanted to have a career with a clinical focus. Webb then made the move to Darwin to begin her work on tropical infectious diseases.

Webb’s focus is on Burkholderia pseudomallei the causative agent of the fatal disease Melioidosis, which is endemic in Darwin. The estimated global mortality rate of melioidosis sits at around 90,000 deaths per year, and is comparable to that of measles.

Melioidosis remains as a great threat to the health of many Territorians. Cases of Melioidosis in the Northern Territory, particularly the Top End have some of the highest rates of incidences documented globally. Also known as the ‘Darwin Disease’, Burkholderia pseudomallei (Bp) is the causal bacterium for melioidosis, and is largely underdiagnosed, living in soils and muddy waters, coming to the surface often after drenching rains.

“Even with antibiotic therapy, mortality remains stubbornly high, ranging from ~10% in Australia to ~40% in Thailand, with the majority of cases being associated with the wet season,” said Webb. “Bp is also an extremely pathogenic organism and is equipped with machinery encoded in its DNA to cause different disease severities.”

Humans can contract the bacteria through cuts and sores in the skin, or by inhaling contaminated water, dusts or droplets. Bp is inherently resistant to multiple antibiotics, meaning that effective treatment of these multi-resistant organisms is of great importance due to the already limited treatment options. In northern Australia and Southeast Asia, where melioidosis is endemic, infections caused by Bp are a major cause of bacterial pneumonia and blood poisoning. Depending on where the infection develops, common and early symptoms can include fever, a cough and breathing difficulties.

Generally, risk factors for melioidosis include; diabetes, alcohol related problems and renal disease. However there is a higher number of melioidosis cases reported in Indigenous Australians due to the increased chance of being exposed to the bacteria and due to the risk factors including diabetes renal disease being more prevalent in the Indigenous population.

“Even with antibiotic therapy, mortality remains stubbornly high, ranging from ~10% in Australia to ~40% in Thailand, with the majority of cases being associated with the wet season,” said Webb. “Bp is also an extremely pathogenic organism and is equipped with machinery encoded in its DNA to cause different disease severities.”

Treatment remains difficult. Due to concerns about rapid disease progression and difficulties with complete eradication due to bacterial latency, melioidosis treatment relies on prolonged administration of antibiotics that can last up to six months in duration.

Jessica Webb

Webb’s PhD project studies the mechanisms by which Bp becomes highly resistant to antibiotic treatment. Using whole genome sequencing technology, Webb can look at isolates from melioidosis patients where antibiotic resistance has developed.

“Armed with this knowledge, my project provides the potential for medical professionals to use a new class of drugs known as efflux inhibitors to alter the phenotype of the bacteria so that they are no longer resistant to these drugs.”

Her hypothesis is that antibiotic resistance in these patients is mediated by specific genetic changes in Bp that affect efflux, a process in which compounds including antibiotics can be exported out of the cell. She has found mutations in a certain gene that consequently lead to higher levels of antibiotic resistance. Webb has also found a never before identified mutational mechanism in Bp which also renders the bacteria resistant – the antibiotic does not ‘bind’ to the cellular target.

“My results show that Bp can mutate in previously unknown ways to evade antibiotic pressure within the course of an infection, leading to treatment failure and, often, death,” she said.

“Armed with this knowledge, my project provides the potential for medical professionals to use a new class of drugs known as efflux inhibitors to alter the phenotype of the bacteria so that they are no longer resistant to these drugs,” explained Webb.

Her work can help doctors to more rapidly identify resistant isolates from infected patients and to personalise more effective treatment for each individual patient.

“The findings from my project will give patients the best chance of survival from this devastating infectious disease,” she said. “If we identify the presence of these genes in a rapid manner, patients can be treated more aggressively to eradicate these pathogenic strains before they develop into severe infections.”

Congratulations are extended to Jessica Webb for her 2016 Australian Federation of Graduate Women (AFGW) Barbara Hale Fellowship award, made possible by a bequest from the estate of Barbara Mary Hale (1924-2013), a university librarian, the first female elected to the University of Western Australian Senate and Past President of University AFGW Barbara Hale Fellowship

For more information on melioidosis, visit:

https://nt.gov.au/wellbeing/health-conditions-treatments/bacterial/melioidosis
http://www.who.int/en/
https://www.cdc.gov/

featured image: University of Liverpool Faculty of Health & Life Sciences, microscope up close/ FlickrCC