Energy Enzyme a Unique Target for Treating Malaria
First Published: Enews - February 2011
Flinders University researchers have uncovered a potential new target for treating Malaria by focussing on the parasite's production of energy.
Malaria is an infectious mosquito-borne disease responsible for fever, headache, and vomiting. If not treated, malaria can quickly become life-threatening by disrupting the blood supply to vital organs.
While almost eradicated from most Western countries through effective mosquito control, developing countries still suffer and the disease is responsible for close to one million deaths per year. Many of these deaths are in children in sub-Saharan Africa.
In many parts of the world, Malaria has developed resistance to a number of previously-effective medications and it is feared resistance will develop to the current most effective treatment.
Dr Ian Menz, Head of the School of Biological Sciences at Flinders University and his team have uncovered a difference in the way Malaria and other related eukaryotic protist parasites produce energy.
All living organisms rely on the energy production enzyme adenosine triphosphate synthase (ATP synthase) for providing their cells with energy.
Dr Menz and his team have discovered a number of genes that contribute to the ATP synthase found in all other living organisms are missing in Malaria and similar organisms, and are replaced by new genes.
"If we can identify that ATP synthase is vital to the survival of Malaria, we will then be able to target these genes unique to this group of parasites with a drug which will eliminate them without harming any healthy cells," Dr Menz said.
"Working with a team in Melbourne, the first stage of this research will be to test the importance of ATP synthase in Malaria by genetically engineering the parasite so that known genes that code for the enzyme can be switched on and switched off.
If switching off the genes lead to the death of the Malaria, the team can deduct that the ATP enzyme is vital to the parasite's survival and therefore is a worthy target of a new drug treatment.
Unravelling The Secrets Of A Sneaky Protein
First Published: Investigator - December 2009
Flinders researchers are unravelling the secrets of a tricky protein in their efforts to quash drug resistance in hospital strains of ‘golden staph’.
They hope that by learning more about the physiology of the protein – known as QacA – they can learn how to overcome its drug resistance.
However, the research team concedes the sneaky nature of the protein is making their task a challenge.
‘It’s a very adaptable protein that sits on the outer surface of a cell and can recognise more than 30 chemical compounds – including antiseptics and disinfectants commonly used in hospitals,’ Dr Melissa Brown, Associate Professor in the School of Biological Sciences at Flinders University said.
‘Once it recognises a chemical it sets to work pumping it out of the cell before the chemical reaches its target.’ She said its very inventiveness was probably one of the secrets behinds its success.
Staphylococcus aureus, often referred to as golden staph, is a common bacterium that lives on the skin or in the nose of human beings.
In most situations it is harmless, however if it enters the body through a cut in the skin it can cause infection and even death in extreme cases.
While most infections caused by golden staph are treatable with antibiotics, often a few bacteria will survive a course of antibiotics, perhaps due to gene mutation or obtaining genetic information from other surrounding antibiotic-resistant bacteria.
The resulting antibiotic-resistant Staphylococcus aureus bacteria that remain then flourish, since they no longer have to compete for resources with the rest of the colony.
Hospital patients with surgical or other wounds are particularly susceptible to golden staph and can become seriously ill if their golden staph infection resists treatment from antibiotics.
Dr Brown said the ultimate aim of her team’s National Health and Medical Research Council funded study was to learn enough about drug pumps like QacA so that pharmaceutical scientists could design new drugs to combat it.
‘The more basic science you have about the physiology of a bacteria the more likely you are to learn how to overcome them,’ Dr Brown said.
Seeking Best Swine Flu Defence
First Published: Investigator - July 2009
Up to 100 people with confirmed cases of seasonal flu and swine flu will take part in a new study at Flinders Medical Centre to investigate how the body protects itself against the viruses.
The study will examine the immune response to normal seasonal influenza and the newest strain of influenza A - human swine influenza H1N1 (swine flu).
Head of Microbiology and Infectious Diseases at SA Pathology, Flinders Medical Centre and Flinders University Professor David Gordon said the study will have major benefits for predicting the likely spread of influenza strains in the community.
‘The findings will also be very important in planning vaccination programs against new strains of influenza,’ he said.
Researchers will identify study participants from laboratory results at Flinders Medical Centre. A sample of blood will be taken 2-3 weeks apart - once at the time of infection and two weeks later - to measure influenza antibodies which are formed in response to infections or vaccinations.
‘If people form an antibody response (protective immune response) we will be interested to see how long that antibody lasts, or whether it disappears,’ Professor Gordon said.
A second part of the study will answer questions about cross protection against other forms of influenza.
‘We will be looking at whether antibodies to swine flu are formed after infection, how long they last and if antibodies from people with seasonal influenza can provide cross-protection against swine flu.
‘There is also some suggestion elderly people may have protection against swine flu, so we are interested to know if there is background immunity in this population.’
Professor Gordon and his team at Flinders have developed a unique way to use a test known as an assay to accurately measure antibodies that form in response to swine flu or seasonal flu.
‘In the case of influenza A, antibodies against a surface protein of the virus called haemagglutinin form during infection and result in long term protection against re-infection with that particular influenza A strain,’ he said.
‘We have developed a method where we can get cultured cells to express cloned seasonal or swine haemagglutinins on the outside of their surface, enabling measurement of antibodies against these proteins.
‘If antibodies are detected that bind to these cells it means they are reacting against a particular haemagglutinin which almost certainly means immunity.’
Earlier The Better For Hep C Treatment
First Published: Investigator - June 2009
An international trial involving researchers from Flinders has shown that treating the most common strain of hepatitis C in its early stages may double the chance of a cure.
The trial – involving more than 700 patients from 33 Australian hospitals including Flinders Medical Centre – found that if hepatitis C was treated when there was minimal or no liver damage in the patient, the chances of a cure doubled compared to patients treated in the later stages, when liver damage was more advanced.
‘The findings are important because they confirm that the current standard of care for people living with the most common form of hepatitis C, called genotype 1, is effective,’ Dr Alex Rogers, a consultant gastroenterologist hepatologist based at Flinders Medical Centre said.
More importantly, the findings suggested that cure rates in genotype 1 could be a lot higher than previously thought.
Researchers found that up to seven out of ten people with this form of hepatitis C could be cured if treatment commenced at the early stages of the illness, before any significant liver damage occurred.
Hepatitis C is a virus that causes liver inflammation and liver disease. More than 200,000 Australians have chronic hepatitis C and 10,000 new infections are diagnosed in the nation each year. While there is no vaccination against hepatitis C, treatment in the form of Pegylated Interferon and Ribavirin is available.
The aim of the Australian-led international clinical trial was to compare the effectiveness of the two treatment regimens in reducing or clearing the hepatitis C virus in patients infected with HCV genotype 1.
Dr Rogers said the research was positive news for people living with hepatitis C, and hopefully gave people greater incentive to seek treatment.
‘Only a very small percentage of Australians living with chronic hepatitis C are actually receiving treatment, so we hope these findings encourage a greater number of people to seek help.’
Dr Rogers said the risks of failing to seek treatment could be significant: ‘People risk ongoing liver disease and liver failure.’
What is whooping cough?
First Published: Investigator - December 2008
Whooping cough, or pertussis, is a bacterial infection of the nose, throat and lungs caused by the bacteria Bordetella pertussis. The infection is so named because the long coughing spells, particularly in children, generally end with a ‘whooping’ noise as the child finally takes a massive gasping breath through an obstructed airway. Some children may vomit at the end of the episode. Coughing spells can last for several minutes and the sufferer can experience several bouts each hour. Children may have coughing bouts during sleep and the infection can last for many weeks. Older children and adults can have whooping cough without the classical ‘whooping’ sound. They have coughing spells lasting a minute or more, followed by several minutes of not coughing. The coughing spells seem to be caused by thick mucous in the lungs, which is difficult to cough up. Pertussis kills about 300,000 children worldwide each year. In Australia between 1993 and 2004, 18 children – mostly aged under 12 months old – died as a result of whooping cough. Immunisation against whooping cough can be very effective in protecting against the infection but the vaccine effectiveness falls with time.
Is whooping cough contagious?
Yes, whooping cough is very contagious. Around 70 – 100 percent of people living in the same house as someone with whooping cough will contract the infection (unless they have been immunised in the last 11 years or have had the infection). The infection is spread by ‘droplets’ that are coughed or sneezed out. These droplets can be breathed in or they can be carried to the nose by hands which come in contact with the droplets (eg through handling used tissues or by touching surfaces which have the droplets on them).
Who is most at risk?
Any one who is not protected (by recent immunisation or by having had the infection before) can get whooping cough, including older children and adults. Most people who get the infection in Australia are adults or young people over 11 years of age - even if they have been immunised as a baby. Babies are at most risk of having severe health problems from whooping cough. About 1 in 200 babies who get whooping cough before they are six months old will die from the infection.
Signs and symptoms of whooping cough
Whooping cough usually starts off like the average cold/cough, but develops into long bouts of repeated coughing fits after three to seven days. Children generally have many quick coughs in one spell and often ‘whoop’ at the end. Infants may turn blue, develop bulging eyes and tongue protrusion during episodes. Vomiting and weight loss are common. Very young babies may not cough, but instead, can stop breathing for a minute or longer many times per day. If they cough there might not be the whoop. Adults and older children may not whoop, but they will have persistent coughing spells and they may feel tired and generally unwell.
Diagnosis of whooping cough
Whooping cough may be suspected from symptoms, however laboratory tests are essential to confirm the diagnosis. At Flinders a test to detect the genetic material of B pertussis from a throat swab (PCR test) is performed, and this is the best diagnostic test. Blood tests to measure pertussis antibody are less reliable and are not recommended. X-rays may be taken to look for complicating pneumonia.
Whooping cough is generally treated with antibiotics. This will kill the bacteria but it does not stop the coughing which may go on for many weeks, unless the antibiotic is given very early in the illness. Young babies with whooping cough are often so ill that they need hospital treatment. Cough suppressing medicines may be helpful for adults. Part of the reason for coughing is that there is sticky mucous in the airways which needs to be coughed up. Always check with your doctor before giving a child a cough suppressing medicine. Children and adults exposed to whooping cough should seek advice from their doctor as they may require antibiotics to prevent infection occurring and further transmission of the disease.
What you can do
- Ensure your child is well hydrated and that they are eating enough
- Try feeding a young child immediately after a coughing spell. (Feeding often triggers a coughing spell if the child has not coughed recently, but soon after a coughing spell food and drink are generally well tolerated)
- Children who are coughing often will be tired and uncomfortable (coughing can cause tummy pain from overused muscles). Paracetamol may help with aching muscles.
Controlling the spread of whooping cough
Infants should be vaccinated against whooping cough at two, four and six months, followed by a booster dose at four years. A further single booster dose is now recommended in South Australia for the following groups:
- 13-14 year olds
- Parents planning pregnancy
- Parents of a newborn baby, as soon as possible after delivery
- Adults working with young children, especially child care and health care workers
- Adults aged 50 who have been vaccinated in the past.
This Health Talk article was compiled with the assistance of Professor David Gordon from Flinders Medical Centre; You’ve Got What? SA Department of Health; and Child and Youth Health (South Australia).
World First Trial Of ‘Sweet’ Flu Vaccine
First Published: Investigator - July 2008
A trial of a plant extract enhanced influenza vaccine – one of the largest single-centre trials of its type in the world – is being conducted at Flinders Medical Centre.
Researchers are seeking up to 1,000 participants to trial the standard flu vaccine ‘boosted’ with a natural plant sugar.
The team has already demonstrated that the enhanced vaccine is effective in improving immunity against influenza in healthy people, and now hopes to show it improves immunity in the aged and chronically ill who are most at risk of complications when they get the flu.
‘Although the vaccine is still in its trial stage, we are hoping that this will prove to be the best defence against an influenza epidemic,’ chief investigator Dr Dimitar Sajkov said.
Vaccines are made up of two components: an antigen, which is a modified form of the influenza virus that enables the body to recognise and respond to the real thing; and an adjuvant, which acts as a ‘booster’ and amplifies the immune system’s response to the virus to make the vaccine more effective.
Scientists around the world have been searching for a suitable adjuvant to boost the effectiveness of the flu vaccine for decades without success.
A Flinders team led by Director of Diabetes and Endocrinology, Professor Nikolai Petrovsky has discovered that a natural sugar based adjuvant safely boosts the effectiveness of current commercial flu vaccines.
‘In a safety trial of 220 volunteers last year we were able to demonstrate that the adjuvantboosted flu vaccine was not only safe, but also very effective in terms of producing more immunity against the flu virus,’ Professor Petrovsky said.
He said adding the sugar-based adjuvant made the flu vaccine many times more effective. ‘Basically, you get to use less vaccine but get more immunity when you add the adjuvant.’
‘So in the event of a pandemic we could potentially stretch precious vaccine supplies up to 10-fold, enabling us to protect 10 times more people than with the traditional vaccine.’
Four groups are being targeted for the trial: people with chronic lung disease, heart disease, kidney disease, diabetes or healthy people aged over 60 years. Participants should not have already received a flu vaccination this year.
Those selected for the trial will receive either the standard flu vaccine or the adjuvant enhanced flu vaccine and then be followed up for a 12-month period. Researchers will determine from regular blood tests which vaccine provides participants with better protection against the flu.
Unlocking The Key To Virus Entry
First Published: Investigator - July 2008
Researchers at Flinders Medical Centre are trying to unlock the key to how one of the world’s most common respiratory viruses hitches a ride into human cells.
Human metapneumovirus (hMPV) is a major cause of respiratory tract infection in children, and also causes severe infection in the elderly and people with a compromised immune system.
Researchers hope that by working out how the virus attaches to human cells they can one day work on a method to block this first step in viral infection.
‘We’re looking at the mechanism hMPV uses to attach to cells. Once we discover that it will open the opportunity to block the action,’ said Professor David Gordon, the head of Microbiology and Infectious Diseases at Flinders Medical Centre.
The team also includes PhD student Anne Thammawat and Senior Scientist Dr Tania Sadlon and is particularly focusing its investigation on cellular glycosaminoglycans (GAGs).
‘GAGs are sugar structures present on all cells, and there is strong evidence that human metapneumonvirus use GAGs for cellular entry,’ said David.
The team is also studying the role played by the hMPV G protein, which is present on the surface of the virus and is thought to mediate attachment to cells.
‘We’ve been able to clone the G protein and are now testing its interaction with GAGs,’ David said. ‘The next step is to better understand the structure of G protein.’
‘This is important because the information will allow us to potentially design inhibitors to block infection.’
David said the research was important because respiratory tract infections are the most common infections in humans, and continue to be the leading cause of acute illness and mortality worldwide.
‘The impact on health in Australia is likely to be comparable to the United States, where respiratory tract infections are the sixth leading cause of death and account for more than half a million hospital admissions and 8-10 million outpatient visits each year,’ he said.
Antibodies For Avian Influenza
First Published: Investigator - April 2006
Professor David Gordon, Dr Tania Sadlon and Dr Peter Hallsworth from Microbiology and Infectious Diseases are working on developing a new diagnostic test for Avian Influenza (Bird Flu).
The aim of this project is to develop a blood test to discover whether human antibodies can be formed when there is exposure to avian influenza.
The body’s immune system uses antibodies to identify and neutralise the effects of bacteria and viruses. They are very specific to a particular virus and can only develop when a person has been exposed to that disease. Importantly, they are required to develop immunity.
However, because the avian flu is not related to normal strains of influenza, humans have no pre-existing immunity to these viruses.
Using gene technology, the research team will clone the H5 surface protein of the avian flu virus, which by itself is harmless.
The H5 gene will then be introduced into a yeast cell which will continue to produce this small component of the virus for the researchers to use in developing the blood test. By extracting the H5 protein and adding a sample of blood they will be able to see if antibodies are formed and bind to it.
This will give an indication of the body’s natural ability to develop antibodies against the avian flu virus. From this testing it will be possible to determine how the disease may spread, how many people will develop immunity and, the potential number of people who may become infected.
Another potential benefit from this test is the ability to measure antibodies and see if a vaccine will be effective. This would involve administering the vaccine, then running the developed blood test to see if antibodies exist.
“If an outbreak were to occur then an understanding of the pattern of infection, the potential mortality rate and the level of infection is vitally important in preparing strategies to deal with this,” says Professor Gordon.
How Bacteria Defeats The Immune System
First Published: Investigator - October 2005
Professor David Gordon, Head of the Department of Microbiology and Infectious Diseases, and his team of researchers at Flinders are endeavouring to understand how a particular strain of bacteria is able to escape the body’s immune system.
The streptococci bacteria is commonly found in the throat or skin and while harmless to some, others can experience a range of mild symptoms such as tonsillitis to the severe symptoms associated with the Group A strain.
Group A Streptococcus is potentially an extremely aggressive organism whose effects can lead to overwhelming infection such as disease of vital organs, rheumatic fever and destruction of the skin and soft tissues, better known as “flesh eating disease”.
Diseases of the kidneys and heart associated with this bacterium can develop due to tissue damage directly caused by reactions of the immune system. For example, proteins within this strain of bacteria are very similar to those found within the heart valves. When the body is under threat by Group A Streptococcus the immune system attempts to kill this bacteria, unfortunately also attacking the healthy proteins within the heart.
Dr Gordon and his team are working at a molecular level, focusing on how the Group A Streptococcus works its escape from the body’s immune system.
So far Dr Gordon and his team have found that part of this harmful bacterium binds a specific part of the body’s immune defences, the complement system, rendering it unable to kill this bacteria as it normally would. The team has also identified a receptor on human cells that allows this bacterium to attach to the skin and throat.
“The reason it is so important we understand how bacteria escapes the immune system is so better targets for vaccines can be identified and alternative preventions and treatments devised,” says Dr Gordon. “It is also relevant to our knowledge of how the immune system operates and for understanding how other or new strains of bacteria might cause disease.”