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Purdue associate professor of biological sciences Zhao-Qing Luo, foreground, and graduate student Yunhao Tan identified a new way in which bacteria modify healthy cells during infection. Shown on the computer screen are cells infected with a mutant strain of the bacteria Legionella pneumophila used in their research. (Purdue University photo/Mark Simons)
Purdue University biologists identified a new way in which bacteria hijack healthy cells during infection, which could provide a target for new antibiotics.
Zhao-Qing Luo, the associate professor of biological sciences who led the study, said the team discovered a new enzyme used by the bacterium Legionella pneumophila – which causes Legionnaires’ disease – to control its host cell in order to take up residence.
“Legionnaires’ disease is a severe form of pneumonia, and this finding could lead to the design of a new therapy that saves lives,” Luo says. “At the same time it also provides great insight into a general mechanism of both bacterial infection and cell signaling events in higher organisms including humans.”
Successful infection by Legionella pneumophila requires the delivery of hundreds of proteins into the host cells that alter various functions to turn the naturally hostile environment into one tailor-made for bacterial replication. These proteins tap into existing communication processes within the cells in which an external signal, such as a hormone, triggers a cascade of slight modifications to proteins that eventually turns on a gene that changes the cell’s behavior, he said.
“Pathogens are successful because they know how information in our cells is relayed and they amplify some signals and block others in order to evade the immune system and keep the cell from defending itself,” Luo says. “Despite our understanding of this, we do not know much about how the proteins delivered by the bacteria accomplish this – how they work. This time we were able to pinpoint an enzyme and see how it disrupted and manipulated a specific signaling pathway in order to create a better environment for itself.”
The signaling pathway involved was only recently identified, and the discovery by Luo and graduate student Yunhao Tan also provides a key insight into its process. A paper detailing their National Institutes of Health-funded work is published online in the current issue of the journal Nature.
The signaling pathway involves a new form of protein modification called AMPylation in order to relay instructions to change cell behavior and has been found to be used by almost all organisms, Luo said.
The bacterial enzyme discovered by the Purdue team, named SidD, reverses or stops the AMPylation process, he said.
“It had not been known before if the AMPylation signaling process was reversible or if it was regulated by specific enzymes,” Luo says. “Now we know that it is, and we have a more complete picture that will allow us to use it as a scientific tool to learn more about complex cellular processes. By being able to turn the signaling on and off, we can control different activities and detect mechanisms we wouldn’t see under normal physiological conditions.”
The bacterium affects the host cell’s functions differently during different phases of the infection process, tapping into signaling pathways to turn on and off certain natural cellular activities. SidD stops the AMPylation process four hours after the start of infection in order to reverse an earlier modification that would be detrimental to the cell if left in place, he said.
“During its process of infection, the bacteria can trigger reactions that can lead to the death of the host cell,” Luo says. “Of course this is not in the best interest of the bacteria because it would no longer be able to replicate and continue infection, so it has evolved mechanisms to neutralize such reactions and keep the host cell alive.”
Luo said further investigation of the structure and function of the SidD enzyme is needed to better understand its role in the infection process and its involvement in other cellular processes.
“The more we can learn about an infectious agent, the better equipped we will be to design a therapy to fight it,” he says. “Before a new antibiotic therapy can be created, we must understand the enzyme enough to find chemicals to inhibit its activity. Further, because the bacteria have coevolved with us for millions of years, they provide some of the best tools for us to understand the intricacy of cellular processes.”
Luo plans to further study SidD and investigate other proteins used by Legionella pneumophila bacteria.
POTENTIALLY lethal Legionella bacteria have been discovered in the water supplies for two care homes in Barnet, prompting calls for an inquiry from a trade union.
Staff and residents in Apthorpe Lodge in Nurserymans Road, New Southgate, and Dell Field Court in Etchingham Park Road, Finchley, were sent letters yesterday explaining the situation.
Both facilities are run by Freemantle Trust who were subcontracted by Catalyst Homes, who Barnet Council are due to pay around £7 million following arbitration after a dispute about their care contract.
The elderly are particularly vulnerable to the bacteria, which can cause legionnaires’ disease, and can be contracted by inhaling water vapour.
Common methods of stopping the bacteria from spreading include keeping hot water above 45 degrees Celsius.
Forty pensioners are cared for at Dell Field Court and 50 in Apthorpe Lodge and both were built in 2003.
However, the problems have led to calls from Barnet Unison secretary John Burgess for an inquiry into how the bacteria were allowed to develop.
He said: “These are relatively new facilities, so how does something like this happen. Legionella is a very serious bacteria, who was performing the proper checks?
“Barnet Council needs to run a full inquiry to find out how this happened.”
A statement from Barnet Council said the bacteria were found during routine tests and the water systems have already been treated to “ensure there is no significant danger to residents or staff”.
Legionella ‘hiding’ in treated water
February 22, 2011
BACTERIA that cause the deadly legionnaire’s disease can persist in drinking water even after it has been chemically treated, according to the results of research in Sydney that suggests a need for increased testing.
The bugs can hide inside amoebae – generally harmless micro-organisms resistant to chlorine disinfection – which may later burst to release pathogens, say University of NSW scientists.
The phenomenon could explain a rise in the disease despite filtration and disinfectants in public water supplies.
A microbiologist at the University of NSW, Jacqueline Thomas, began researching amoebae in drinking water after legionella was found in Nepean Hospital’s water system and a car wash in Victoria in May 2008.
”[We wanted] to find how legionella was growing and spreading through water systems even after extensive treatment with chlorine and other filtration methods,” she said.
In NSW, infections from the bacteria increased between 2004 and 2007 and have since stabilised. The young, elderly and people with compromised immune systems are the most susceptible to the infection.
Ms Thomas said identifying the extent to which drinking water contributed to legionella infections in NSW was difficult because of limited testing and poor tracing of infections to their environmental source. But the Centres for Disease Control and Prevention in the United States found legionella accounted for 29 per cent of all drinking-water-borne disease outbreaks in that country between 2001 to 2006.
State water utilities are not required to regularly test for amoebae or legionella in their treatment and distribution systems under the Australian Drinking Water Guidelines, which are set and reviewed by the National Health and Medical Research Council.
Ms Thomas and her colleague Nicholas Ashbolt found bacteria such as legionella can become more infectious living inside amoebae.
”They can actually grow and replicate quite well in there, and because amoebae are bigger organisms they are resistant to drying out from chlorine to a larger degree,” said Ms Thomas, who is completing her doctorate with the university’s Water Research Centre. ”The thing that was really surprising was just how frequently amoebae were detected across all types of drinking water systems. It was a lot higher than anyone in the water industry had anticipated.”
Sydney Water said it used adequate disinfection and managed its flow rates to avoid stagnant water and increased temperatures to minimise the growth of amoebae and legionella.
Drinking water is tested and monitored at every stage of the supply system, including after it is treated, in distribution pipes and at customers’ taps, a spokesman said.
But Ms Thomas found amoebae could also breed inside house pipes, shower heads and taps.
Ms Thomas’s review of international research is published in the journal Environmental Science & Technology.
The water-borne infections that struck guests of the Playboy Mansion are more common than you think.
According to the Los Angeles County Health Department, about 200 people who attended a recent Playboy Mansion fundraiser were infected by Legionella bacteria. Four of them came down with Legionnaires’ disease, a sometimes deadly pneumonia; the rest had Pontiac fever, a flu-like illness that lasts about three days.
As many as 18,000 people in the United States contract Legionnaires’ disease each year, according to the Centers for Disease Control and Prevention (CDC), 5% to 30% of whom die from it within a few days or weeks.
About 90% of Legionnaires’ cases go undetected, in part because physicians treat the pneumonia but don’t test for Legionella bacteria.
“That’s a big problem,” says Matt Freije, author of Protect Yourself from Legionnaires’ Disease: The waterborne illness that continues to kill and harm. “If Legionella is not recognized as the cause of the infection, then no investigation is performed to pinpoint and fix the plumbing system, hot tub, or other water system that caused it, and that water system can continue to make people sick.”
Pontiac fever is even less likely than Legionnaires’ disease to be diagnosed because it is less severe. Most of us don’t even go to the doctor when we get the flu, let alone try to find out what caused it. Generally, Pontiac fever is recognized only when physicians in the same vicinity report several flu-like illnesses at the same time, attracting the attention of the health department, as with the Playboy event.
According to Freije. “Laws in much of Australia and Europe require building owners to maintain water systems to minimize Legionella bacteria but prevention is not mandated in the United States. I have received emails from many Legionnaires’ survivors who were outraged to find out they suffered from a disease that is preventable.”
Steve Sederstrom is one of the Legionnaires’ survivors who tells his story in Freije’s book. “My experience with Legionnaires’ disease was the worst thing I have ever been through. After five months I still have a major problem with short-term memory-I forget where I am going, or forget people’s names even though I have known them for years. I am afraid that I will never get my memory back.”
Holidaymakers who have visited Bali recently have been urged to see their doctor if they develop flu-like symptoms following an outbreak of Legionnaires’ disease on the Indonesian island.
Four Victorians have contracted the disease while holidaying in Bali in the past six months, including two men who visited in late December.
Victoria’s Chief Health Officer Dr John Carnie said a further six people had fallen ill with the disease in Western Australia after recent trips to Bali, prompting a warning to all those who fell ill after visiting the island.
“The Indonesian Government has been advised of the Australian cases and is investigating to determine the source of the infections,” Dr Carnie said.
Dr Carnie said the four Victorian men, aged from 45 to 82, had been treated for the illness after returning to Victoria and had recovered.
The first two Victorian cases were in August and October, while the latest two had visited Bali in late December.
Legionnaires’ disease causes flu-like symptoms such as headaches, fevers, chills and muscle aches, followed by respiratory problems and pneumonia developed over three or four days.
The symptoms can take up to 10 days to develop after the initial contact with the bacteria.
Groups at high risk of contracting the disease are people aged over 50, heavy smokers, heavy drinkers, diabetics, and people with chronic lung disease.
Dr Carnie said the legionella bacteria occurred naturally in the environment, predominantly in water and soil.
It is normally in very low concentrations but can increase, particularly in man-made aquatic environments with warm recirculating water, such as air conditioning cooling towers.