Legionella was very nearly the species I was going to work on for my honours and PhD but alas I chose a different lab and begun my work on Streptococcus instead. Since then I have made an effort to follow Legionella research as this adaptable little dude can cause pretty significant issues, and it doesn’t even like living in humans!
Why ‘Legionnaire’s Disease?
‘Legionnaire’s Disease’ was coined after a series of cases presenting in Philadelphia during 1976. It seemed to only being affecting middle aged to elderly men and those that presented to hospital were getting very sick very quickly. It turned out all the men presenting to hospital had recently attended an American Legion (what the hell is that?) meeting at the Bellevue Stratford Hotel. These men had survived war and many were heavy smokers and/or drinkers. Physiologically speaking, these men were prime candidates for respiratory infections. It just so happened that the air-conditioning cooling towers were chock-a-block with Legionella pneumophilia which was being pumped into the rooms in high concentrations.
Legionnaire’s Disease like seemingly everything else presents initially with generalised flu like symptoms but can be differentiated on X-rays once it has reached the stage of pneumonia. Most bacterial and viral pneumonias are localised to one or a small number of locations in the lung but Legionella is moved very quickly around the lungs by macrophages allowing it to spread throughout the lungs. This gives the X-rays a ‘foggy’ or ‘moth-eaten’ appearance. Because the bacteria is everywhere in the lungs pneumonia is a pretty big deal and many people who progress to pneumonia are significantly impaired for the rest of their lives due to the large amount of lung damage.
Two features set Legionella apart from other similar bacteria. Unlike most bacteria Legionella utilise amino acids for food, instead of carbohydrates and it does not spread from person to person. That means each case of Legionnaire’s Disease is isolated and new. Both of these differences point to an alternate path to human disease than most pathogens take.
Legionella – The Accidental Pathogen
It is now widely accepted that the cause of disease in Legionnaire’s Disease is mediated primarily but hijacking of macrophages by the bacteria. Once inside the macrophage the bacteria replicate rapidly and eventually lyse the macrophage. By targeting and killing the defensive cells first the infection can develop rapidly and as macrophages contain many chemicals involved in eliciting an immune response the infection can get very bad very quickly. The debris from the macrophages can kill off other cells in the lungs resulting in fluid leakage and eventually pneumonia. The other implication in killing of the macrophages first is that following an infection it is the macrophages that initiate rebuilding. Without them rebuilding is stalled and some patients never recover.
The unusual characteristics I mentioned above, considered alongside the ‘macrophage first’ policy of the disease has led to an interesting discovery. Legionella are only pathogens by accident, they normally live in amoeba! This was a pretty amazing find as macrophages are to bacteria in your body as amoeba are to bacteria in the environment, with a few subtle differences. They both even look the same!
Unfortunately both are difficult. Let’s look at treatment first.
Most bacteria that respond to antibiotics live in the ‘external environment’ that is outside the cells. This is advantageous as the drug also has to get from the site of entry to the site of infection before it can have activity, if the bacteria is just there then it can work straight away. If, like Legionella, the bacteria are inside another cells like a dangerous nesting doll set it makes it very difficult for the drugs to work. Irrespective of whether the drugs work or not lung rebuilding often takes a long time so even effective drug administration may not save a severely infected patient.
The most effective option for control is prevention. This is difficult as in the environment the bacteria are often hidden inside amoeba allowing them to withstand most cleaning agents. An effective but extraordinarily expensive option to treat water and remove both Legionella and the host amoeba is to pass the water through hot pipes (60°C or higher) whilst also exposing the water to UV light. It seems our best option is to try and control the amoeba first to in turn eliminate the bacteria but we are some way off from even being able to do that effectively.