In the 21st Century we have already identified a number of infectious organisms that can and will present a major problemIn the last three decades we have seen several viral and bacterial epidemics take place at a time when we would have expected the eradication of many infectious diseases. Some people say this is due to the over-use of too-potent antibiotics, which eliminate protective infecting agents. Others believe it might be the widespread use of vaccines. There are even conspiracy theorists who believe they may be the results of terrorist acts or leakage of viral mutants from research laboratories.
Whatever the cause, globalisation and the increasing availability of long distance flights – Shanghai to Toronto for example – is making the spread of infections around the world much easier.
In the 21st Century we have already identified a number of infectious organisms that can and will present a major problem to patients, physicians, health care workers and administrators the world over.
With MRSA now reported in the “Healthy Community” the writing is already on the wall. We need something that can take on these superbugsThese include MRSA, MDR Tuberculosis, VRE Vancomycin resistant enterococcus, VRSA – Vancomycin resistant Staphylococcus aureus, VISA and GISA (Glycopeptide intermediate resistant Staphylococcus aureus). All these have proven to be sensitive to allicin and a sixth, PRSP Penicillin resistant Streptococcus pneumonia, although not yet tested, is very likely to be.
With MRSA now reported in the ”healthy community” the writing is already on the wall. We need something that can take on these superbugs. We need to reduce our dependence on pharmaceutical antibiotics, or at least make them more effective, by reducing the extent to which they are used.
Infectious disease is a big killer than heart disease or cancerBy not doing that, these powerful microbes will take over. Already infectious disease is a bigger killer than heart disease or cancer. The species above cannot be treated by anything the pharmaceutical industry has to offer – even the latest antibiotics, yet to reach the market, are unable to kill certain species of bacteria. We have seen international panic over SARS and MRSA spreading. This is bad enough but it is really quite worrying when you realise that doctors routinely encounter organisms like E. coli, Helicobacter pylori, Tuberculosis, Herpes virus, Acinetobacter, Cryptosporidium, Campylobacter, HIV, Salmonella, Cholera, Streptococcus Pyogenes flesh eating bacteria and others that are becoming multi drug resistant.
It is estimated that the number of bacteria, virus and fungal pathogens to be found either in or around every human being is so large as to be virtually infinite. This is why still, after 70 years of producing pharmaceutical antibiotics, recent surveys indicate that 90 percent of visits to doctor’s surgeries are infection related. It is also why more than one million metric tons of antibiotics have been dispersed into the biosphere in the past 50 years – half for human use and half for animal use which means that the indigenous bacteria of all living species are richly populated with resistant bacteria that we cannot get rid of. Is it any wonder that public health physicians are worried?
Why are we losing the battle?
Recent reports indicate that bacteria may send messages to each other about resisting antibiotic poisoning (Medicine Today, June 2002). In fact, bacterial signalling is going on all the time, all over your body, but especially in your mouth and guts. Finding ways of interfering with this signalling process is the latest objective of researchers who are waging the antibiotic arms race.
Recent reports indicate that bacteria may send messages to each other about resisting antibiotic poisoning (Medicine Today, June 2002)A major result of these bacterial conversations are bacterial communities! Among the more extraordinary sights visible through the latest confocal laser scanning microscopes, which allows objects to be viewed almost in 3D, are what have been dubbed ”slime cities” – armoured defensive communities where bacteria live and reproduce, safe from antibiotics, your immune system and other predators.
Known technically as biofilms, they are at the root of some of our intractable conditionsKnown technically as biofilms, they are currently the target of intense research because it is becoming increasingly clear that they are at the root of some of our most intractable conditions. The American Centres for Disease Control and Prevention estimate that 65 percent of human bacterial infections involve biofilms. Not only are they responsible for tooth decay and gum disease but they also cause many of the problems associated with cystic fibrosis, ear infections and infections of the prostate gland and the heart. They cause an estimated $6 billion a year of expenditure in the USA by causing hard-to-treat infections on catheters, artificial heart valves and other medical implants.
Similarly, irrational prescribing causes over-use of the very agents used to remove these infectious organisms. It is estimated that every year in the States, 10 million adults seek treatment for acute bronchitis and most are given antibiotics, even though the pathogens involved in most cases are viruses, which antibiotics aren’t designed to work on.
We tend to think of bacteria as primitive single cell creatures, but when they are organised into a biofilm they differentiate, communicate, cooperate and deploy collective defences against antibiotics. In short, they behave like a multicellular organism.
When bacteria organised into biofilm, they believe like a multicellular organismIn fact, bacteria from biofilms were among the first ever to be seen through a microscope when pioneer Antony van Leeuwenhoek looked at plaque – a biofilm – scraped from his own teeth in the late 1600’s. But it wasn’t until the 1970’s that scientists began to appreciate just how complex these micro slime cities are. Plaque, for instance, is founded on a base of dense opaque slime about 5 micrometres thick. Above this, vast colonies of bacteria shaped like mushrooms or cones rise to between 100 to 200 micrometres.
Enclosed within their highly effective defensive wall of slime live communities of a variety of bacterial strains. One researcher described them thus: ”The ‘cities’ are permeated at all levels by a network of channels through which water, bacterial garbage, nutrients, enzymes, metabolites and oxygen travel to and fro.
“The bacteria inside a biofilm, comprising 15 percent bacterial cells and 85 percent slime, are 1000 times less likely to succumb to antibiotics than bacteria in free-floating state”The notion that bacteria can talk to each other was first proposed more than 30 years ago by scientists studying ”glow in the dark” bacteria, such as Vibro fischeri, that live in the specialised ”light organs” of certain squid and marine fish. The bacteria don’t glow as individuals swimming freely, but when enough of them form a group, their illuminations are switched on. So they must have some way of letting each other know when enough of them have gathered. However, it wasn’t until the 1980’s that researchers identified the chemical they each put out – AHL (acyl-homoserine lactone). The more of them there are in one place, the higher the level of AHL. Above a certain threshold the concentration of AHL triggers the luminescence, in a mechanism usually referred to as Quorum Sensing.
But gradually a better understanding of just how biofilms fight off antibiotics is emerging. The bacteria benefit from pooling their effects. For instance, in a biofilm some bacteria can produce an enzyme that inactivates the antiseptic hydrogen peroxide, but a single bacterium can’t make enough to save itself. Another factor is that even if an antibiotic does get through and kill off some bacterial inhabitants, a substantial number are likely to survive. This is because bacteria exist in a spectrum of physiological states from rapidly growing to dormant. Antibiotics usually target some activity like cell division, and that means that the dormant ones will usually live to fight another day.
Dr Richard Novick has found that Staphylococcus aureus can be divided into four different types, each with slightly different signalling molecules. The molecules used by one type stimulated activity in its own group but inhibited it in the others – an example of the way bacteria compete with each other. This particular bacterium is a worry to virtually every health-care establishment in the Western World as it has developed a number of strains that are resistant to all pharmaceutical antibiotics, even Vancomycin, a toxic parenteral drug usually reserved as a last resort.
Bacteria are sufficiently well organised to be able to find ways of avoiding the immune system. For instance, in Vibrio cholerae, the bacterium that causes cholera, the same genes involved in regulating quorum sensing also turn on the toxin production (Proc Natl Acad Sci, 5 March 2002). The value of this strategy is that a few toxic bacteria might alert the immune system and be rapidly engulfed. By waiting to turn on toxicity until there are enough of them, they have a better chance of overwhelming the host’s defences.
‘It has been estimated that 40 percent of proteins in bacterial walls are different in “slime city dwellers” from those that are “free ranging”. The implication of this is that some of the proteins identified in cultures and targeted by antibiotics simply aren’t there in the city dwellers”Most of the work on quorum sensing has concentrated on chemicals that allow members of the same species to talk to one another. However, while Dr Bonnie Bassler at Princeton University was working on the luminous bacteria that led to the finding of quorum sensing in the first place, she made the remarkable discovery that signals from other bacteria could also turn on their lights. It seems that bacteria have some sort of Esperanto – a common language (Nature, 31 January 2002) – which involves a protein known as A1-2. Exactly what this system is used for isn’t clear yet. However, among the bacteria that infect humans, those found to produce A1-2 include Escherichia coli (food poisoning),Haemophilus influenzae (pneumonia and meningitis),Helicobacter pylori (peptic ulcers), Yersinia pestis (bubonic plague) and Staphylococcus aureus (pneumonia, meningitis and toxic shock syndrome).
“All of these bacteria can be killed by low concentrations of Allicin”Allicin, mother nature’s defender, is an agent that can break up a biofilm, destroy a wide range of bacterial species, wipe out fungal infections, boost an under active immune system, reduce cholesterol and blood pressure levels, prevent viral infections, kill off parasites, remove protozoal organisms, vasodilate when necessary, prevent the release of histamine, and even prevent mosquitoes from attacking – yes all of this from an agent that can be produced from fresh garlic!
Work is currently underway, using the latest technology, to allow us to blast apart a bacterial cell and detect exactly which proteins and enzymes it can produce. Then the same species is treated with allicin liquid or powder, blasted apart again and analysed to see which proteins and enzymes have been disabled and which, therefore, are inactive and unable to infect us. We already know that allicin is capable of penetrating bacterial cell walls and preventing the release of many enzymes that are toxic to humans. Allicin formulations are also effective against a wide spectrum of bacterial species, viral infections, fungal and protozoal disease as well as a large number of parasite problems.