We’ve all heard of the “flesh-eating” bacteria. It sounds scary doesn’t it? It is scary, but not in the way you’d expect. To put it simply, the bacteria don’t actually eat you… YOU eat you. That probably doesn’t make a whole lot of sense as I’ve just explained it… Necrotizing fasciitis (as it’s properly called) is most frequently caused by a bacteria known as Streptococcus pyogenes.

Even a relatively minor abrasion can lead to infection if the bacteria is present. All the action takes place in the Fascia, a layer of connective tissue and blood vessels covering the muscle. The bacteria multiplies like any other, but this is the twist. The strains of S. pyogenes capable of causing necrotizing fasciitis produce a super-antigen.

So what’s a super antigen? It’s a regular antigen but super But really… your immune system recognizes foreign material as “antigens”. Each T-cell and B-cell recognize only one antigen.

This specific antigen can be a part of the bacteria itself or something they secrete. This interaction is usually specific to the T-cell and causes them to become activated. T-cells then direct the immune response through the release of cytokines. Cytokines then activate other immune cells and attract them to the infected area. On average, an antigen activates 1 in 30,000 T-cells.

A super-antigen is not specific to a particualr T-cell. Rather, it simply binds (very strongly) to most T-cell receptors. This activates them just as if they had encountered their specific antigen. This process activates 1 in 5 T-cells… waaaaaaay more than should be activated. With all these cells secreting cytokines things get … confused.

You have immune cells called macrophages. These cells are what actually cause the damage. These are normally activated by T-cells. They phagocytose (take in) pathogens and destroy them. They have the ability to use oxygen radicals to kill these pathogens. With all those T-cells releasing cytokines these macrophages become over stimulated. They begin over producing oxygen radicals and bathe your tissues in them. This causes massive cell death and necrosis.

The treatment for necrotizing fasciitis is straight forward: surgical debridement. ALL the infected tissue must be removed to stop the infection. This often means removal of limbs. If the infection is not on an extremity the options are somewhat limited. Due to the extensive thrombosis caused by the infection antibiotics cannot reach the site of infection very well. The wounds can be irrigated with antibiotic solutions… but this is often ineffective.

This is a truly terrifying disease. Your own defences are turned against you in a matter of hours. The tissues are not really “eaten” but rather destroyed. The very cells meant to protect you can cost you your life.

Several studies recently have examined the mechanisms by which UV radiation causes immunosuppression.  The immune system in the skin relies on a specific class of dendritic cells known as Langerhans cells. When an antigen (i.e. a bacterium) is present in the skin these cells phagocytose and process the antigen. It is then presented on cell surface receptors. The Langerhans cell will make its way back to a Lymph node where it can activate T-cells. These T-cells then direct the immune response against the antigen via the release of cytokines.

Much in the way of specifics in this situation are as yet unknown. However, it is relatively certain that the process starts with the absorbtion of UV radiation by “chromophores” near the surface of the skin. In this case DNA as it in a known chromophore for UV radiation. This causes damage to the nucleic acid. When this damage occurs in immune cells there is a marked decrease in immune system function in that area.

The usual way to test for immune function in the skin is to use Contact Hypersensitivity. A simple antigen known as a “contact sensitizer” is introduced under the skin. After an immune response has had time to occur the contact sensitizer is presented again. In a normal immune response there will be an inflammatory response. In instances where there had been reasonable UV exposure the inflammatory response is not as strong. This indicates a weakness in the immune system.

The mechanism by which this nucleic acid damage causes immunosuppression is still questionable. The current theory is that these damaged dendritic cells produce cytokines that favor the activation of Th2 type T-cells. These are not as well suited for dealing with Hypersensitivity responses and cancer. Research also shows that these damaged dendritic cells have a tendency to stimulate suppressor T-cells. These cells release IL-10 which suppresses cellular immunity.

The consequences for this are great. All signs point to the fact that this mechanism can increase one’s risk of developing skin cancer. In a study from 1990 nearly all of those participants who demonstrated no suppressed contact hypersensitivity could be made to do so with exposure to UV radiation. In those with histories of melanoma the effect was universal. Clearly there is a connection.

Additionally it was found that contact hypersensitivity could be suppressed in people that were both “darker-skinned” and “lighter-skinned” if the UV dose was such that it could cause burning of the skin. If the dose was lowered to levels that would not cause a burn, the lighter skinned individuals had much more susceptibility to immune suppression.

The potential also exists for this process to affect infectious disease and vaccination. These findings are based largely on rodent models. Many infections have been shown to be more severe in UV exposed animals. Observation of human disease has yielded some interesting results though. The Netherlands has reported a seasonal change in the number of cervical smears positive for human papiloma virus. There is a positive correlation between the number of positive tests and the amount of UV radiation.

This is a very interesting process but requires further study. For instance, what is the role of vitamin D in immunity? Some studies indicate that vitamin D interferes with dendritic cell maturation. The future may well bring surprising discoveries in this area.

It has been illustrated that the human immune system can benefit from certain plant and bacterial substances. While the mechanisms are not yet known there is a great deal of research being done on this. Some studies seem to indicate clear benefits but others show none at all. Still others warn of possibly dangerous side-effects.

These “non-medical” treatments are divided into two categories. Probiotics are live organisms (usually bacteria) believed to benefit mucosal and systemic immunity. They are also believed to benefit the balance of microbial flora in the digestive tract. Most of these probiotic organisms are lactic acid bacteria of the genuses lactobacillus, streptococci, and bifidobacteria. Nutraceuticals are defined as a food or part of a food that is intended to provide beneficial health effects. In practice it usually means a supplement with the beneficial substance in a concentrated form. Efforts to determine the mode of action of these concentrated substances have so far been unsuccessful.

One infection in which probiotics and nutraceuticals have been studied is Helicobacter pylori. H. pylori is known to contribute to the development of peptic ulcers and gastric cancer. The standard treatment for this infection is combination antibiotic therapy. The use of multiple strains of lactobacillus was able to attenuate the growth of H. pylori in vitro. However, using probiotics and nutraceuticals in a clynical setting have been hit and miss. Some success has been seen with the use of sulforaphane an isothiocynate common in broccoli sprouts. This substance seems to inhibit the growth of certain strains of H. pylori as well as prevent the resulting gastric tumors.

It has been set fourth that probiotics may be able to treat irritable bowel syndrome (IBS). Currently treatment focuses on treating the symptoms themselves as opposed to the disease. Two recent studies using probiotics have been undertaken to study this possibility. The first used eight different probiotic species. They found that no difference was made in the symptoms of IBS. The second study found that treatment with B. infantis actually did decrease symptoms in most patients.

Encouraging results have been obtained in the treatment of C. difficile related diarrhea. Review of the data indicates there is an odds ratio of .37 in favor of probiotic treatments over placebo. One study found that treatment with Saccharomyces boulardii was able to prevent further infection by C. difficile in individuals prone to the infection.

It is known that problems with the gastrointestinal flora is a contributing factor to inflammatory bowel disease (IBD). Included in this class of illness are Ulcerative Colitis And Crohn’s Disease. One study tracked the use of E. coli Nissle 1917 against the common treatment of mesalamine. The results showed no difference between the two groups so it was assumed that the E. coli was as effective as the standard treatment. A second study seemed to confirm these results. However, another study showed that E. coli Nissle 1917 is no better than a placebo at prolonging remission. A separate study gave patients BIFICO capsules containing Lactobascilli, Enterococci, and Bifidobacteria. In this case remission was significantly improved over the placebo. Lab tests indicate that they had much lower levels of inflammatory cytokines than patients on the placebo.

Probiotics effect on Crohn’s Disease has not been studied sufficiently at this time to establish its effectiveness. Trials of both E. coli Nissle 1917 and L. rhamnosus showed no effect on the symptoms or continued remission if the disease. Omega-3 fatty acids have also been proposed as a possible treatment but initial results are not particularly encouraging. Early studies had positive results in the use of fish oil to prolong remission of Crohn’s Disease. More recent studies indicate that such treatments may be acting as adjunctives rather than a true therapy.

While it does seem that probiotics and nutraceuticals hold promise, more work is needed. In some cases clear benefits are observed but the danger is that people will forgo medical treatment in favor of probiotics. As these substances are not tightly controlled there have been cases of contamination by harmful bacteria as well as heavy metals and pesticides. There is not even any guarantee that a particular supplement has the substance it advertises. As time goes on we may see better studies that will focus on the effects of single strains of bacteria that will hopefully lead us to the most therapeutically useful ones. For now the jury is out on the usefulness of this therapy.

There are many factors making human space flight a complicated endeavor. Now, there seems to be yet another problem to be dealt with. Research indicates that many pathogenic organisms become more virulent in a microgravity environment. They can replicate faster and show increased antibiotic resistance. If long term space flights are to be a reality this problem must be solved. This phenomenon may also help us understand the mechanisms of bacterial resistance and allow the advent of new treatments.

Though it is unclear if astronauts experience immunosuppression there are many possible causative factors. For instance radiation, weightlessness, altered nutrition, and co-existence in an isolated confined environment (ICE). This is only part of the danger. Low gravity environments also seem to be conducive to the growth of the bacteria themselves. Studies in both space and simulated microgravity environments indicate that bacteria can develop increased stress resistance and virulence. These terrestrial experiments are needed because there are so few opportunities to experiment in space itself. There are also several other factors that relate to the problem of microbes in space. These include the absence of hydrostatic load, reduced shelf-life of drugs, and micro-flora exchange among crew members.

Studies done on bacteria grown in space show that they often have decreased lag phase and thus a higher final cell population. Several decades of research also indicate that they develop antibiotic resistance while in the low gravity environment. These resistant traits are not retained upon return to Earth. The mechanism for this is currently unknown but much attention is focused on it.

A study done on five cosmonauts indicated that they had exchanged intestinal microflora during their mission. These organisms accumulate antibiotic resistant properties from the normal flora of the digestive tract. Similar results were obtained from the Apollo and space shuttle missions. Opportunistic pathogens have been found on both the ISS and Mir. This proves that the possibility of infection due to the exchange of microflora and immunosuppression is a real one.

Several studies done on bacteria in simulated micro-gravity illustrate some interesting points. Salmonella enterica grown in a micro-gravity environment showed both decreased necessary dose and time to death in mice. These bacteria were also resistant to acid, thermal, and osmotic stress. This allows them to survive longer periods of time in macrophages. Several studies are currently being done on this phenomenon, one of the on the ISS.

A series of terrestrial experiments using hind limb unloaded mice has produced expected results. The experimental mice showed decreased survival rates as well as decreased survival times. Another mouse experiment involved bacteria taken from three men living together in isolation for a year. The pathogenic organisms taken from them after this period showed increased virulence when injected into mice.

The hope is that the study of these properties of bacteria will give us critical insights into the development of antibiotic resistance in addition to allowing prolonged space flight. If new methods of controlling the emergence of resistant strains were found it would be a boon to humanity. Resistant organisms usually appear a few years after the introduction of a new antibiotic. Our current drugs are becoming obsolete. Since 1981 the rate of death from infectious disease has gone from 36 to 63 per 100,000 each year. Government funding has just recently begun coming back to antibiotic research. Originally, it was assumed that antibiotics would put an end to disease. Now the race is on to find new drugs.

By finding the solution to the space flight problem we may find new ways to combat microorganisms everywhere. With our current drugs loosing their effectiveness and many pharmaceutical companies spending their time on non-invasive disease the outlook is troubling. It is important that we work towards finding new methods of controlling microorganisms before the current generation of drugs become useless.

Correct protein folding is a basic element of biological function. Misfolded proteins cannot perform their intended function but are usually corrected by chaperone proteins. In protein misfolding disorders (PMDs) these irregularities are not corrected and the proteins aggregate causing disease. Noted PMDs are Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease, cystic fibrosis, and type II diabetes. There is also the well known subclass known as transmissible spongiform encephalopathies (TSEs). Among these are Bovine Spongiform Encephalopathy (“mad cow” or BSE), Scrapie, and Creutzfeldt–Jakob disease.

There is now sufficient evidence to support the theory that misfolding and aggregation of proteins is the basis for most PMDs. Abnormal protein aggregates are found in the tissues most damaged and accumulation of these aggregates is the accepted endpoint for PMDs.

We know that prion diseases (specifically TSEs) are transmissible. However, it took quite some time for the now accepted “protein only” hypothesis to gain a foothold. It seems to go against what we know about disease. These diseases involve the PrP gene which is found in all mammals. The normal cellular form of the protein is termed PrPc. A conformational change in this protein replaces many of the alpha helices with beta sheets. This modified form is called PrPsc. This protein seems to have the ability to cause disease by modifying PrPc creating more PrPsc. A study clearly showed that PrPsc is capable of modifying PrPc in vitro and that that infective PrPsc can cause disease when injected into hamsters. It should be noted that the hamsters were exposed to whole brain homogenate from the original sample so the purity of the sample cannot be guaranteed.

It is believe that these prion proteins begin catalyzing the conversion of PrPc like a crystal, producing long fibrils. These could eventually break into smaller segments either by mechanical force or an unknown enzymatic process. This is often referred to as the seeding-nucleation model and has become widely accepted.

It has long been in question if other PMDs can be transmitted like prion diseases. It seems that those who work with people suffering from PMDs do not have a higher chance of getting the disease themselves. However, the same is true for those who work with prions. The gestation period is also prohibitively long to study the effects of these factors. In addition to this limitation most PMDs are exclusively human diseases. Therefore, finding a suitable experimental model is difficult. Marmosets injected with brain homogenate from Alzheimer’s patients developed scattered amyloid plaques in a few months. However, it is not possible to guarantee that these were not all original plaques from the homogenate. A separate study failed to produce similar results in primates. Recent studies using transgenic mice expressing the human version of the amyloid precursor protein were injected with Alzheimer’s brain homogenate and developed significant amyloid plaques in several weeks. These mice develop plaques later in life by design so the true implications of this are questionable.

The best evidence for prion like activity in PMDs is in the case of systemic amyloidosis. In this disease an inflammatory response causes serum amyloid-A (SAA) protein to be deposited in various organs causing damage. This can be triggered in mice by eliciting an inflammatory response. The progression of the disease is increased dramatically with exposure to spleen or liver extract containing amyloid plaques. Additionally, study of mouse senile amyloidosis shows that oral administration of amyloid fibrils can cause the development of severe amyloid plaques.

With our knowledge of protein related diseases expanding rapidly some things we learn can be disconcerting. It may be possible for PMDs to be transmitted in some instances. Further studies are certainly required before any of them are labeled infectious.