close
The amazingly collaborating network of bacteria or the double-edged sword of antibiotics
IMG_4767
Antibiotics destroy, they don’t cure

Just recently I have been confronted with guys suffering from infections with troublesome bacterial strains like Pseudomonas, a microbe usually only afflicting people with a weak immunity, and people in critical care hospital units. Obviously, the majority of us still thinks that antibiotics are curing  agents. Antibiotics are destructive agents, the destroy bacteria in the best case. Many strains today evade the targeting by antibiotics. What you need to get fit or survive is a strong and balanced immunity that takes over curing after destruction. Biestmilch should be the agent of choice supporting immunity and the healing process.

Is therapeutic success perhaps due to luck rather than to good judgment

Serious infections and antibiotic resistant bacterial strains dangerously spread. Antibiotics are carelessly prescribed and turn thus less and less effective. In my opinion this topic and its many discourses entangled with it leave us behind with a lot of misconceptions, uncertainty and ignorance. Antibiotics resistant species and strains of bacteria became one of the major threats in curing infections in the hospital environment, and are spreading into the communities, examples are tuberculosis and Staphylococci infections, Escherichia coli, Salmonella enterica, and Klebsiella pneumoniae.

The following article picks up some interesting aspects of the very recent scientific knowledge, only in brief and only in fragments, because the topic is huge, and can easily fill books’ pages. I want to outline the current status quo and future visions based on todays views. This should be our concern, because each of us could one day be a victim of this development.

In community medicine antibiotics are still the quick and easy fix

Even though, it seems that the awareness of the dangerous development of treating resistant bugs successfully is wide-spread, and talked about a lot by physicians, biologists and media, reality reflects otherwise. Whenever a physician feels insecure about a patient’s symptoms that he assumes are related to a microorganism antibiotics are in quick and close reach. A sore throat, a severe cough lasting for some days, and here we go, the prescription for an antibiotic is quickly written, and doctor as well as patient feel safe.

Patients nowadays are not patient enough anymore to give the body the time for healing. This is of course not only their fault. Our fast moving society often doesn’t allow us to stay home for a week, the time it mostly needs to recover from an acute (in most cases virus) infection. The ability to assess the risk, the ability to interpret body signs and take action accordingly got lost in many ways. Fever turned into a phenomenon that scares people, lungs became scary monsters that people are afraid may affect the heart. Joint pains may be suspicious of a rheumatic disease etc. etc…

Unfortunately, the knowledge our ancestors about what to do in cases of acute infections got almost lost. Moreover, many of us prefer to hand over the responsibility to the doctor.

Therefore we go and see the doctor for illnesses that usually disappear by itself and don’t need medical treatment. At the doctor’s two fears collide. Ours, we don’t want to die and the doctor’s, he doesn’t want to make a mistake and disappoint the patient or even get sued. In this setting antibiotics became a quick and efficient fix.

The dilemma starts where antibiotics are not seen as chemical compounds that are active in a bacterium within a body and an environment

There is a profound misconception here. Therefore let’s put the definition antibiotic at the very beginning of this article. Any class of organic molecule that inhibits or kills microbes by specific interactions with bacterial targets, without any consideration of the source of the particular compound or class can be called an antibiotic. Thus, purely synthetic therapeutics are considered antibiotics.

The meaning of the word changed over the decades. Today common sense connects antibiotics and its meaning with an agent that is ridding us of bugs of all kinds. Back in the days of their discovery the term antibiotics simply described its use, its laboratory effect, or its activity as a chemical compound. The term antibiotic does not say anything about its mechanism of action.

Unfortunately, due to ignorance and fear antibiotics are administered neglecting its mode of function and its effects within the bacteria, the body and the environment. The interactions of the antibiotic, the targeted microorganism and the body are not part of the medical discourse between patient and doctor. The problem of the development of resistant strains is located somewhere outside, far away from the individual situation of the patient. Antibiotics are basically for the good of the patient. Rarely we are aware of the fact that these compounds are actively spread in our environment with the detrimental consequences of resistant bacteria and the emergence of a bacterial monoculture destroying the healthy balance of microbial diversity.

Antibiotics became an unquestioned therapeutic fact. The harmful sides of this medication seem to me to be a discourse that became completely disconnected from the patient’s and doctor’s actual therapeutic interactive environment.

Antibiotics interact with the metabolic pathways of bacteria while viruses interact with the cell and don’t respond to antibiotics

At this point we are right in the center of the misunderstanding. Far too many antibiotics are prescribed without differentiating between viral and bacterial infections. Antibiotics cannot interact with viruses, because viruses don’t have an apparatus for the biosynthesis of the molecules the antibiotics interact with. The virus needs a host’s cell to do this job for it. Viruses integrate themselves into a living cell. They can do this on many levels from the nucleus to the cell, to its membrane. The virus and its metabolites can take over the control of the cell and its metabolism, and change the cell’s dedicated function. Viruses replicate by using the cell synthesis machinery, then virus metabolites and viruses spill an organ, an organ system, or the whole body. An acute virus infection may be the apparent phenomenon.

Or, the virus does not succeed to conquer the cell immediately, but silently integrates itself into the cell, and may finally induce a mutation in the nucleus or a change in one of the many signaling pathways of the cell. This mutation or change can lead to optimizing the cell functions or it can on the long run be deleterious for the cell, the organ or the organism by inducing a chronic virus infection or contributing to the emergence of a tumor.

Bacteria are not good or bad per se, nor is hygiene, we need to see the environment

Now, back to the antibiotics that are intervening with the biochemical pathways of the bacteria. To understand the many problems we face today due to the irresponsible use of antibiotics we have to have a rough idea how bacteria tick and survive on this globes for trillions of years. Men and bacteria coexist in a symbiotic way ever since. Our gut contains more bacteria (more than 500 species identified until today) than our body got cells, and there are other mucosal linings colonized with bacteria that play an integral part in keeping our body in balance. Everybody got his or her very own microbial ecosystem. This means that my gut’s E. coli which is non-pathogenic for me, may induce an illness in you.

Thus bacteria play an essential role in our well-being. They may even be at the very beginning of more complex life, when cell fusions finally lead to complex organisms. Recent research discovered receptors on human cells that are either identical with bacterial elements or exactly mirror bacteria. These receptors make an essential part of our innate immune system by identifying bacterial components. It is well known today that our immune system displays patterns of receptors on immune cells that are able to recognize all common species of bacteria. This was a very brief outline of the positive aspects of bacteria, and now the negative ones, when bacteria turn against us.

Bacteria became almost synonymous with evil and dirty. This is not amazing, if we go back in history when thousands of people died from bacterial infections often at a very young age. We thought to have solved this problem after having discovered antibiotics. Everybody knows that this was not the case, and if we don’t take care, we may even fall back into the pre-antibiotic era.

Here it is the double-edged sword: hygiene was one of the biggest steps forward in making our health care systems working successfully, on the other hand this same hygiene is turning against us. The soil’s and the air’s microbial ecosystem drifted out of its balance. The balance among the many species and strains of bacteria controlling and constraining each other went berserk. Like in our flora we push the world of bacteria from diversity to monoculture. One phenomenon is the emergence of antibiotic resistant bacteria strains and species, another may be the increase in allergies and autoimmune diseases (another topic, another article!).

The realm of bacteria is a tightly interwoven communication network

The bacteria and their organizational principal accounts for many of the issues we have with antibiotics. We could have known better much earlier if our distortion field had not been so rigid. Only in the past few years has it been appreciated that gene exchange is a universal property of bacteria that has occurred throughout eons of microbial evolution. As mentioned already above, the discovery of bacterial gene materials in the nucleus of cells including those of humans gives strong evidence about the great importance of horizontal gene transfer in the evolution of the genome on the one hand, and the organization of the bacterial collective on the other.

Bacteria tightly connected and communicating
Bacteria tightly connected and communicating

The way bacteria are communicating with each other, how they are able to exchange genetic materials, and the fact that they are producing antibiotics and express antibiotic resistant genes themselves indicates that the problem of resistance is integral part of the problem when dealing with bacteria and antibiotics.

Obviously resistance was always there, perhaps it is a essential property for the survival of bacteria.

Accelerated emergence of resistance is the downside of one of the most valuable discoveries of mankind

Penicillin was discovered by Alexander Fleming in 1928, and in 1940, several years before the introduction of penicillin as a therapeutic, a bacterial penicillinase was already identified. Once the antibiotic was used widely, resistant strains capable of inactivating the drug spread. This phenomenon kicked off huge research efforts to find other compound that may evade cleavage by penicillinases. Only now, knowing what we know makes us appreciate and assess the value of the identification of a bacterial penicillinase before the use of the antibiotic. Recent findings confirm that a large number of antibiotic resistant genes are components of natural microbial populations. Are antibiotics and resistance an inseparable couple?

Let’s have a more closer look on these small creatures. Let’s not forget that they are alive and herewith possess their own genome and their own metabolic system that produces and secretes a large number of molecules, molecules of which we know only very little about. Bacteria possess pumping systems that prevent intracellular accumulation of molecules that may be able to kill or freeze them. The coexistence of synthesis and resistance functions in one and the same bacterium has been confirmed in recent studies. It seems logic to us that resistance is a mechanism of protection, an element of the bacterium that is needed for its chemical equilibrium.

It is a completely different story to look at bacterial monocultures in a lab or at bacteria in the wild

Only recently scientists started to study microbes in their natural environments. And it occurred what usually occurs when you leave the lab and have a glimpse on nature: you change your mindset and then your working hypothesis, and so it happened to the scientists observing bacteria in the wild.

They saw the large number of bioactive microbial compounds they produce, and found a lot of open questions they try to find the answers for now. Antibiotic activity was only one of the biological properties of the many bioactive small molecules. They exhibit extensive multi-functionality and most likely are involved in cell-cell signaling within and among the network of bacteria and other organisms in the environment (fungi, plants, insects, and even human and animal hosts). Researchers changed their path while investigating the interactions within complex bacterial communities (microbiomes) in different environments. They realized that many diseases occur as the result of polymicrobial infections, and they are working now on the implications of these observations.

If we look at the so-called resistance mechanisms from the standpoint of an antibiotic that lost its effects resistance gets a negative flavor. If we look at it from the perspective of a bacterium the process of “resistance” may facilitate cell-cell interactions, protect natural degradation pathways, or other functions we don’t know yet.

Some scary examples that should make us think when to use antibiotics or please, no antibiotics in cases of flu and common cold

Erythromycin was an early example. It was introduced as an alternative to penicillin for the treatment of Staphylococcus aureus in Boston City Hospital in the early 1950s. It was completely withdrawn after less than a year because 70% of all the S. aureus isolates were found to have become erythromycin resistant. The same was observed with a tetracycline and chloramphenicol and, subsequently, with other antibiotics.

Unfortunately, the colossal need for these valuable drugs has had a significant environmental downside. In the 60 years since their introduction, millions of metric tons of antibiotics have been produced and employed for a wide variety of purposes. Improvements in production have provided increasingly less expensive compounds that encourage nonprescription and off-label uses. The cost of the oldest and most frequently used antibiotics is (probably) mainly in the packaging, and this is really ironic, if we look back in history when pandemic infections stroke mankind.

What happened during the evolution of bacteria over several billions of years cannot be compared to the phenomenon of antibiotic resistance development and transfer over the last century. The existing processes of gene acquisition, transfer, modification, and expression that were in place ever since are expanding and accelerating in the modern biosphere. The way how bacteria exchange genes (plasmids, phages, and transformation) are well known from the lab. But in the natural environment other processes may exist. For example, bacterial cell-cell fusion might be favored in complex mixed microbial communities.

Another important point, we don’t know the pathway from an environmental gene to a clinical resistant gene yet. We can only assume that this road is easy to walk on for those genes.

One more practical remark for you, if you have to take antibiotics: Especially at sub-inhibitory concentrations, the process of antibiotic resistance development may be facilitated.

What could be done to slow down the detrimental signs of resistance development?

Over the years, many different solutions have been proposed by experts and all the major international health groups (e.g., WHO and the CDC). Among the proposals for action are strict controls of antibiotic use in humans. Here we clearly enter the territory of politics. I intentionally stay out of this area because here discussions never end, and the various agendas get blurry and disarrayed. I cannot contribute anything of influence that would really matter on a larger scale. I may only dare to advise you to question yourself before using antibiotics, and question it, if you feel the prescription was a doctor’s quick and easy pick.

Most infections are first of all of viral origin, then antibiotics are not justified. If you come down with an acute virus infection it takes you up to one week to recover. Fever shouldn’t scare you. A healthy circulatory system can easily cope with 39°C and a heart frequency over 100 beats for a week or even more. Homespun remedies are not part of this article, but play an important role. We should definitely rediscover and learn about the remedies of our ancestors.

If it comes to non-antibiotic approaches for the treatment of bacterial diseases, Biestmilch is a serious option stimulating or recruiting the innate immune system of the host. Recent advances in our understanding of the roles of the human gut microbiome in innate immunity underscore the role of Biestmilch as an other therapeutic option. At least you should consider taking it together with antibiotics. The debris antibiotics leave behind has to be cleaned up by the immune system. Biestmilch empowers the immune system to do so more effectively.

This is the end of a fragment on a very complex topic.

Literature
Hawkey PM, Jones AM: The changing epidemiology of resistance. Journal of Antimicrobial Chemotherapy, 64: Suppl.1, i3–i10, 2009
Davies J,  Davies D: .Origins and Evolution of Antibiotic Resistance. Microbiol. Mol. Biol. Rev. 74(3):417, 2010
Levy St B, Marshall B: Antibacterial resistance worldwide: causes, challenges and responses. Nature supplement, 10(12): 122-129, 2004

Susann

Susann

Susann is the biest prototype and head of the team. She is Austrian, has studied medicine, meaning she is a medical doctor and the Biesters' alpha wolf. Susann continuously produces new ideas, is strong in making concepts and is practically always ON FIRE. Without her BIESTMILCH wouldn't be where and what it is today, and anyway - not possible.

IRONMAN Frankfurt, welcome banquet 2015: Looking at things from a distance

Sam Gydé’s strategy to take Biestmilch