Microbes’ Weapons and Protective Armour
Protection strategies
Our body employs two different strategies with respect to defending itself against potential harm caused by microbes, i.e. bacteria and fungi, present in the environment.
- Internal regions not in direct contact with the environment, e.g. the blood and brain:
The immune system keeps these areas sterile, i.e. all microbes are removed. - External areas in direct contact with the environment, e.g. the skin and gut:
It is not possible for the immune system to keep these areas sterile. Instead, it works in synergy with selected microbes to protect our body against the microbes that can be dangerous to us.
The Microbiome
Over 1000 different species of bacteria live on our skin and they extend from the surface and down into the deeper dermal layers. These together with fungi, viruses and mites make up the skin microbiome. The microbiome is individual to each person, it varies in composition across different locations on the body, and it is influenced by a large number of external and internal factors. The presence of these organisms helps to protect us, e.g. by producing biofilm which protects our skin. Studies have found that several disease conditions are associated with abnormalities in the skin microbiome, e.g. it was recently discovered that the chronic skin disease Hidradenidis suppurativa is associated with a lack of bacteria and biofilm on the skin (Ring et al. 2017) and that people with diabetic foot ulcers have a reduced variability in their microbiome (Gardiner et al. 2017).
However, not all bacteria and fungi are beneficial and their presence therefore needs to be governed, supervised and controlled by the immune system. In this respect, there are three main factors to consider:
- If microbes encounter an empty space, they will seek to colonise it.
- Some microbes are always dangerous to humans and need to be removed, e.g. Anthrax.
- Other microbes are only dangerous if they gain a dominant position, e.g. Staphylococcus aureus.
Our immune system therefore aims to ensure that all body surfaces in direct contact with the environment are populated by
- microbes that are non-pathogenic (not intrinsically disease causing)
- a mix of many different species.
These will keep each other at bay and, consequently, prevent anyone, benign in low numbers, suddenly becoming dominant and pathogenic (disease causing).
New RNA/DNA sequencing techniques have made it possible to identify most of the organisms present in a wound. With this new technology, it has been realised that the usual techniques of measuring the wound colonisation only identified around 5% of the organisms present, whereas new technology has increased the number to an estimated 85%. Using these new techniques, it has been possible to map the distribution of microbes across the body and the layers of the skin, and this has resulted in an enormous amount of new data. The probem, however, is that nobody knows how to interpret these findings, e.g. the relevance of changes in the microbiome during wound healing, what a “normal” microbiome is, what should be the target of a possible treatment etc. Most of the research at this stage is therefore mainly descriptive and it will be some time before it progresses towards targeted manipulations of the microbiome in order to understand how it actually functions.
Wound colonisation
The generation of a wound means opening up a new uninhabited area, which begs for microbial invasion. There will be microbes present on and in the skin, which are already accepted by the person’s immune system and which rapidly can invade the area. This will help to reduce the risk of invasion by pathogens, but it necessitates that the immune system is in control and can determine the proportion and distribution of the individual microbes to prevent a specific species of microbes from becoming dominant and out-of-control, as this would lead to an infection.
In burns, all or most of the microbes in the deeper structures and the surrounding skin will have been killed, which means that there is not a pool of microbes acceptable to the immune system that can invade the area. This increases the risk of undesirable organisms gaining a foothold and can explain why burns are so susceptible to infection.
In either case, it is clearly very important that the immune system is able to control the microbiome.
Wound healing
The natural wound healing process is normally divided into 3 phases:
- Inflammatory Phase (response to injury) – Immediate to 2-5 days
- Proliferative Phase (tissue regeneration) – 2 days to 3 weeks
- Maturation Phase (improving strength) – 3 weeks to 2 years
It is during the inflammatory phase that microbes and dead (necrotic) tissue are removed in preparation for the generation of new tissue to fill up and subsequently close the wound – which will occur during the proliferative phase. It is therefore important, that the immune system is able to govern, supervise and control the wound from very early on in the process to prevent the development of infection.
In cases, where the immune system lost the battle for control, infection or critical colonisation will develop as a result and the wound will usually remain stuck in the inflammatory phase or alternating between the inflammatory and proliferative phases.
In order to get the wound to heal, it now needs help to put the immune system back in control. Once this happens, the healing process will proceed normally and the time to wound closure will be more or less constant (Thomas 2006) as shown schematically below.
Factors influencing wound healing
Infection or critical colonisation
The older the wound, the wider and the deeper the infection will have had the time to spread. This process of spreading and becoming increasingly firmly embedded in the affected tissues can continue for years, leading to an extensive penumbra, i.e. an affected region around and underneath the actual wound. The longer the process has been on-going (months – year – several years), the more difficult it becomes to re-establish a microbiome that allows for healing to proceed and the longer the healing process will often take. The healing process, once it starts, is usually visible by regular deposits of mucky waste on the wound surface as this is the only place the body can dispose of the waste originating from tidying up the penumbral area. Finally, it is not unusual that old wounds ache when the restoration process is being undertaken.
Old wounds
The older the wound, the wider and the deeper the infection will have had the time to spread. This process of spreading and becoming increasingly firmly embedded in the affected tissues can continue for years, leading to an extensive penumbra, i.e. an affected region around and underneath the actual wound. The longer the process has been on-going (months – year – several years), the more difficult it becomes to re-establish a microbiome that allows for healing to proceed and the longer the healing process will often take. The healing process, once it starts, is usually visible by regular deposits of mucky waste on the wound surface as this is the only place the body can dispose of the waste originating from tidying up the penumbral area. Finally, it is not unusual that old wounds ache when the restoration process is being undertaken.
Osteomyelitis
Osteomyelitis (bone infection) can ensue as a result of an infection on top of a bone. Osteomyelitis is very difficult to treat and needs surgical intervention. If osteomyelitis has developed, the wound on top cannot heal. The microbes causing the infection in the bone generate waste and this must be able drain to the surface. The wound serves as the area of waste disposal.
Underlying diseases
The presence of underlying diseases in the tissue can cause the emergence of a wound, e.g. cancers, or impair healing and, consequently, lead to a wound growing in size or severity, as e.g. can be the case in diabetes.