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"The presence of a pathogen does not necessarily indicate the presence of disease."
You will have no doubt heard us say that.
Enter 'Virulence Factors'. These help us discern how pathogenic a microorganism is. It is another piece of information we can use, along with the host immune markers, and symptoms, to better understand the state of play in that never-ending ‘dance’ we are in with our microbial inhabitants.
You may have noticed markers such as 'babA', 'stx1', 'Toxin A', 'virD', 'LT/ST', etc. on your GI-MAP reports, and we can gain a good idea of the level of LPS by looking for elevations in Gram-negative bacteria. These are all virulence factors.
What are Virulence Factors exactly?
Bacteria, viruses, fungi and protozoa are driven to survive and reproduce, just like we are. This creates an inherent conflict. Our immune systems are well-equipped – when functioning optimally – to keep the balance. To maintain that synergistic homeostasis, but slightly in our favour, of course. Just as we have evolved to keep the peace and a slight stronghold, so have our microorganism inhabitants.
Virulence factors are produced to enhance a microorganism’s capacity to cause disease. They refer to the properties (i.e., gene products) that enable better establishment on, or within, the host. These include bacterial toxins, cell surface proteins that mediate bacterial attachment, cell surface carbohydrates and proteins that protect a bacterium, and hydrolytic enzymes to aid cell invasion.
Ultimately, they help the microorganism to:
- Enter into/out of cells
- Obtain nutrition from the host
In a nutshell, virulence is the measure of the pathogenicity of an organism. The degree of virulence is related directly to the ability of the organism to cause disease despite host resistance mechanisms.
The virulence factors can be divided into a number of functional types, which help achieve the above:
- Adherence factors: especially helpful to colonise mucosal sites, typically by using pili (fimbriae) to adhere to cells.
- Invasion factors: surface components that allow the bacterium to invade host cells
- Capsules: these protect microorganisms from opsonisation and phagocytosis
- Endotoxins: the lipopolysaccharide endotoxins on Gram-negative bacteria can cause fever, changes in blood pressure, inflammation, lethal shock, and many other toxic events
- Exotoxins: these include several types of protein toxins and enzymes produced and/or secreted, such as cytotoxins, neurotoxins, and enterotoxins
- Siderophores: these are iron-binding factors that allow some bacteria to compete with the host for iron, which is bound to haemoglobin, transferrin, and lactoferrin
A microorganism can possess a wide array of virulence factors. They may only express these virulence factors when in the presence of certain other microorganisms, or in a particular environment, such as a highly inflamed one.
Some are chromosomally encoded and intrinsic to the bacteria (e.g. capsules and endotoxin), whereas others are obtained from mobile genetic elements like plasmids and bacteriophages (e.g. some exotoxins). Virulence factors encoded on mobile genetic elements spread through horizontal gene transfer, and can convert harmless bacteria into pathogens, otherwise known as ‘accessory pathogens’.
It is a complex picture. A dance for survival both inter- and intra-biome. That being, there’s a dynamic relationship between host and microorganism, as well as microorganism and microorganism.
We use quantitative measures of virulence factors and of certain microorganisms, together with host markers as a ‘window’ into our internal ecology.
It is all interdependent. A great waltz. Or sometimes a mosh.
Or sometimes a crowdsurf, and we are just being taken along for the ride.