Why are pathogens pathogenic?

Introduction

Pathogens are characterised by their ability to cause diseases in the host they are infecting (Alberts B, 2002). However, a large proportion of microorganisms close to pathogens are existing in symbiosis with their host and positively impact the good functioning of the host, such as particular strains of bacteria Escherichia coli found in the healthy gut (Khan et al., 2019). These melting pots of organisms exist everywhere within a microbiome and differ greatly from host to host depending on the environment, diet and genetic factors. Understanding the difference between pathogenic and non-pathogenic microorganisms and why pathogens are pathogenic is essential to help the host fight and recover from a disease.

The Basics

The main goals of any living organism are:

1. Survive

2. Proliferate (reproduce)

This applies to any members of the seven Kingdoms of life (Ruggiero et al., 2015), including microorganisms and pathogens such as virus, bacteria, fungi and parasites (Alberts B, 2002).

In order to survive, an organism needs access to several essential resources: a stable environment at the right temperature allowing for its metabolic functions to be active (often between 20 and 37°C, depending on the organism), nutrients, oxygen and water to have the energy to function and in the particular case of viruses, the molecular machinery of a host cell to replicate and assemble (Alberts B, 2002).

The Host

Pathogens have developed an efficient strategy to fulfil their needs: they colonize a host and live at its expense. However, this situation is often suboptimal from the host's point of view, which tends to develop mechanisms to fight the invader. Hosts have physical barriers, such as the skin, to protect them from the entry of pathogens. They also have an immune system, composed of a large variety of cells, each specialised in a particular aspect of the fight against the pathogen, once it has entered the host (Marshall et al., 2018). In order to survive, pathogens need to make sure they are not limited by the defence strategies of the host, even if the health of the host is then comprised.

Pathogenicity

Having a character 'pathogenic', also called pathogenicity, is the ability to cause disease. The symptoms of disease are either a direct consequence of the colonisation and replication of the pathogen or side effects of the immune system of the host, in response to the pathogen (Cann, 2016). In order to replicate, some pathogens, such as viruses, need to enter a host and multiply within a cell. Once they have completed this step, they need to exit the cell and find a new one, to replicate again. The exit process necessitates them to break the membrane of the host cell, which most of the time leads to the death of the host cell (Kaminskyy and Zhivotovsky, 2010). As a consequence, the host shows signs of injured tissue in the infected area, such as the lesions observed in individuals infected with the herpes simplex virus (Sen and Barton, 2007).

Immune Response

These lesions are a symptom of disease. In addition, the immune system of the host has developed highly specific receptors to recognise and detect pathogens called Pattern Recognition Receptors (PRRs) (Medzhitov and Janeway, 1997, Li and Wu, 2021). When this happens, the immune system creates an inflammatory environment around the infection to help recruit additional immune cells, to ensure a clear defeat of the pathogen. During this process, pro-inflammation cytokines are produced. These small proteins, implicated in cell signalling, are essential to ensure an adequate response of the immune system to the pathogen. However, some of the cytokines, such as Tumor Necrosis Factor (TNF) and Interleukin-1 (IL-1), are produced at high levels and are responsible for the onset of fever in the host, which is a symptom of the disease.

Types of Symbiosis

Based on these observations, it appears that the pathogenicity of a pathogen is only a direct consequence of its wishes to survive and proliferate. However, many microorganisms are non-pathogenic and are known for their symbiotic relationship with their host. In that situation, both the microorganism and the host benefit from the interaction. Commensal bacteria located in the gut of the host have recently been considered essential in the protection against harmful pathogens (Khan et al., 2019, Stecher, 2015). Bacteroides acidifaciens even seem to protect from metabolic disorders such as obesity (Yang et al., 2017). The symbiotic strategy developed by commensal microorganisms allows them to survive in the host for as long as the interaction stays beneficial or the host lives. However, their proliferation is limited by the physical space allocated by the host to them. Their proliferation cannot be infinite.

Research shows that the difference between pathogenic and non-pathogenic bacteria lies in their genes: the pathogenic bacteria have acquired virulence genes, which encode for virulence factors responsible for the disease (Kaper et al., 2004), such as toxins from Vibrio cholerae, the bacteria responsible for cholera (Faruque et al., 2003). The virulence genes have usually been acquired from another pathogenic bacteria or a virus and have one main purpose: to help the pathogen survive or proliferate. The cholera toxin induces a change in ion balance in the host, leading to diarrhoea, the most common symptom of cholera disease. Although life-threatening for the host, the loose, watery stools ensure the further dissemination of the bacteria (Faruque et al., 2003) and the fulfilment of its main goals: survival and proliferation.

Conclusion

The mechanisms explaining the pathogenicity of pathogens are still not fully elucidated. However, recent progress allows us to better understand how pathogens survive and proliferate and what makes them pathogenic.

It clearly appears that the main goals of pathogens are to survive and proliferate. To fulfil that purpose, they have developed ingenious strategies to acquire the necessary resources and disseminate them in the environment. They infect a host that can meet their requirements and, once they have multiplied enough, they utilize the host to spread.

In summary, our literature research shows that pathogens are pathogenic to survive and proliferate without the obvious mean of being detrimental to their host. Their virulence factors have been developed for that purpose and are unfortunately a cause for the symptoms of disease in their host.

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