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Introduction of Virulence and Tuberculosis Case Study
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Tuberculosis or TB is a highly communicable air-driven disease that is caused by the pathogen Mycobacterium tuberculosis. Initially, TB affects the lungs of a person but in the later stages, they are likely to affect the functions of the kidneys, brain and the spine as well. In case of improper treatment, the cases might be fatal and its high communicable factor makes it an issue of concern. The primary symptoms of this disease include sick feeling, fever and occurrence of sweats at night. The physical changes that might occur are significant weight loss and fatigue and uninterrupted coughing with chest pain. The cough is likely to be blood containing in several cases and this symptom depends on the area of occurrence. In some people, TB might overcome the defense mechanism of the body and eventually multiply. The magnitude of infection will increase if treatment at the right time is avoided and this might lead to damage to the body tissues.
- Transmission, attachment/adherence and initiation of disease
The transmission of TB is air-based and the agents associated with this phenomenon of transmission are droplet nuclei. These droplets are produced when people are already affected with TB cough or sneeze. Any act that involves the spraying out of mucous from the body like spitting and singing produces these droplets. These agents are capable of staying in the air for a long time depending on the environment. Surface contact is not involved in the transmission of TB and this transmission only takes place when these nuclei travel through the nasal passage of another person. The bacterium in these droplets then travels from the passages to the “upper respiratory tracts” and then to the bronchi. They finally reach the alveoli of the lungs where they set camp and start approaching the other vital organs of the body.
Figure 1: Tuberculosis transmission process
(Source: Influence from the views of Bilal et al. 2021)
The above picture depicts that bacilli are transmitted through droplet nuclei. Tuberculosis affected people's coughing droplets consists of bacilli which are transmitted to a normal person. However, it has been found that the majority of people are not affected by tuberculosis because innate immunity pathogen plays an important role as antibody-antigen is developed in the body. Various gene polymorphism influences the adhesion of tuberculosis bacilli and the release of tuberculin in a host environment. As stated by Bilal et al. (2021), innate immune responses cause three results that prevent tuberculosis development which are cell necrosis, apoptosis and survival.
The environment plays a huge role in the transmission of this disease because this is solely air-borne and when placed in an air-tight compartment, it is likely to spread even more. Transmission from animals is there for this disease but they are likely to occur and the phenomenon of transmission is the same (Pourmiret al. 2018). The sneezing and coughing of any TB affected animal near a person can spread the disease. After the host has been colonised, “inflammatory cellular infiltrates” are triggered in these sites and in most cases it is the lungs where this takes place. Granuloma is formed after this that is made of cellular aggregates like “macrophages and multinucleated giant cells”. The initiation of this disease takes place when these phenomena occur simultaneously and the triggering points play a vital role in this. External factors like smoking and exposure to air pollution are contributing factors in this context.
Factors like substance abuse and health conditions like silicosis, diabetes and AIDS are likely to trigger the effect of TB. Cancers of the head and neck along with kidney diseases are like;y to influence this condition too. Alcohol addiction or malnutrition might be other contributing factors for which the person themselves are responsible (Milhem et al. 2021). External trigger points associated with TB that a person might not have control over are indoor air pollution and passive smoking. In case a person is exposed to passive smoking there are already chances of occurrence of TB and this chance doubles if the person smoking is affected with TB himself (Mirzaei et al. 2021). Minor infections of TB might not cause observable symptoms in a person and they can lead to higher risks in this case.
Infection and spread of Tuberculosis
(Source: Statista.com, 2022)
The bacteria of tuberculosis are spread through the air and also spread from one affected person to another person. Around 2 billion people are affected by Tuberculosis the World's total population. Moreover, approximately, 10 million people become actively ill with Tuberculosis disease (Statista.com, 2022). In the year 2019, nearly 1.2 million people are feeling ill with Tuberculosis Bacteria globally (Statista.com, 2022). In addition, around 465,000 people are getting infected with TB in the United Kingdom (Statista.com, 2022). From a survey in London, around 52 per cent of respondents are affected by TB (Statista.com, 2022). From different cases in the United Kingdom, several factors are rising because of TB. Those consist of increased migration of people from different areas Worldwide in which Tuberculosis is mostly common rather than in the United Kingdom.
The macrophages in the lungs engulf the MtB when it enters the human lungs and then it traps the bacteria within the phagosomes. Generally, these phagosomes would get attached to the lysosomes but the invasion of the bacterium prevents this and hence their destruction is avoided. Lysosomes would function in the destruction of Mtb bacterium but this phenomenon hampers that process. The TNT toxin plays a major role in the onset of the bacterium in this stage because the Mtb that cannot be destroyed grows safely in the phagosomes (Munansanguet al. 2022). Necroptosis takes place in this situation that makes the TNT toxin destroy the macrophages hence the immunity of the individual is diminished implying the onset of the disease.
Virulence factors of tuberculosis
(Source: Influenced from the views of Abbas & Abou Baker, 2020)
ESXI present in M. tuberculosis is the main protein that is responsible for virulence which translocates in host to cytosol from phagosome. Another antigen that causes virulence is an antigen named ESAT-6 which is an immunogenic protein. As stated by Abbas & Abou Baker, (2020), zinc and iron are essential for the growth of M. tuberculosis in the host body and some soluble factors are secreted by ESX3 which increase the uptake of iron and zinc in the cell and therefore, it is a virulence factor. On top of that HBHA and PE_PGRS are proteins which determine the extent of adhesion of M. tuberculosis in the cell wall.
Mtb exports several exotoxins and the first step of these toxins involve passing through the cytoplasmic membrane of the cells. A lot of steps are steps are involved in this mechanism that involves the secretion of these toxins. The molecular machinery associated with the secretion includes the functioning of a variety of bacteria (Li et al. 2018). As mentioned by Stefanescu et al. (2021), adherence refers to the sticking of the bacterial molecules to the walls of the cells and scavenging refers to the killing of other Immuno agents that might come their way. All the major pathogens including bacterial and viral follow several “toxin secretion mechanisms” although there are minor exceptions. Mtb bacteria generally follow the “type 7 secretion system” and the types that come under this category is “ESX Type 1, 2, 3, 4 and 5”.
There are two types of immunities that are evaded by M. Tuberculosis and these are the “Innate Immunities and the Adaptive immunities”. The evolution of the pathogen through thousands of years has enabled it to exist along with the presence of a fully functional immune system and cause infection to the host.
Innate immunity Evasion process
Receptors are composed of “Toll-like receptors (TLR)”, “C-type lectin receptors”, “NOD-like receptors”, “mannose rectors” and also the “complement receptors”. These receptors have been used for the purpose of recognizing M. Tuberculosis by the cells that are phagocytic in nature-oriented with the innate immune system (Alatawi&Alshabrmi, 2022). These receptors also aid in the initiation of the formation of pathways through the process of programmed death of cells, such as by causing Apoptosis. Moreover, some cellular mechanisms that are intricate have been developed by M. Tuberculosis which aid the pathogen in persisting within the macrophages. These include processes such as causing active blockade in the fusion process between mycobacteria and resident phagosome with the help of lysosomes and many more.
The survival of the pathogen is ensured through the process of inhibition caused by different pathways of the innate immunity system (Allen et al. 2021). Therefore the survivability of M. Tuberculosis is ensured by the process of pathogen clearance performed by the immune recondition system.
Mechanism of drug resistance in M. tuberculosis
(Source: Influenced from the views of Van Camp et al. 2020)
The above picture depicts that the drug resistance property increases the duration of a treatment course. Cell walls of M. tuberculosis act as a barrier and prevent drug entry in the prevention of drug efflux mechanism. In addition, various mycobacterial genomes also cause the inactivation of antibiotics through initiating hydrolysis, acetylation, phosphorylation and adenylation of various drug compounds. As opined by Van Camp et al. (2020), active protein also may efflux out the antibiotic drugs.
Adaptive immunity evasion process
The evasion process of the innate immune systems impacts the development process of Adaptive immunity. Moreover, the “Immunity mediated by the T-cell” is limited by the process of causing disruption in the processing of antigens and their presentation of it. There are multiple as well as sophisticated mechanisms are present which enable the M. Tuberculosis in the process of inhibiting as well as manipulating the pathways that are known for the purpose of presenting the T-cells.
- Mechanism of antimicrobial resistance
The mechanisms for antimicrobial resistance in processed through some steps, and these steps include:
Limiting the uptake of a specific drug
The core structure along with the active functions of the LPS layers in the context of gram-negative bacteria has provided a strong barrier in order to certain aspects of the molecule (Bernatchez& McCall, 2020). On the other hand, the useful aspect is highly responsive to provide innate resistance in terms of several groups of the agents which are listed as a large antimicrobial with a pathogen of tuberculosis. As per the view of (Allen et al. 2021), the layer of mitochondria is acted like an outer membrane which has a higher range of lipid content. As a result, it can be effective for hydrophobic drugs including fluoroquinolone and rifampicin which have easier access to cells.
Modification of the drug target
In the cell of the bacteria, there is the presence of multiple components that might act as the targets of the antimicrobial agents. Moreover, there are also as many a target in which modification is done by the activity of the bacteria which is responsible for enabling resistance to certain drugs. On the other hand, other processes of resistance building to the drugs that are in nature of type β-lactam are done by performing the alteration in the number of the structure of the Penicillin-binding proteins (Biadglegne et al. 2022). These PBPs are called the transpeptidases that are oriented with the process of constructing peptidoglycan that is present within the cell wall.
The changes being made in the number of PBPs impact the amount of drug that is going to be bound with the target. When the number of PBPs increases then the binding ability of the drugs becomes reduced, on the other hand, with the decrease in the number of PBPs the ability to bind the drug with the target gets increased (Endsley et al. 2021). Moreover, on the occurrence of a structural change taking place the binding ability of the drug is reduced or the binding of the drug is inhibited completely.
Inactivation of a drug
There are two different ways in which the drugs can be deactivated by M. Tuberculosis. One of the processes includes the degradation of the drug or the other process includes transferring a chemical group to the drug. One of the largest groups of Drug hydrolyzation enzymes includes the β-lactamases.
Active efflux of the drug
Some genres that are encoded at the chromosome level are possessed by the bacteria for the purpose of using them in the Efflux pumps. Some of these genes are expressed in a constitutive manner while the exposure of the others is done in either an induced manner or in an over-expressive manner and this is done under the presence of a certain type of stimuli or substance (Endsley et al. 2021). The primary function of the Efflux pumps is to aid the M. Tuberculosis cell in getting rid of the toxic materials. Moreover, these pumps are also responsible for supplying materials that aid the bacteria in resisting the action of the drugs. The capability of resistance reflected by these pumps is dependent on the availability of the type of source of Carbon.
Conclusion
The method of transmission of tuberculosis is by nuclei droplet from an infected person to a non-infected person however, the development of tuberculosis symptoms and disease varies due to differences in innate and active immune mechanisms present in the body. Different types of viruses show different types of characteristics and there are different types of infections caused by each of these bacteria. Moreover, the resistance techniques also depend on the types of bacteria. The study of the Virulence includes the pieces of information regarding a specific type of virus that aid in the prevention of the infections caused by the specific virus. Moreover, the knowledge gained through the virology study provides an idea of the impacts that can be caused by the virus. This article includes discussions on M. Tuberculosis. Various properties of the specific virus have been discussed along with the impacts of the virus, and the strategies through which it evades the human immune system and enters the body for causing infections.
Reference
Five primary References used in this report
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