By Low Xun He Keefe
ABSTRACT
The rise of superbug cases in the last few decades and its impact on our immunology has been a hot topic of debate with many global researchers, scientists and healthcare professionals having varied outlooks on the vulnerability of humankind to such strains of bacteria. The concept of superbugs and the threat they pose to humankind is not a new concept with its first mention dating far back as the 1940s, with numerous scientists cautioning against the misuse of antibiotics which could result in such dangerous strains of bacteria. (1)
INTRODUCTION
To break down and gauge the effectiveness of the immune system’s defensive measures against superbugs, it is vital to establish the two entities at play here – the immune system and the strains of bacteria regarded as superbugs.
Our Immune system. A delicate and complex system that ties closely with the concept of emergence. The immune system is often mistaken simply for a group of specialised cells that protect the body. However, in reality, it is a much more sophisticated mechanism. It consists of hundreds of tiny organs, networks of vessels and tissues, billions of cells with dozens of specialisations and quintillions of free floating proteins. (2) As complex as it is powerful, the immune system is both a generalised and specialised weapon against all kinds of pathogens.
On the other hand, superbugs are strains of bacteria that have adapted and evolved due to the misuse of antibiotics. These bacterial strains evolve not only to develop complex resistance mechanisms that thwart the effects of many types of antibiotics, but have also evolved ways to pass on their resistance genes to other susceptible bacteria, increasing the pool of bacteria considered to be superbugs. Moreover, new research has also shown that these strains of bacteria have been able to adapt to the new burden of resistance with little to no cost to their fitness, making them more dangerous and difficult to overcome. (3)
Despite superbugs being highly adapted to deal with antibiotics, they are not as familiar with our immunology. Our immune system works differently from antibiotics, hence most people may believe that superbugs lack resistance against our body’s innate defences and do not pose a threat.
Unfortunately, this could not be further from the truth.
In order to develop this topic on the relations between our immunology and the effectiveness of its defenses against superbugs, firstly a rundown on the superbug existing and potential resistant capabilities against innate and adaptive immune defences, followed by what the lack of aid from antibiotics means for the effectivity of the immune system’s defences against superbugs, and lastly the risk factors that increases the chances of a superbug overcoming the body’s immune defences.
THREAT OF SUPERBUGS WITHOUT ANTIBIOTICS
Superbugs are resistant to most antibiotics which makes them extremely dangerous. However, in order to establish a link between the effectiveness of the immune system’s defences and superbugs, antibiotics will be removed from the picture and discussed on a later page. It is important to note that superbugs even without their adaptations are extremely dangerous strains of bacteria that can give the immune system a difficult time which is why antibiotics specialised for killing them were developed in the first place.
CAPABILITIES OF SUPERBUGS AGAINST THE INNATE IMMUNE DEFENCES
The innate immune system is one of two parts of the immune system. It is the part of the immune system that you are born with, containing generalised immune defences that target a broad range of pathogens.
INEFFECTIVENESS OF AMPs
The immune defences put up by the innate immune system consists partially of cytokines and other antimicrobial peptides (AMPs) that acts as one of the first few lines of defence. Examples of AMPs secreted by the body would be defensins, gramicidins, and cathelicidins that work as tissue protective mechanisms against the continuous adaptations of bacteria. However, this line of defence is often ineffective against many strains of superbug bacteria due to the bacteria’s ability to combat the antimicrobial activity of AMPs by physical avoidance through electrostatic repulsion. (4)
Beside being a line of defence, AMPs such as cytokines coordinate immune defences by acting as a medium of communication, directing immune cells travelling through the lymphatic system to the infection site. However, strains of persistent superbug bacteria are able to disrupt these cytokine communication networks, preventing the effective organisation of immune defences when an infection occurs.
One such cytokine network that requires mathematical attention would be the cytokine network that controls the TH1 and TH2 lymphocytes. Perturbation to this dynamic network could cause severe consequences for the organism’s ability to deal with infections. Research has shown that certain strains of strong, persistent bacteria such as Leishmania Major prevents organisms from inducing the correct TH1 cytokine network and thus being unable to activate parasitized monocytes to clear the infection. (5)
INEFFECTIVENESS OF SURFACE DEFENCES
The innate immune system also consists of surfaces such as the skin and mucous membranes that separates one’s insides from the external environment, ensuring that bacteria do not freely enter and colonize the body, infecting and damaging tissue. These surfaces that act as gantry points into the body prevent the infiltration of pathogens via the active removal of bacteria through physical processes such as the flushing of urine and the sweeping movements of cilia.
However, most of the immune defences protecting the skin and mucous membranes that rely on the active removal of bacteria are not as effective against many strains of superbug bacteria. This is because they have motility and attachment factors ( adhesins ) that allow them to stick to and colonise the surfaces that act as gantry points into the body, making infiltration easier. The immune defences of the skin and mucous membranes are further impaired by the toxins secreted by these bacteria, causing the partial or complete shutdown of these defence mechanisms. (6)
INEFFECTIVENESS OF RECOGNITION VIA RECEPTOR BINDING
In order to discern a pathogen from a civilian cell, immune cells use receptors to confirm the identity of a cell before taking action. One of the most common receptors used by immune cells to recognise a bacterial cell is the Toll- like Receptor 4. These receptors are therefore crucial to stopping an infection by providing “vision” capabilities to immune cells, allowing them to seek and destroy pathogens.
These receptors are extremely useful but ineffective against certain kinds of persistent superbugs. Many persistent superbugs hijack civilian cells, but instead of killing it, wears it as a cloak to prevent patrolling immune cells from binding to their receptors and being alerted to their presence.
These strains of bacteria also inhibit the release of chemical signals produced by the host civilian cell that would otherwise have been picked up by the receptors found on immune cells, alerting them to the invasion.
CAPABILITIES OF SUPERBUGS AGAINST THE ADAPTIVE IMMUNE DEFENCES
The adaptive immune system is the second part of the immune system that consists of specialised immune defences that specifically targets and kills the invading pathogen. The immune defences put out by the adaptive immune system are extremely difficult to overcome and incredibly effective against most pathogens including superbugs.
However, given the speed at which superbugs and other persistent strains of bacteria adapt to their surroundings, it is possible for them to evolve and phase out the threat of the adaptive immune defences under specific circumstances. It is extremely rare however, due to the burdens imposed on a bacterial cell’s fitness should they choose to evolve against the adaptive immune defences.
WHAT THE LACK OF ANTIBIOTICS MEANS FOR US
Many strains of superbug bacteria have evolved to the point in which no form of antibiotics engineered to target them is capable of killing them. This means that the option of antibiotic treatments has been ruled out, with the body having to rely on its own immune defences to fight. Superbugs, despite not having fully adapted to our immune defences, are still extremely dangerous and capable of causing death depending on the circumstances, which is the reason why antibiotics were formulated to specifically target and kill them in the first place.
Without being able to rely on antibiotic treatments as a cure, a variety of factors becomes crucial to whether the body is able to overcome the infection or dies from it. These factors mainly affect the strength of the immune system and the resources available to the invading pathogen.
RISK FACTORS
When it comes to the ability of the body’s immune defences to overcome superbugs, many risk factors are at play.
AGE
One of the most prominent factors at play is age. The strength of the adaptive immune system is highly dependent on the age of the individual, with adolescents having weaker, undeveloped adaptive immune systems that require time to mature. This is due to the difference between neonatal immune cells and adult immune cells. One such example would be T cells, whereby due to the lack of exposure to foreign antigens outside of the maternal alloantigens, they are not able to function as effectively and require major assistance from neonatal dendritic cells against any invading pathogen. (7)
Older people also have weaker adaptive immune systems due to the degeneration and degradation of immune cells. Most notably, there are changes in innate cell numbers with skewing of haematopoiesis towards the myeloid lineages. The senescent neutrophil also becomes less functional with decreased phagocytic ability and superoxide production. Simply put, the immune cells become unregulated and lose their capability to kill invading pathogens with the same proficiency as we grow older. (7)
INFECTION SITE
The location of the infection site is also an important factor when considering the ability of a superbug to overwhelm the body’s immune defences. Depending on the pathogen’s point of entry, there may be a varying amount of resources that it can use to grow and multiply. The extra resources may allow a pathogen to survive the heavy assault by the body’s immune defences and reach the bloodstream before being wiped out.
Moreover, if the infection site is close to the brain or other vital organs, it may be more or less accessible to the body’s immune system, making it more difficult to deal with and allowing the pathogen more time to spread and infect more tissue.
This is most notable if the infection is located within the meninges of the brain, where the lymphatic system is absent, and immune cells have to tread carefully to prevent widespread neurological damage, thus making the infection difficult to contain and deal with.
PRESENCE OF UNDERLYING CONDITIONS
Having underlying conditions can increase the mortality rate of an individual after contracting a disease caused by a superbug. Underlying conditions such as Human Immunodeficiency Virus (HIV) and Acquired Immunodeficiency Syndrome (AIDS) can directly affect the capability of the immune system making the body more vulnerable to all types of diseases. On the other hand, underlying conditions such as diabetes indirectly makes one more vulnerable to disease by slowing the healing of wounds in its victims allowing pathogens to enter breaches within the skin and infecting tissue.
LIFESTYLE
Susceptibility to disease caused by superbugs is also dependent on one’s lifestyle including a history of smoking, vaping, alcoholism and diet. For example, an individual with a prior smoking addiction would have severely damaged immune defence mechanisms meant to protect the mucosal surfaces within the lungs, therefore making the individual more vulnerable to superbugs that target the respiratory tract and lungs.
CONCLUSION
Many diseases caused by superbugs are extremely dangerous and given their immunity against engineered antibiotics, we can only rely on our bodies’ natural immunity to protect us. With that being said, many factors can affect the strength of our immune system which could directly affect one’s mortality rates should they contract a disease caused by a superbug. Since the factors are inexhaustible, it’s hard to determine just how efficient our natural immune defences are against these highly evolved strains of bacteria.
BIBLIOGRAPHY
1. Mark Honigsbaum (2018)
“Superbugs and us” volume 391, Issue 10119,
Retrieved from: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(18)30110-7/abstract
2. Philipp Dettmer (2021)
“Immune, a journey into the mysterious system that keeps you alive” Ch. 4, Pg 27
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“The superbugs: evolution, dissemination and fitness” Volume 1, Issue 5,
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“Bacteria Fighting Back: How Pathogens Target and Subvert the Host Innate Immune System” Volume 54, Issue 2 Retrieved from: 10.1016/j.molcel.2014.03.010
5.Michael Wilson, Robert Seymour, Brian Henderson (1998)
“ Bacterial Perturbation of Cytokine networks” PMCID: PMC108217
Retrieved from: 10.1128/iai.66.6.2401-2409.1998
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“Persistent Bacterial Infections: the interface of the pathogen and the host immune system”
Nat Rev Microbiol 2, 747-765 Retrieved from: https://doi.org/10.1038/nrmicro955
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“Evolution of the immune system in humans from infancy to old age”
Retrieved from: https://doi.org/10.1098/rspb.2014.3085
Edited by Romanea Kimhor
Astra Stem 
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