The human body has always been special to scientists because it has this amazing capacity to repair itself (like a broken bone) and to protect itself from any kind of exterior aggressions. After studies and a lot of research, it was discovered that peptides in the body are one of the reasons why it can face pathogens and stay healthy.
One kind of peptide is very important in the body, which is the antimicrobial peptide (AMP). These peptides are essential to the body's natural defense against diseases. They ward off invading microbial pathogens such as viruses and bacteria. Also, they have had a major role in the development of therapeutic agents to prevent and treat diseases, which has become even more important, considering the situation we are facing now.
But like any other human cell, it also has the capacity to evolve over time. And sometimes, AMPs are not enough to face threats that have also evolved and found a way to resist. In consequence, it leads to some inconveniences like skin problems, respiratory infections, among other issues.
So how can these antimicrobial peptides help fight these aggressions? And what are the latest developments made concerning this subject?
AMPs: the ancient weapon of the human defense system
Antimicrobial peptides (AMPs) form an ancient type of innate immunity and are considered as the original mechanism of the human body’s defense. With studies and research on insects, plants and humans, it is now proven that they deploy their AMPs as an antibiotic against microbes. They are also crucial to human survival.
The ability of AMPs to kill bacteria depends upon their efficiency to interact with bacterial membranes or cell walls. Normally, AMPs show a positive charge and a high ratio of hydrophobic amino acids, which bind negatively charged bacterial membranes. This entire process is what stops infections from appearing.
With time, these peptides have evolved but they have not lost the ability to kill or prevent the microbes in their entirety. Therefore, they have the potential to contribute to a major breakthrough, and form the basis of new antibiotics. Scientists and biochemists have brought attention to the remarkable functions and structure of these AMPs, in terms of understanding human biology and the immune system. It has now become a tool to create new anti-infective drugs.
Unfortunately, the microbes have also found a way to evolve in time, which allows them to face the AMPs and create bacteria that resist antibiotics.
Antimicrobial peptides for human skin diseases
The skin always encounters microbial pathogens. To protect against them, the epidermis and dermis cells created several solutions to avoid infections. AMPs are one of the first mechanisms used by the skin. Usually, these peptides are very efficient towards bacteria.
However, AMPs are not just defenders, they are also host cells to stimulate cytokine production, cell migration, proliferation and maturation. So, when the skin produces AMPs, they also increase after infection, inflammation or injury. However, some skin diseases can show other expressions of AMPs. The research made on this subject revealed that understanding how peptides defeat microbes, skin inflammation, and heal wounds, offers more insights into the pathophysiology of skin disorders, and facilitates finding new treatments for these diseases.
With time and research, it has been discovered that chronic intestinal inflammation was linked to damaged antimicrobial peptides, and it is possibly provoked by an altered expression and secretion of AMPs, like in Crohn’s disease, for example.
Also, an abnormal expression of AMPs have been linked to atopic dermatitis, which is a chronic relapsing inflammatory skin disease. On the contrary, an overproduction of AMPs can provoke inflammatory diseases. For example, people with psoriasis, which is a chronic auto-inflammatory skin disease, have an excess of AMPs in the body. For those with rosacea, it is caused by an elevated expression of cutaneous proteinases. Research on AMPs and skin disease availed multiple opportunities to find treatments.
As all living creatures will always be threatened by lots of microorganisms wanting to use the same environment space, new ways to face these microbial threats by killing or inhibiting their growth are being researched.
Antimicrobial peptides to treat respiratory infections
Antimicrobial peptides are little molecules in all living organisms, and they serve as immunity defense. For some animals, they have the major role in respiratory airways. A respiratory infection can be caused by bacteria, viruses, and parasites, since the airways are always exposed to microbial pathogens, the environment, particles etc.
At first, when an infection arises in the airway or in the lungs, it is combatted by these peptides. But sometimes the antimicrobial peptides are not enough to beat the infection. With time, some diseases evolve, and they become more difficult to beat. In some cases, antibiotics are not enough.
The resistance to antibiotics has become a serious problem in a lot of countries, especially during the Covid-19 pandemic we are currently experiencing. In this case, the respiratory infection has a very high epidemic potential and high transmission rate caused by antibiotic-resistant bacteria. The development of new antimicrobial agents against these diseases are required now, more than ever.
So far, several antimicrobial peptides have been evaluated, and they have yielded promising results. They act on the respiratory chain and resist diseases. These peptides have a direct killing action, and they also show high immunomodulation activity. With all the progress made in research and development, it is now considered that antimicrobial peptides are the antibiotics of the future. Its incidence in respiratory and pulmonary diseases is very pertinent, and the utilization of these peptides from human and animal sources could come to be part of a medical practice in the future.
Antimicrobial peptides and the latest advances in their development
The recent increase of antimicrobial resistance has been admitted by major organizations such as the United Nations and the World Health Organization, as well as large countries like the United States and major European countries.
These AMPs are recognized as the new weapon to eradicate severe infections, caused by drug-resistant bacteria, and are under intense scrutiny as they are to become the future of antibiotics. They are currently being developed to kill severe bacterial infections, and overcome drug resistant bacteria.
While many of these peptides are natural, more and more are produced in laboratories, and are chemically synthesized to achieve new agents. This system is also favored to preserve human and animal health.
Challenges for therapies with AMPs
Creating new therapies with AMPs is the solution to defeat a lot of diseases, but due to their peptide nature, it can be quite problematic at times. For example, peptide drugs need to be injected or inserted directly into the affected tissue. And unfortunately, AMPs are no exception.
Two major issues decrease the efficiency of these peptides: they survive only a few hours, and they have trouble penetrating the tissues. It they are taken as pills, they are broken before they arrive in the bloodstream, which makes them useless. This makes it difficult to achieve enough peptides for longer periods of time, and several injections per day are currently necessary.
Usually, the bacteria has more problems to resist AMPs due to two reasons. First, AMPs kill bacteria very quickly and they can have multiple targets in the bacteria, to maximize their chances of killing them.
Over the years, researchers have been challenging the AMP’s resistance via new experiments. In 2017, and in the same condition as in the human body, scientists and researchers cultured bacteria and exposed them to four AMPs (from different sources like plants and animals) for seven days. AMPs were able to kill a portion of the bacteria, but after some time, other types of bacteria emerged. After more analysis, the bacteria showed lots of changes, mostly genetic, which made them more resistant to the other AMPs, and to the antibiotics.
The positive outcome is that these changes were stable, which means the resistance was maintained in the absence of AMPs. Moreover, these changes didn’t alter the bacteria growth or its ability to provoke diseases.
Right now, it is important to know whether this resistance is inevitable. Of course, when it is in a laboratory, the experiment can be criticized for its setup (the selected AMPs, as well as the use of these peptides). When it is made this way, the setup is more optimized to select resistant peptides, and reflect the real conditions of infection less. Nonetheless, these experimentations emphasize the in-between process. In real conditions, the resistance development isn’t as fast, but is as persevering. Although, scientists proved that if AMPs are used like antibiotics (for everything and in a bad way), resistance is sure to be inevitable.
It is important to know that if one peptide causes resistance, it can lead to resistance from the others, which will provoke a “cross-resistance”. If the resistance to AMPs keep increasing, it will contribute to weaken the human immune system, which could have enormous consequences for every person who contracts these bacteria.
