Without the advancements of modern medicine, it’s pretty safe to say that a lot of us wouldn’t be alive right now. This is largely due to the revolutionary developments of antibiotics. Antibiotics have a dark side too, though. When they are over-prescribed, pathogenic bacteria can develop a resistance, meaning that they can defend against this medication and keep making people sick. There is, however, an unlikely candidate that could fill the shoes of antibiotics: anthrax.
When you mention the word “anthrax”, most people will probably think of some pretty scary things. Bacillus anthracis, the bacteria that causes anthrax, has long posed a threat to the lives of humans and livestock alike. It is a spore-forming pathogen that grows in the soil, and it can be transferred zoonotically, or from animals to humans. Currently, scientists think it originated in ancient Egypt or Mesopotamia, and scholars believe that anthrax was first documented as early as 700 BCE.
Figure 1. Bacillus anthracis under light microscopy. The bacteria itself is dyed purple, and the uncolored circles within it are its spores.
Inhaling the spores of B. anthracis can be fatal. Once dormant spores enter the body, they are activated by the abundance of water and nutrients in their new environment. From there, they are actively growing cells that multiply and spread throughout the body, producing toxins. Flu-like symptoms, chest discomfort, nausea, and even coughing up blood can happen anywhere from 1 to 42 days post-inhalation, and by the time symptoms are present, it might be too late to treat.
While B. anthracis was used in 1875 by Robert Koch to develop his famous Koch’s Postulates, it has more recently been used as a bioterrorist weapon. During the anthrax attacks of 2001, United States senators and other public figures were poisoned with anthrax, resulting in the death of five people with only a single gram of powdered spores. Because of this nation’s understandably fraught past with B. anthracis, mentions of it connote nation-wide panic. Despite this, however, one laboratory has discovered that using this bacteria could be largely beneficial in treating a myriad of different diseases.
Figure 2. The outer layers of B. anthracis.
As seen in Figure 2, one important structural feature of B. anthracis is its surface layer, or S-layer for short. This S-layer is made of a protein called Sap, and it can be found in lots of different kinds of bacteria; in the case of pathogens, it can serve as a virulence factor. This means that it can help the bacteria cause anthrax in the host through protecting itself against the immune system. The S-layer is only one component of a deeply complex cell surface that essentially functions as a suit of armor.
In one study of B. anthracis, Fioravanti et al. used types of single-domain antibodies and Nanobodies (Nbs), which are small pieces of antibodies, to control the assembly and structure of the Sap S-layer. These antibody fragments can break down Sap S-layers, which slows the growth of B. anthracis and alters its surface, altering that suit of armor. They found that when the Sap S-layer is present, the bacteria is easily able to evade a host body and cause anthrax disease. When the Sap S-layer is removed by Nbs, however, it is less effective in infecting the host.
Figure 3. B. anthracis SapAD tubules after being treated with single-domain antibodies.
In Figure 3, single-domain antibodies have been shown to be effective in inhibiting the growth of B. anthracis in a matter of minutes. Specifically, this pertains to SapAD, which is the Sap S-layer assembly domain. Its structures consist of sheets and tubules; the tubules are shown here, degrading in the presence of these antibodies.
Figure 4. B. anthracis after being treated with different sets of Nanobodies.
Not only does the use of Nbs disrupt the Sap S-layer assembly, but it also alters the structure and function of entire B. anthracis cells. When they were treated with different kinds of Nbs, the surfaces of B. anthracis cells changed drastically. Three different kinds of Nbs and a buffer, used as a control, were introduced to cultured B. anthracis cells. Cells in the control group developed normally, as did one of the Nb sets (NbAF703). Another Nb set (NbAF692) saw both normal cell growth (n) and scoured cells (s), which have an inconsistent, bumpy surface. In the most extreme case, the third Nb set (NbsSAI) was observed to present normal cells, scoured cells, and collapsed cell masses (c). NbAF692 and NbsSAI were both at least somewhat effective in altering the Sap S-layer of the bacteria, and therefore disarming them.
One of the most important discoveries of this study was found via experimentation on mice. In a later experiment, mice were infected with B. anthracis and were given Nbs as a treatment. Excitingly, the Nbs were just as effective in model organisms as they were in cell cultures. Specifically, NbsSAI was used, and mice that received ten injections over the course of their anthrax infection had a 100% chance of survival. Within a matter of days, the infected mice had recovered from anthrax, which would have been lethal without treatment.
The findings of this experiment have several implications in the medical world. First, it could revolutionize the way that doctors currently treat anthrax. Typically, anthrax is treated with antibiotics, but this can be dangerous in the long run; if antibiotics are used to treat diseases like anthrax too frequently, antibiotic-resistance strains of B. anthracis could easily come about. This would make the threat of another anthrax attack all the more intimidating. Because B. anthracis is discrete, easily-produced, and has a history of being effective, it could easily be used as a weapon in the future. If Nb treatment is found to be effective in humans, though, it could decrease the danger of B. anthracis poisoning, and eliminate the need for antibiotics to treat anthrax patients altogether.
Nbs could also eventually be used to treat other human diseases as well. For example, it is thought that Nbs could aid in the treatment of diseases caused by other bacteria with S-layers, such as Clostridium difficile, which causes colitis; Serratia marcescens, which causes ocular lens and urinary tract infections; and Rickettsia, which can cause Rocky Mountain spotted fever and epidemic typhus. The use of Nbs could drastically reduce the amount of antibiotics used in general, and it could also eventually serve as a more affordable alternative. If this method is as effective with these other bacteria as it is with B. anthracis, it is likely that it could be used to develop treatments for even more pathogens that have Sap S-layers. Ultimately, this could help combat the problem of over-prescribing antibiotics and ensure a treatment that is consistently effective, saving countless individuals from painful, deadly diseases like anthrax.
About the author:
Sophie Maxfield ’21 is a biology and art history double major from California. She works in the Woodard Lab at Mount Holyoke College studying the genetics of polyploid salamanders. Following graduation, Sophie plans to attend graduate school and eventually pursue a career in genetics research.
No comments:
Post a Comment