Commensual bacteria are a normal part of the human body and its tissues. Many commensual bacteria have components which can activate the immune system but they also express mechanisms to mute that activation. One interesting commensual that can cause serious disease is Neisseria meningitis. However this commensual is also found in many individuals as part of the normal flora and can use factor H and other strategies to "hide out."
Recently, it has been discovered that Neisseria meningitis can be activated to cause inflammation during host infection with influenza or other respiratory pathogens. It is activated via RNA thermosensors. RNA thermosensors are stretches of double stranded RNA that "melt" during high temperatures associated with fever. This melted RNA then can be used to make proteins etc...that may induce virulence. This is a fascinating response.
Since some microbiologists believe that normal flora bacteria were designed to be part of the human body, what role could these thermosensors play other than promoting virulence?
Do some research and find out more about how Neisseria meningitis hides out and evades the immune system and also come up with a theory that might explain its RNA thermosensor activation during viral infection.
DUE NOV10
It seems that from the handout that Dr. Francis gave us, that Neisseria miningitidis is able to hide from the immune system through these RNA thermosensors. When the temperature of the body rises due to fever, an RNA (which usually is in an inactivated hairpin form) changes conformation and is upregulated to produce capsule-synthesis enzymes that makes a capsule that protects it from the immune system. This thermosensor also regulates synthesis of factor H (regulates complement) and Lst (lipopolysaccharide molecules) to guard against the immune system. Without this, the Neisseria would be likely wiped out every time another pathogen induced fever. It is interesting to note that Neisseria only occurs naturally in the nasopharynx of humans and not really anywhere else. It is also interesting to note that the disease it causes is very well known and yet there is hardly anything written about the possible benefits to having it in your nasopharynx. As to how it could play in a role for good, I still got to think about it. There has to be something good about it being up there!
ReplyDeleteI found that an article on a virology blog that seems to explain the phenomenon quite well. It states that the translation is prevented by RNA secondary structure bound to the ribosome. This structure is stable at 30 degrees Celsius, but becomes denatured around 37-40 degrees Celsius. Since N. meningitidis lives in the upper respiratory tract, where it is cooler than body temperature (according to the article), it remains harmless in normal conditions. In the case of fever, this structure becomes denatured and allows the synthesis of proteins that evade the immune system. Some examples of these are proteins that bind complement, add sialic acid to the bacterial outer membrane,and produce a polysaccharide capsule. Inflammation caused by infection weakens the mucosal barrier allowing pathogens such as N. meningitidis to invade the blood and underlying tissues. Because it evades complement, the bacteria can survive in the blood. It is interesting that this bacteria is able to live without causing harm in an individual, until that person comes under attack by a virus (influenza) and then it takes advantage of the situation.
ReplyDeleteIt appears that upon acquisition of Neisseria meningitidis, the body does respond with antibodies, but it is within two-three weeks (slower response, as it is the first encounter). This may then eliminate the colony of N. meningitidis without further spread from the mucosal membranes (of the nasopharynx) to the blood stream or tissues. However, as N. meningitidis has the thermosensors, upon infection by another virus and induced fever (during the immune response), the raised body temperature “alerts” N. meningitidis that the body is fighting and thus “warns” it, that it may be in danger of being wiped out. Once the thermosensors are denatured, allowing the translation of proteins enhancing immune evasion (dealing with capsule synthesis, LPS or lipopolysaccharide modification, and complement-binding protein factor H). This defense mechanism also increases the virulence of N. meningitidis, but almost as a by-product of it attempting to escape elimination as a by-stander to the virus that brought about the infection/fever/heightened immune response in the first place. - T.A.
ReplyDeleteAlthough the thermosensors do indeed promote virulence, they may be present to merely aid N. meningitidis in evading elimination by the immune response when it is heightened due to infection by a different pathogen. If N. meningitidis is meant to reside in the mucosal membranes of the nasopharnyx region, it would be counter-productive to eliminate the population during any infection. That would be like wiping out your entire gut flora whenever fighting a pathogen. N. meningitidis is aerobic with oxidase and catalase activity. What that would do for the human carrier, I am not sure of. - T.A.
ReplyDeleteNeisseria meningitis is a bacterium that causes meningitis and can be deadly in children. This bacteria can hide out in the human body by entering host cells. N. Meningitis works in disrupting cell signaling and thus it is able to enter the host cells. The interesting and revolutionary concept of these bacteria is its thermosensors. When the host’s body begins to elevate its temperature due to fever, the bacteria is alerted by the raise in temperature and increases protein production in order to maintain survivability. These thermosensors are located on the RNA and will induce protein production involved with immunological resistance and increased virulence.
ReplyDeleteThese thermosensors could be activated as part of the RNA which is loosely folded. At a specific temperature, the RNA could then melt or unfold resulting in activation of translation of these proteins that defend itself against the host and promote virulence.
What still puzzles me, is that Neisseria meningitidis is only found in humans as far as we know and that in many people, especially in developing countries, it has no effect on its host until another bacteria activates it's thermosensors. There is a sense that when displaced from the nasopharynx, then it causes dreadful symptoms but as of now, it does not seem that Neisseria was displaced (such as v. cholerae and crustaceans) and that is what is causing it's virulence. Another thing is that of all places, it resides in the nasopharynx which is the pathway from the nose to the throat. Thus, it does not seem to keep out the competition of other bacteria (such as in the gut) and it does not seem to help the aid of digestion of other materials. So the question still remains, why is it up there? Is there any good that can come from N. meningitidis?
ReplyDeleteThe reason is the Neisseria meningitidis is found only in humans is because it needs transferrins and lactoferrin, it is only able to absorb iron sources from humans. The nasopharynx is probably the ideal environ for the bacteria to reside and thrive in.
DeleteThe main difficulty in determining the original purpose of Neisseria meningitis is that there is no knowledge of any benefits that N. meningitis provides. As Sean mentioned, it is very difficult to presume a role of something when we have no idea why it is there or any sense of the purpose that it plays. As far as I can tell, all we know is that it can live in the nasopharynx of humans, as it is only found there, and the only purpose we have found of it is simply evil. Perhaps such evolutionary thinking has played a part in the lack of knowledge of Neisseria meningitis’ role in humans. From a creationist perspective God created this world perfect and there was no evil or harm or pain. Contrasting, evolutionary thinking is based on survival through modifications and specification through death of the weaker and less competitive. According to evolutionary thinking, N. meningitis is simply a very competitive bacteria that has made it very far in our evolutionary history. From a creationist model this bacterium must have some fundamental purpose originally but evolutionist lack of seeing this view has limited their sight from looking for a good purpose. It appears to me that N. meningitis probably has some role in the nasopharynx and the thermosensors are there, designed in order to protect itself from being incorrectly killed due to a rise of temperature due to an immune system response. It is possible that the thermosensors have done microevolution to move from protection to doing evil in creating virulence. That would only be speculation though. All this to say, I don’t know why those bacteria are there or what they do but research should be directed that way and maybe we can learn more about this seemingly simply disastrous bacterium.
ReplyDeleteNeisseria meningitis (aka meningococcus) can be found to live in the throat of 5 to 10% of healthy people, attaching to non-ciliated columnar cells of posterior nasopharynx with its pili. It’s responsible for causing the epidemical disease meningococcal meningitis.
ReplyDeleteN. meningitis can usually live inside neutrophils cells, which make it possible for the bacteria to infect inflamed tissues.
These bacteria have an outer membrane toxin called lipooligosaccharide (LOS), which leads to deprivation chemokinetic and chemotactic factors in leukocytes. When temperature are above 37oC, it can mutate amino acid residues (by its RNA thermosensors) that can alter interactions with antibodies by mimicking the host cell surface, preventing the innate immune system from activating and allowing Neisseria to escape previous immune responses, hiding from it.
I really liked your response, Nathan. N. meningitis, as many other organisms that are harmful to other organisms, shows how the introduction of sin messed up with the whole perfect creation of God.
ReplyDeleteUnfortunately, death and illness are part of our lives and we need to learn how to face them, but what comforts us is that God is in control and that He let sin enters the world for His own glory.
Neisseria meningitidis is a bug that can be life- threatening, but lives peacefully in the nasopharynx region of many individuals. The problem occurs when the bacteria leaves the area behind the nose and enters the blood stream. This sort of bacterium is very interesting the way it evades the immune system. It misses the "first line of defence" by having phagocytosis activated. In a recent article published by PubMed.gov, states- Neisseria meningitidis remains an important cause of severe sepsis and meningitis worldwide. The bacterium is only found in human hosts, and so must continually coexist with the immune system. Consequently, N meningitidis uses multiple mechanisms to avoid being killed by antimicrobial proteins, phagocytes, and crucially, the complement system."
ReplyDeleteThemosensors present within bacterium like this, helps with virulence and with temperature regulations, unfolding RNA resulting with proteins that mimic the host.
-Peter F
It appears that the RNA thermosensors are activated by increased temperature (which occurs during inflammation) acts as a ‘danger signal’ for the meningococcus. This enhances its defence against human immune killing. Infection with viral pathogens, such as influenza, leads to inflammation in the nasopharynx with an increased temperature and recruitment of immune effectors. So it can be assumed that the thermosensors are turned-on initially through temperature chance and secondarily through inflammtion.
Deletehttp://www.nature.com/nature/journal/vaop/ncurrent/full/nature12616.html?WT.ec_id=NATURE-20130926
- jLo
Neisseria meningitides only evades the immune system and coexists with its human host 10 to 20% of the time. At this point it does not cause inflammation, but it does hide out using unique ways of evasion. One of these mechanisms is an IgA1 protease that cleaves IgA antibodies in the nasopharynx. It also attaches to neutrophils by its pilli. On the pilli of N. meningitides, there are CD46 receptors which are located on the neutrophil membranes. Though, the most prominent way of evasion is their RNA thermosensors which is located at the 5′ untranslated regions of genes. These genes are responsible for capsule biosynthesis, the expression of factor H binding protein, and sialylation of lipopolysaccharide (others ways of evasion). These genes express normally under the right conditions to hide out, but when another infection like influenza causes fever, the thermosensors are activated. The heat causes the RNA secondary structure to denature and promote faster protein synthesis by giving better access to the ribosome binding site. These immune evasion techniques become heightened and cause inflammation and disease.
ReplyDeleteOne of the problems in trying to understand this thermosensing mechanism in N. meningitides is trying to understand its benefits in the nasopharynx in the first place. Nothing has been found by researchers yet as to any benefits it would provide. Yet, it seems to coexist well with humans before it is agitated by the thermosensors. The thermosensors seem to just be a way for the N. meningitides to evade being destroyed. I’m not sure why it would then cause the N. Meningitides to become a pathogen in the body. Such a complex system to stay alive within the nasopharynx seems to be designed. Maybe there is a benefit to its convergence with neutrophils. It seems weird it would have receptors for CD46 if it was not for a purpose to work with a human host. I think more research needs to be done to understand the reason it hides out within a human host and what benefits it could have to understand the thermosensor mechanism more and its purpose.
ReplyDeleteH factor is a molecule that binds to the sugars on the cell surface. This prevents the immune system from destroying the H factor bound cell, by preventing any immune response against it. H factor is what keep our own immune system from destroying our own cells. Everything that is not marked by H factor is marked by compliments for destruction by the immune system. Neisseria Meningitis avoids being marked by the compliment system for destruction. Neisseria Meningitis is able to do this because it also has a protein on its surface that binds to the H factor. So this makes Neisseria Meningitis look like a human cell and so the immune system does not initiate an immune response against it.
ReplyDeletePriyank Puranik
The thermosensors not only regulates the virulence of the proteins, but it regulates two different states during the cold and heat shock response, it also helps to change their secondary structure which can change sections of RNA that is expressed and affects translation of coding genes.
ReplyDeleteAside from causing virulence, RNA thermosensors also plays another role in regulating the synthesis of metabolites such as sugars and amino acids. This mechanism is called riboswitches. Riboswitch RNAs control a broad range of genes in bacterial species, including those involved in metabolism or uptake of amino acids, cofactors, nucleotides, and metal ions. Regulation occurs as a consequence of direct binding of an effector molecule, or through sensing of a physical parameter such as temperature.
ReplyDeletehttp://genesdev.cshlp.org/content/22/24/3383.full
This is a way for the cell to self-regulate their genes expression through observing the temperature and therefore controlling the transcription and translation process.
- jLo
Neisseria meningitidis is a bacteria that is responsible for causing meningitis this is the inflammation of the meninges layer covering the brain. The N.meningitis lay mainly in the mucosal membranes particularly the digestive tract. The thermoreceptors seem to play an important role in preventing phagocytosis. This role of the thermoreceptors balances and allows certain bacteria to survive. The N.meningitidis shows importance of the host cell signaling pathways. When these are damaged and in this case inflamed by N. meningitidis there are serious problems.
ReplyDelete