Essay On Yersinia Pestis
Extra Credit Assignment
This paper will be based on three articles that were assigned: Lipopolysaccharide modification in Gram-negative bacteria during chronic infection, Fortifying the barrier: the impact of lipid A remodelling on bacterial pathogenesis, and Pathogenicity of Yersinia pestis synthesis of 1-dephosphorylated lipid A. It will be a summary and my opinion of each article.
The first article has to do with Gram-negative bacteria lipopolysaccharide layer(LPS) and how it plays a key role in host-pathogen interactions in the immune system. Specifically having to deal with chronic infections and how a modified LPS layer has different effects on it. In chronic infections these modified LPS layers have a tendency to cause host immune systems to be evasive and cause constant inflammation.
The most common pathogen isolated from the airway of Cystic Fibrosis patients is Pseudomonas aeruginosa. Phenotypic changes in the bacteria have shown that some have undergone a mutation …show more content…
that aids in the pathogenesis. P. aeruginosa has been found in over 80% of patients with CF and the majority seem to be mutated. These mutations include, loss of motility, reduced expression of virulence factors which causes the host immune system to overlook them, and increased activity of efflux pumps that are associated with antibiotic resistance. The extensive diversity of this bacteria in chronic infections causes it to make population centers that allow for LPS layer mutations which affect antibacterial resistance. This is a main reason why chronic infections are difficult to combat. This mutated strains appear to have very few to zero O side chains which make it non-typeable.
The first study also looked at LPS variation for chronic gastric infections. Helicobacter pylori is a major bacteria involved in gastric chronic infects and a main reason is due to a missing repair gene which causes it to mutate very frequently. Structural modifications of the lipid A layer cause it to mutate and mimic host components. Like P. aeruginosa this causes it to go undetected by the host immune system.
Concluding this article it seems as though LPS-mediated endotoxic activity comes down to lipid A activity and the O-antigen. Both of these cause a disguise in the host immune response and increase the pathogenesis of the bacteria. This cause them to be long term chronic infections.
The next article has to do with the remodeling on the lipid A layer and how that affects pathogenesis. For most lipid A modifications a enzyme is embedded nearby the lipid A on the outer membrane. You also have transcriptional and post-translational regulation of lipid A. Both of these can be modified to improve pathogenesis. This article also talks about how rare the colonization of pathogenic bacteria actual is in relation to the amount of bacteria that we encounter daily. This is in large part due to our great immune system, but these modifications to the lipid A can compromise our ability to recognize pathogenic bacteria.
Host immune response can also be avoided by bacteria via chemical groups. Another way to accomplish this is by changing the structure of lipid A. This will affect recognition by the TLR4-MD2 receptors. Both of these lessen the assault that is brought on by the immune system and allows them to survive in the body.
Recent studies have even shown that lipid A modification is directly correlated and crucial to bacterial pathogenesis. So understanding lipid A seems more and more important to us as we study gram-negative bacteria. There even may be a correlation on how certain viruses attach to LPS layer and specifically lipid A but we are waiting for more research to be conducted in that area. Using mice has been semi successful but it is very difficult to replicate a human immune response in a mouse. Along with a better understanding of how the body responds to lipid A changes, the article talks about how certain treatments can be applied to individuals who have certain pathogens in their body.
The last article goes over Yersinia pestis and its synthesis of lipid A and how that affects pathogenesis.
They lay forth an experiment to test a hypothesis. Like the previous two articles this discusses how altering the LPS layer and specifically the lipid A can mask the bacteria from the host immune response. The article showed that certain phosphate groups, specifically C-1 and C-4 lead to more endotoxicity and septic shock in hosts. Removal of one of these phosphate groups has shown to greatly reduce lipid A toxicity. Now the removal of this phosphate group was the hard part and did not always work, but they inserted F. tularensis lpxE into the LacI site of Y. pestis chromosome. In the end it did appear to work under certain circumstances and the mice showed an immune response and became inflamed before becoming very ill. Although becoming very ill is not ideal, it did show an immune response which therefore altered the lipid A enough for the mice immune system to recognize
it.
All of these articles had a similar theme in that by looking at gram-negative bacteria and seeing that the LPS layer and more specifically the lipid A can cause the pathogenic bacteria to become unrecognized. The research articles presented all showed ways of altering these targets so that they could be recognized. Most were successful in this but some had only been tested on mice and that is difficult to translate to success in a human host as the immune responses are different. There are attempts to insert more host components into mice for testing but this is still developing. All of these studies did however show a promising outlook on the future for treatment of pathogenic bacteria. Especially with regards to alternatives from antibiotics which have proven to show lots of good but also creating more dangerous strains. All in all these were very useful articles to point to where the future is headed and how further research can lead us to improving treatment.
This paper will be based on three articles that were assigned: Lipopolysaccharide modification in Gram-negative bacteria during chronic infection, Fortifying the barrier: the impact of lipid A remodelling on bacterial pathogenesis, and Pathogenicity of Yersinia pestis synthesis of 1-dephosphorylated lipid A. It will be a summary and my opinion of each article.
The first article has to do with Gram-negative bacteria lipopolysaccharide layer(LPS) and how it plays a key role in host-pathogen interactions in the immune system. Specifically having to deal with chronic infections and how a modified LPS layer has different effects on it. In chronic infections these modified LPS layers have a tendency to cause host immune systems to be evasive and cause constant inflammation.
The most common pathogen isolated from the airway of Cystic Fibrosis patients is Pseudomonas aeruginosa. Phenotypic changes in the bacteria have shown that some have undergone a mutation …show more content…
that aids in the pathogenesis. P. aeruginosa has been found in over 80% of patients with CF and the majority seem to be mutated. These mutations include, loss of motility, reduced expression of virulence factors which causes the host immune system to overlook them, and increased activity of efflux pumps that are associated with antibiotic resistance. The extensive diversity of this bacteria in chronic infections causes it to make population centers that allow for LPS layer mutations which affect antibacterial resistance. This is a main reason why chronic infections are difficult to combat. This mutated strains appear to have very few to zero O side chains which make it non-typeable.
The first study also looked at LPS variation for chronic gastric infections. Helicobacter pylori is a major bacteria involved in gastric chronic infects and a main reason is due to a missing repair gene which causes it to mutate very frequently. Structural modifications of the lipid A layer cause it to mutate and mimic host components. Like P. aeruginosa this causes it to go undetected by the host immune system.
Concluding this article it seems as though LPS-mediated endotoxic activity comes down to lipid A activity and the O-antigen. Both of these cause a disguise in the host immune response and increase the pathogenesis of the bacteria. This cause them to be long term chronic infections.
The next article has to do with the remodeling on the lipid A layer and how that affects pathogenesis. For most lipid A modifications a enzyme is embedded nearby the lipid A on the outer membrane. You also have transcriptional and post-translational regulation of lipid A. Both of these can be modified to improve pathogenesis. This article also talks about how rare the colonization of pathogenic bacteria actual is in relation to the amount of bacteria that we encounter daily. This is in large part due to our great immune system, but these modifications to the lipid A can compromise our ability to recognize pathogenic bacteria.
Host immune response can also be avoided by bacteria via chemical groups. Another way to accomplish this is by changing the structure of lipid A. This will affect recognition by the TLR4-MD2 receptors. Both of these lessen the assault that is brought on by the immune system and allows them to survive in the body.
Recent studies have even shown that lipid A modification is directly correlated and crucial to bacterial pathogenesis. So understanding lipid A seems more and more important to us as we study gram-negative bacteria. There even may be a correlation on how certain viruses attach to LPS layer and specifically lipid A but we are waiting for more research to be conducted in that area. Using mice has been semi successful but it is very difficult to replicate a human immune response in a mouse. Along with a better understanding of how the body responds to lipid A changes, the article talks about how certain treatments can be applied to individuals who have certain pathogens in their body.
The last article goes over Yersinia pestis and its synthesis of lipid A and how that affects pathogenesis.
They lay forth an experiment to test a hypothesis. Like the previous two articles this discusses how altering the LPS layer and specifically the lipid A can mask the bacteria from the host immune response. The article showed that certain phosphate groups, specifically C-1 and C-4 lead to more endotoxicity and septic shock in hosts. Removal of one of these phosphate groups has shown to greatly reduce lipid A toxicity. Now the removal of this phosphate group was the hard part and did not always work, but they inserted F. tularensis lpxE into the LacI site of Y. pestis chromosome. In the end it did appear to work under certain circumstances and the mice showed an immune response and became inflamed before becoming very ill. Although becoming very ill is not ideal, it did show an immune response which therefore altered the lipid A enough for the mice immune system to recognize
it.
All of these articles had a similar theme in that by looking at gram-negative bacteria and seeing that the LPS layer and more specifically the lipid A can cause the pathogenic bacteria to become unrecognized. The research articles presented all showed ways of altering these targets so that they could be recognized. Most were successful in this but some had only been tested on mice and that is difficult to translate to success in a human host as the immune responses are different. There are attempts to insert more host components into mice for testing but this is still developing. All of these studies did however show a promising outlook on the future for treatment of pathogenic bacteria. Especially with regards to alternatives from antibiotics which have proven to show lots of good but also creating more dangerous strains. All in all these were very useful articles to point to where the future is headed and how further research can lead us to improving treatment.