C. difficile and the Microbiome: Read Article 06 M.
Rupnik, M.H. Wilcox, and D.N. Gerding, "Clostridium difficile
infection: new developments in epidemiology
and pathogenesis," Nature Revs Microbiol, 7: 526-536 (2009).
Post a
PCRC on the Blog. Ultimately, the class will be focusing how to describe
the mechanism of action of TCDA and TCDB, not the infection itself.
The Systems Biology of COVID-19 and the SARS-CoV-2 virus. The class will build a foundation that includes the emergence of complexity, simple biological subsystems, their reductionist and equivalent toy and organ-chip models, and the measurements required to specify model architecture and parameters. Applications to biology, physiology, medicine, chemical and biological defense, pharmacology, drug discovery, and toxicology. UGrad: PHYS 240 01 and BME 290B; Grad: PHYS 326 and BME 395C.
Cameron Togrye
ReplyDeleteAsgn_4C/C.Difficile and the Microbiome
0. Knew: Taking antibiotics can disrupt the natural balance of microorganisms that exist within the gut, and this can consequently leave one susceptible to infections.
1. Learned: Patients recovering from the hazardous strain of C. difficile have had the most success when they were given a faecal transplant. I had heard of these being used to restore normal microbiome composition, but didn't know they came into play with C. difficile.
2. Pressing: The article states that the two primary virulence factors of C. difficile, namely tcdB and tcdA, operate by disrupting the actin cytoskeleton and tight junctions of the epithelial cells in the intestinal tract. Does process expose the basal side of the epithelial lining to the lumen of the intestines? And if so, do C. difficile infections precipitate infection from other agents which take advantage of this weakening of intestinal epithelial cells?
3. Presentation: A discussion of bacterial spore formation
4. I thought it was particularly interesting that spore formation in virulent strains of C. difficile were found to be higher. I also was intrigued by the fact that exposure to sub-inhibitory concentrations of non-chlorine cleaners actually increased the sporulation capacity of the bacteria.
Kate Jones
ReplyDeleteArticle 6
0. Knew: Taking antibiotics over a long period of time can leave patients more susceptible to infection after stopping the antibiotics because antibiotic resistant bacteria that are normally kept under control by other bacteria have the opportunity to flourish.
1. Learned: I did not know the specific mechanism by which the infection causes damage to the intestine. I also did not know how extreme some of the effects of the infection can become!
2. Pressing ?: Is the purpose in learning about the particular infection and the toxins so that we can apply that knowledge of TCDB to the RTA challenge? If the bacteria infects the intestine, does the toxin have to travel through the bloodstream to affect the other organs mentioned such as the heart and lungs?
3. Presentation: I really liked figure 5 and the figure description because it helped me visualize how TcdA and TcdB get into the bloodstream and damage the intestinal lining. Having Figure 5 up on the projector when discussing the mechanism of action of tcdb and tcda could be very helpful.
4. It was interesting that the number of CDI cases has been increasing worldwide. Because the effect is so widespread, it seems like a change in hospital procedure resulting in more infection is unlikely. What type of other mechanisms could cause such a wide reaching increase in CDI?
Arman Chowdhury
ReplyDeleteAssignment 4C
0. Knew: Antibiotics can be dangerous too
1. Learned: CDI is a toxin mediated intestinal disease and its incidence is increasing. CDI occurs when the natural flora in the gut is disrupted by antibiotics. C difficile is resistant to wide range of antibiotics which enables the bacterium to colonize. Traditional gold standard for diagnosing CDI is a cytotoxin assay that detects the cell cytotoxicity of toxin B in fecal eluate. Vancomycin and metronidazole are prescribed for treatment, but no highly effective treatment has been found for severe complicated CDI.
2. Pressing ?: How far have researchers come close to understanding the bacterial interference mechanism during CDI in order to develop vaccines for the disease? Can CDI be contained by strict control of antibiotic prescriptions and hospital awareness?
3. Presentation: Summary boxes on “typing methods of C difficile” was useful to understand methods like PFGE (pulse field gel electrophoresis), MLVA (method of counting the numbers of repeat alleles in the genome that are amplified by PCR) and toxinotyping.
4. Thoughts: If agents like antibiotics are able to disrupt the microbiome-human coexistence and result in hard to treat infections like CDI, can we attempt to vaccinate ourselves against the most potentially harmful microorganisms in the microbiome as a preventive measure?
James Pino
ReplyDeleteAssignment 4C
0:Knew: Bacteria can become resistant to antibiotics
1:Learned: CD1 is a problem due to use of antibiotics. People in hospitals are more inclined to C. difficile difficulties. There is a need to find better detection and treatments .
3: Pressing: Is CD an example of application for RTA? Can CD be weaponized? Is the re-occurrence of CD the same as re-occurrence of cancer after treatment?
4:Thoughts: I didn't know anything about CD. I wonder if its possible to design something to absorb the toxins released, or if there are markers that one can target to prevent toxin release and also to induce apoptosis.
Nate Braman
ReplyDeleteAssignment 4C
0. Knew: The importance of gut flora. The dangers of antibiotic abuse.
1. Learned: CDI is a toxin-mediated intestinal disease most commonly found in elderly patients following antibiotic regiments. Some antibiotics cause disruption of gut flora, which allow C. difficile to proliferate and wreak havoc on the digestive tract. The most dramatic effects of CDI are caused by toxins TcdA and TcdB. TcdA disrupts tight junctions and loosens the epithelial barrier through cytoskeletal changes, and both toxins cause the release of immunomodulatory mediators. CDI is on the rise, and while it still predominantly occurs in elderly patients on antibiotic regiments, has been increasingly found in young patients or those without recent antibiotic consumption.
2. Pressing ?: If TcdB must pass through to the basolateral surface to bind, and rely on TcdA's disruption of epithelial cell tight junctions through bonding at the apical membrane, why is it that TcdA-TcdB+ strains remain virulent, whereas TcdA+TcdB- is not? Which strain will the RTA project be using, and why?
3. Presentation: Well organized, and an easy to digest (sorry..) introduction to a dense subject. Provided definitions and figures went a long way to clarify, though I think a flowchart based on the contents of Fig. 3 visualizing the interactions of the coding regions would have been a helpful addition.
4. Thoughts: There seems to be a strong need for a more reliable gold standard for CDI testing, with a more reasonable PPV. I feel that a two-step is probably a good idea - as the consequences of both a false positive and false negative are troublesome. I do not want CDI.
Mark Vander Roest
ReplyDeleteAssignment 4C
0. Knew: C. dif is a hospital associated bacteria that can cause some nasty infections in patients. It is resistant to certain antibiotics, making treatment difficult and infection likely when treated with those antibiotics. It produces specific toxins that are the agents of a negative host response.
1. Learned: The epidemiology of CDI, current techniques for identifying C dif and other bacteria (PCR ribotyping, PFGE, MLVA, REA), the concept of non-toxigenic CDI, specifics of antibiotics use and CDI,what the specific toxins C dif produces are and how they act (cytoskeletal changes and disruption of tight junctions, release of proinflamatory molecules).
2. Pressing ?: How would the new antibiotic published in Nature interact with C dif? Would it affect our gut microbiome in a more or less helpful way in terms of CDI?
3. Presentation: Overview of C dif infections, epidemiology, prevention, mechanism, etc.
4. Thoughts: Definitely a growing concern and I'm glad people are studying it heavily. I'm also really glad I'm not the nurse/doctor who has to do the diarrhea odor assessment.
Tim Lee
ReplyDeleteAsgn_4C/C.Difficile and the Microbiome
0. Knew: Strains that were antibiotic resistant caused issues. These strains are prevalent in the health care environment.
1. Learned: Patients who are hospitalized have a higher risk of contracting CDI. CDI occurs when natural gut flora are exposed to antibiotics. Methods of diagnosis include identifying diarrhea odor and cytotoxin assays. Main risk factor for patients is flora being disrupted by antibiotics, regardless of the antibiotic being present or not. Some of the mechanisms for how both toxins from CDI act.
2. Pressing: I'm confused to why a patient is at more risk when antibiotics are present to disrupt the flora. Is CDI usually an infection that occurs as a complication for trying to treat another bacterial disease? If it isn't, why aren't patients just not treated with the antibiotics to avoid the risk of CDI altogether?
3. Presentation: CDI and its growing prevalence. Risks, prevention, mechanisms, etc.
4. Thoughts: It was cool to learn more about a type of infection that actually has more risk of being contracted by being in a hospital setting. Also scary to think there are infections that tend to thrive in the presence of antibiotics.
Chuck Herring
ReplyDeleteAssignment 4C
0. Knew: General information about the microbiota and its role in human health.
1. Learned: How antibiotics can compromise the environmental health of the microbiota and can lead to an increased risk CDI infection.
2. Pressing: Through what mechanisms does a healthy microbiota prevent CDI infection?
3. Presentation: A nice review about all aspects of CDI infections?
4. Thoughts: To what level, does the microbiota and the host interact chemically/ mechanically?
Cami Johnson
ReplyDeleteAssignment 4C: Article 6
0. Knew: Antibiotics can disrupt natural "good" bacteria in the body, allowing for infection of "bad" bacteria.
1. Learned: C. difficile infection is a common hospital-associated infection resulting from the disruption of the typical bacterial population in the gut by antibiotics. The two main virulence factors of C. difficile are toxin A and B (TcdA and TcdB). These toxins result in the primary symptoms of CDI: diarrhea and inflammation of the colonic mucosa.
2. Pressing ?: If TcdA+/TcdB- mutants are not virulent, what role does TcdA play in CDI infection? Can TcdB travel through the bloodstream and cause problems via an inflammatory response in another part of the body?
3. Presentation: An overview of the infection caused by C. difficule, including the cause, diagnosis, mechanism, prevention, and treatment.
4. Thoughts: With antibiotics, it always seems like there's such a balance between the good they do and the problems they can cause. Hopefully, there could be better antibiotics discovered which won't result in such a disruption of the body's natural microbiome.
Shuaipeng "Jimmy" Zhang
ReplyDeleteAssignment 4C
0. Knew: Bacteria can develop resistance to antibodies. Antibodies can affect the natural microbiome in a negative way.
1. Learned: Treatment of CDI with vancomycin. Risk factors for C. difficile, and current detection methods. Toxins produced by C. difficile, and the production of spores by the bacteria.
2. Pressing ?: The article states that C. difficile can only colonize the gut if the normal intestinal microbiota is disturbed or absent. Have researchers identified the strains of normal intestinal bacteria that must be affected in order for C. difficile to persist?
3. Presentation: Causes, prevention, current treatment and diagnostic techniques of CDI.
4. Thoughts: I was not familiar with CDI before reading this article, and the prevalence of this disease was quite shocking, about 500,000 cases of CDI per year in U.S. hospitals. About what percentage of people are immune to this disease?
Priyanka Ravichandran
ReplyDeleteAssignment 4C - Article 6
0. Knew - Taking antibiotics can actually leave an individual more susceptible to infection
1. Learned - what is CDI infection and its effects; the extent of the CDI problem worldwide
2. Pressing - how can we use our knowledge of microbiota to develop a more effective treatment for CDI?
3. Presentation - provides information on our current knowledge of C. difficile infection
4. Thoughts - I didn't know CDI was such a serious problem. I know antibiotics can be both helpful and harmful but maybe by looking into how microbiota play a role in this disease and analyzing the microbiota of people who overcame or are immune to this disease, a more effective treatment can be developed.
Selene van der Walt
ReplyDeleteAssignment 4C
0. Knew: about the general prevalence of C. difficile infections, but not about the changing epidemiological factors and their effect on the clinical response.
1. Learned: about the increase in CDI in Europe and North America since 2002. Also learned more about the relationship between hospitalization and antibiotic use and contraction of CDI, as well as the typing methods for CD (PCR ribotyping, PFGE, MLVA and REA). Also how long after antibiotic treatment stops the normal gut flora can continue to be disturbed.
2. Pressing ?: What are the most effective ways to safeguard patients in hospitals from contracting CDI? How can these be implemented on a wider basis?
3. Presentation: The nature and changes in CDI in the past decade, with specific regard to the impact on antibiotics on the normal gut flora.
4. Thoughts: It was very interesting to learn more detail about CDI, I did not realize the extent to which antibiotics can influence normal gut flora, nor how easy it is to catch a CDI from the hostpital environment. I'm still not entirely sure what has caused such a widespread increase in CDI over the past years.