User:Mcgue.13

My Topic for this Research Project is: How has the evolution of immune defense and antibiotic resistance changed how we combat illnesses?

Annotated Bibliography:

Joshua Lederberg. Infectious History (14 April 2000); Science 288 (5464), 287. This paper outlines the trans-global history of the disturbing coevolution of humanity and microbes.According do the author, ultimate survival may entail humans implementation of a more microbial standpoint.

Julian Davies, Dorothy Davies. Origins and Evolution of Antibiotic Resistance; Microbiol Mol Biol Rev. Sep 2010; 74(3): 417–433. These two authors draws out concerns for the use of antibiotics with the rising antibiotic resistance in medical settings, communities, and the environment. The paper shows how astonishing genetic abilities of microbes have defeated the push of antibiotics since the 20th century. The authors also talk about the significant aspects of antibiotic resistant developments, which have been occurring more frequently then ever.

Adam J. Dobson, Joanne Purve, Jens Rolff. Increased survival of experimentally evolved antimicrobial peptide-resistant Staphylococcus aureus in an animal host. (2 July 2014) Evolutionary Applications. This paper outlines information regarding Antimicrobial peptides (AMPs) and how they have been introduced as a new type of antimicrobial drug due to the rising resistance to antibiotics. The authors discuss how synthetic AMPs are practical analogs of highly evolutionarily preserved immune effectors in animals and plants.

Saver R. In Tepid Defense of Population Health: Physicians and Antibiotic Resistance. American Journal Of Law & Medicine [serial online]. December 2008; 34(4):431-491. Available from: Health Source: Nursing/Academic Edition, Ipswich, MA. Accessed September 15, 2014 This journal describes how antibiotic resistance is disturbing our population and how it is a threat to public health overall. A lot of studies have been focusing on how the supply side of antibiotics is effecting the resistive capabilities of certain microbes. Physicians now a days have a huge role in helping combat the growing resistance to antibiotics, and must manage that supply of antibiotics to prevent further recessive strains of microbes.

Ubeda C, Pamer E. Antibiotics, microbiota, and immune defense. Trends In Immunology [serial online]. September 2012;33(9):459-466. Available from: Academic Search Premier, Ipswich, MA. Accessed September 15, 2014. This journal describes the gastrointestinal tract micriobiota and how they contribute to the evolution of our immune system. The authors describe how the composition of these mircrobiota systems and their importance in our immune system. Then, the authors also discusses antibiotic administration and what is being done to combat the growing resistance to some of the medicine. Lastly, the paper discusses how antibiotic induced disturbances of the microbiota and immune homeostasis can lead to disease formation.

-- Due Oct 1. 3 Suggestions and one sentence with a citation.

Link to article used: https://en.wikipedia.org/wiki/Antibiotics

Administration
Since you are listing multiple different types of antibiotics in this section, you should describe each one, and what it does. Or else you are pretty much wasting space because I and anyone not too familiar with specific types of antibiotics would have no clue what each of them are/do. — Preceding unsigned comment added by Mcgue.13 (talk • contribs) 01:13, 1 October 2014 (UTC)

Pharmacodynamics
This article primarily focuses on antibiotics, however this section is entirely about antibacterial and antimicrobial topics. These are similar topics, but are not necessarily relevant to the entire article. A reader seeking to gain information on antibiotics probably will read this section and not look back on it sense there is no relevant information. My opinion would be to remove this section from the article, and perhaps insert it into another article regarding antibacterial and antimicrobial topics. — Preceding unsigned comment added by Mcgue.13 (talk • contribs) 01:13, 1 October 2014 (UTC)

Production
Reading over the production section of this paper interests me in learning more and make me wish that there was at least a little bit more about how antibiotics are created whether it be fermentation is explained in a simple way, or a recent new chemical pathway. There is a lot of research being conducted as we speak regarding the production of antibiotics and it would be helpful to include some of these processes here. — Preceding unsigned comment added by Mcgue.13 (talk • contribs) 01:13, 1 October 2014 (UTC)

Sentence and citation

 * Nonoperative resource for patients who have non-complicated acute appendicitis. Treatment with antibiotics has proven to work, with almost no cases of remission.
 * Kırkıl C. Long-term results of nonoperative treatment for uncomplicated acute appendicitis. The Turkish journal of gastroenterology. 2014-08;25:393-397.

FINAL DRAFT
Evolution of Antibiotics Resistant Pathogens Driving the Need for Alternative Antimicrobial Therapy Methods - For a very substantial period of time, infections have claimed the lives of many people. Throughout the 19th century, tuberculosis, pneumonia and diarrhea were credited with taking the lives of children and adults and in fact were one of the leading causes of death during that period (Zaffiri 2012). Correlating the deaths with these diseases was a huge success; it became clear that there was a common source: pathogens (Zaffiri 2012). Overall public health has continuously improved since the discovery of pathogens (Lederberg 2000). The discovery of pathogens and how they are spread have resulted with health care providers and other government agencies adapting new precautionary measures to limit the spread of pathogenic bacteria (Lederberg 2000). Infections are still prevalent today, but since the introduction of antibiotics in 1911, there has been a decreased amount of deaths due to bacterial infections (Lederberg 2000). Arsphenamine, the first antibiotic, was introduced by Paul Ehrlich and generated a snowball effect on how physicians treated infections (Zaffiri 2012). With the vast knowledge that researchers and physicians have on how to treat these diseases, it is logical to think that the prevalence of these pathogens would diminish. However, recent studies prove that this is not the case due to the quick evolving nature of some of these pathogens. Antibiotics are one of the world’s greatest inventions, however they may be aiding in the rising populations of super-resistant pathogenic bacteria (Davies 2010). Microbes have been benefiting by the misuse of antibiotics and have been digging deep into their gene pool to come up with resistant genes to antibiotics. Then the microbes pass on those resistant genes, making an entire new population of resistant bacteria (Davies 2010). This creates a major problem in the health industry creating a new fear of entering the “preantibiotic” era once again (Sulakvelidze et al., 2001). A huge area of research is being conducted in search of new ways that we can combat these microbes, which have become resistant to current treatments. Evolution is a process that has been studied for a very long period of time and by understanding how certain microbes evolve will certainly aid in defense strategies. Regrettably, one thing learned thus far is that the quick rise of antibiotic resistance may be due to human error when prescribing or taking antibiotics (Davies 2010). Through uncontrolled and the over-usage of antibiotics, they have quickly become irrelevant to some of the microbes. Until researchers understood this, many different strains of bacteria became resistant to many drugs, which was especially heavily prevalent in hospitals. The year of 1937 marks the first effective antimicrobials, which were the sulfonamides (Davies 2010). However with these successful antimicrobials, resistance of microbes were beginning to be reported (Davies 2010). The way that these populations become resistant to antimicrobials, antibiotics, is noted through rapid reproduction and large genetic variation throughout the population (Davies 2010). These microbes have exploited beneficial genetic mutations that are able to be passed on, and in fact have characteristics that allow them to combat the antibiotic. A specific way that a microbe, particularly the ones that sulfonamides target, might combat antibiotics is by effluxion (Davies 2010). Effluxion is when a particular substance is being excreted or thrown out. Pathogens may efflux by getting rid of the toxins that antibiotics are trying to disperse to fight the infection (Davies 2010). Another common way that microbes combat antibiotics is by changing their main target. They may have a gene that will allow them to go after a different bonding site, allowing them to continue to reproduce and pass on that trait while at the same time, staying away and not being affected by the antibiotic (Davies 2010). These are just two examples that are extremely common in antibiotic resistant microbes, however there are many more tactics that microbes use in order to survive medical drugs. A recent discovery also displays how some microbes have used multiple techniques for evading the effects of antibiotics resulting in microbes that are resistant to more the one antibiotic (Davies 2010). These microbes are referred to as superbugs. Superbugs are classified as being heavily resistant to many different antibiotics, which can be a huge problem when doctors are caring for a patient (Davies 2010). The name superbugs was derived from microbes that have increased morbidity due to excessive amounts of mutations which help them survive treatments of multiple types of antibiotics (Davies 2010). After accumulating these multiple beneficial mutations, the next generation of microbes will continue the resistance pattern, which leaves researchers with the project of developing new drugs or new treatments to try to combat the microbes. One of the most well known superbugs is the HIV, which ultimately results in AIDS (Lederberg 2000). Research has been conducted throughout many years, yet AIDS and HIV still are able to resist treatments (Lederberg 2000). This relationship of superbugs to antibiotics as well as other treatment methods is similar to that of a co-evolutionary arms race in which microbes are fighting to be resistant and as they become resistant researchers are trying to find new ways to defeat them. Antimicrobial peptides (AMPs) are one of the new methods in which health care providers are beginning to treat patients who are infected with antibiotic-resistant pathogens (Dobson et al. 2014). AMP therapy was developed in light of the increasing populations of resistant bacteria and is used as an antimicrobial drug (Dobson et al. 2014). AMPs are widely seen in multicellular organisms naturally as they are very important when it comes to immune defense (Dobson et al. 2014). They were also noted as being a “resistant proof” treatment option for bacterial infections until later discoveries proved otherwise (Dobson et al. 2014). Some populations of pathogenic bacteria have developed beneficial mutations, which have allowed them to become resistant to AMPs just as they became resistant to antibiotics. However, there are only a very few noted occurrences of these populations (Dobson et al. 2014). It is likely however that, as AMPs are become a common treatment option, more populations of pathogenic bacteria will also become resistant. When all else fails, specifically antibiotics and AMPs, there is still another option that is being studied for treating resistant strains of bacteria. This newer treatment involves fighting fire with fire. The way that researchers are doing this is by infecting pathogenic bacteria with their own viruses, more specifically, bacteriophages. Bacteriophages, also known simply as phages, are precisely bacterial viruses that infect bacteria by disrupting pathogenic bacterium lytic cycles (Sulakvelidze et al., 2001). By disrupting the lytic cycles of bacterium, phages destroy their metabolism, which eventually results in the cell’s death (Sulakvelidze et al., 2001). Phages will insert their DNA into the bacterium, allowing their DNA to be transcribed. Once their DNA is transcribed the cell will proceed to make new phages and as soon as they are ready to be released, the cell will lyse (Sulakvelidze et al., 2001). One of the worries about using phages to fight pathogens is that the phages will infect “good” bacteria, or the bacteria that are important in the everyday function of human beings. However, studies have proven that phages are very specific when they target bacteria, which makes researchers confident that bacteriophage therapy is the definite route to defeating antibiotic resistant bacteria (Sulakvelidze et al. 2001). An experiment was conducted with canines recently to test whether or not phages were capable of this type of specific therapy. For this study 10 dogs who were infected with Pseudomonas aeruginosa otitis, an infection of the ear, were each dosed with bacteriophage populations that were active against the bacterium in which the dogs were infected (Hawkins et al., 2010). After the dosage, two days later, the dogs’ ear infections were observed and noted. The team of researchers was able to positively correlate the bacteriophage therapy with the lysing of the Pseudomonas aeruginosa otitis (Hawkins et al. 2010). This proved that even though a population of bacterium may be resistant to antibiotics, the population might still succumb to phage therapy. Phage therapy continues to be tested through clinical trials and looks to be the light at the end of the tunnel for a new way to fight antibiotic resistant pathogens. A natural defense to pathogenic bacterial infections, without the use of antibiotics, AMP therapy or phage therapy, lies in the immune system. One’s immune system is comprised of many different types of “good” bacteria that are found throughout the body. The gastrointestinal tract is a specific area in which some microbiota that are important for immune response are found (Ubeda 2012). When antibiotics are administered in high quantities, there can be a negative effect in the immune system because some of the microbiota that is essential for the immune system are destroyed (Ubeda 2012). In fact, researchers found that after completing a five-day study of administering an antibiotic into human subjects the antibiotic decreased the efficiency of the bacteria in the gastrointestinal tract (Ubeda 2012). This study concluded by pointing out that while antibiotics are being administered, around one third of bacterial populations important for the human immune system were altered, decreasing their ability to fight infections (Ubeda 2012). For example, amoxicillin, a commonly used antibiotic drug, sufficiently eliminated Lactobacillus spp, a lactic acid bacteria, in the intestinal tract (Ubeda 2012). Effective analysis of antibiotic effects on the microbiota in the gastrointestinal tract shows that antibiotics are efficient at destroying many bacteria that are important for the human immune system (Ubeda 2012). Antibiotic resistance research is very much prevalent today as there is a growing concern that antibiotics themselves will eventually lead to an era similar to when antibiotics were not invented yet, a time when antibiotics will no longer have any function. This threat of not being able to combat different types of fatal pathogens is a leading issue in modern medicine (Saver 2008). There have been recent ideas presented in order to decrease the overuse of antibiotics, such as changing patent rights for pharmaceutical companies to push them to discover new medicine or treatments, as well as influencing pharmaceutical companies to resist overselling of newer antibiotics (Saver 2008). Physicians also play a major role in the prevention of increasing antibiotic resistance by limiting the use of antibiotics by their patients (Saver, 2008). Antibiotics were once known as one of the greatest inventions known to man. However, today researchers fear that they may not be viable weapons to combat infections due to increasing resistance among populations of bacteria (Zaffiri 2012). There are many ways in which pathogenic bacteria can be fought, and there are many more ways yet to be discovered. Infections continue to take the lives of many people daily, so it is urgent that these other methods of combating pathogenic bacteria are discovered. Antibiotics continue to save the lives of many patients but also give rise to a more powerful, resistant bacteria. Antibiotic resistant bacteria forced the development of AMP and bacteriophage therapy as well as many other new strategies for combating pathogenic infections. As microbes continue to develop resistance to our treatments, it is our responsibility to make we use antibiotics correctly to ensure the discontinuation of the superbugs. --	References: --- Lederberg, J. 2000. Infectious History. Science Vol. 288 no. 5464 pp. 287-293

Davies, J., Davies, D. 2010. Origins and Evolution of Antibiotic Resistance; Microbiol Mol Biol Rev. 74(3): 417–433.

Dobson, A. J., Purve, J., Rolff. J. 2014. Increased survival of experimentally evolved  antimicrobial peptide-resistant Staphylococcus aureus in an animal host. Evolutionary Applications.

Saver R. 2008. In Tepid Defense of Population Health: Physicians and Antibiotic Resistance. American Journal Of Law & Medicine [serial online]. 34(4):431-491. Available from: Health Source: Nursing/Academic Edition, Ipswich, MA.

Ubeda C, Pamer E. 2012. Antibiotics, microbiota, and immune defense. Trends In Immunology [serial online].33(9):459-466. Available from: Academic Search Premier, Ipswich, MA.

Hawkins. C., Harper, D., Burch, D., Änggård, E., Soothill. J. 2010Topical treatment of Pseudomonas aeruginosa otitis of dogs with a bacteriophage mixture: A before/after clinical trial. Veterinary Microbiology. Volume 146, Issues 3–4, Pages 309–313.

Zaffiri L, Gardner J, Toledo-Pereyra L. 2012. History of antibiotics. From salvarsan to cephalosporins. Journal Of Investigative Surgery: The Official Journal Of The Academy Of Surgical Research [serial online];25(2):67-77. Available from: MEDLINE with Full Text, Ipswich, MA.

Sulakvelidze, A., Alavidze, Z., Morris, Jr J. G., 2001. Bacteriophage Therapy. Antimicrob Agents Chemother. 45(3): 649–659.