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EEOB 3310 recitation: Tues 10:20am TA: Matt Holding

Link, added sentence, citation, and three suggestions: Due: 10/1''' ''' https://en.wikipedia.org/wiki/Emerging_infectious_disease

Added sentence: Nosocomial infections, such as MRSA are emerging in hospitals, and extremely problematic in that they are resistant to many antibiotics.[3] Citation:  Witte, W (1997). "Increasing incidence and widespread dissemination of methicillin‐resistant Staphylococcus aureus (MRSA) in hospitals in central Europe, with special reference to German hospitals.". Clinical Microbiology and Infection 3 (4): 414 Extra |pages= or |at= (help). Suggestions: There are a few suggestions that I would make for this article. First; there are numerous emerging infectious diseases that are not listed; although HIV/AIDS is a predominate disease, it is not the only one. A very important and relevant emerging disease that you could include is MRSA.

Secondly you could tie in which factors mostly affect which disease, or contribute to its emergence or reemergence, and possibly ways that have been proposed to combat these factors.

Finally, I would add more on MRSA and how and its relevance in hospitals, and how it differs from the rest of the emerging diseases because it is primarily acquired in a hospital, making it different from others.

annotated bibliography: Priya Nalluri TA: Matt Holding Tuesday 10:20am recitation

Topic: The evolution of MRSA (methicillin-resistant Staphylococcus aureus)

Harris, S. R., Feil, E. J., Holden, M. T., Quail, M. A., Nickerson, E. K., Chantratita, N., & Bentley, S. D. (2010). Evolution of MRSA during hospital transmission and intercontinental spread. Science, 327(5964), 469-474. In this this article the authors seek to better understand the evolution of MRSA, and to propose a better method of understanding the evolution. The methods they used were whole genome sequencing. By using whole genome sequencing, they were better able to map the single nucleotide polymorphisms (SNP) that would explain the evolution of MRSA throughout the years. Most importantly, these scientists were able to determine a time frame from which MRSA developed and where certain genes in the antibacterial resistant bacteria originated. This article would be necessary for me to cite since it discusses the origins of the MRSA and subsequent changes it has undergone, which are key ideas in paper.

Enright, M. C., Robinson, D. A., Randle, G., Feil, E. J., Grundmann, H., & Spratt, B. G. (2002). The evolutionary history of methicillin-resistant Staphylococcus aureus (MRSA). Proceedings of the National Academy of Sciences, 99(11), 7687-7692. This article was written earlier on in MRSA’s history, when it was less understood. In this article the authors wanted to better understand the original clones of MRSA, and establish a logical, standard nomenclature for MRSA. In their experiment they used a multilocus sequencing system, called BURST, to sequence patterns in the genome of different strains of MRSA. They were able to identify the original clones from which the most virulent strains of MRSA originated as well as propose a standard nomenclature for these different strains. Although their experiment was well designed, I would have probably would have suggested using a whole genome sequencing technique since it would better allow them to compare differences on a nucleotide level and give them a better idea of the evolution of MRSA since it seemed to work well for other scientists in their experiments with MRSA.

Benson, M. A., Ohneck, E. A., Ryan, C., Alonzo, F., Smith, H., Narechania, A., & Torres, V. J. (2014). Evolution of hypervirulence by a MRSA clone through acquisition of a transposable element. Molecular microbiology, 93(4), 664-681. In this article the scientists wanted to better understand the origins of virulent traits MRSA. They used whole genome sequencing of multiple MRSA isolates. In their experiment they found several key virulent factors that made certain strains of MRSA antibiotic resistant and more virulent than the average case of Staphylococcus aureus (many people are carriers). They were able to pinpoint where the antibacterial resistance gene came from (which plasmid and location) which was a major finding of the study. It would be necessary for me to cite this in my own writings since the article points out the origin of certain virulence factors that makes MRSA such a problem in hospitals, which are key points in the evolution of it as a infectious disease.

Witte, W., Kresken, M., Braulke, C., & Cuny, C. (1997). Increasing incidence and widespread dissemination of methicillin‐resistant Staphylococcus aureus (MRSA) in hospitals in central Europe, with special reference to German hospitals. Clinical Microbiology and Infection, 3(4), 414-422. The main purpose of this article was to collect and present data on the prevalence of MRSA in hospitals and different factors associated with it. They collected a wide range of MRSA isolates from hospital-acquired infections; they then used PCR to amplify certain stretches of the genome. Overall they found that MRSA infections had increased by a significant number in hospitals over a 5 year period, but most importantly it they found that a mecA gene was associated with the methicillin-resistant version that was not found in the methicillin-susceptible versions of the pathogen. This article would be important for me to cite because it identifies a factor that differentiates MRSA from it’s less dangerous relative, and suggests that MRSA evolved from MSSA (Methicillin-susceptible Staphylococcus aureus).

Strommenger, B., Bartels, M. D., Kurt, K., Layer, F., Rohde, S. M., Boye, K., Nübel, U. (2013). Evolution of methicillin-resistant Staphylococcus aureus towards increasing resistance. Journal of Antimicrobial Chemotherapy, 413. The main purpose of this experiment was a desire to better understand the evolutionary history of Staphylococcus aureus, Because MRSA, which is part of the S. aureus family, causes many problems in hospital settings. Their methods consisted of creating a phylogeny based on multiple isolates that they collected. They followed certain genes and mutations in order to create their tree. They discovered 9 different clades within their phylogeny, but most importantly they were able to discover 8 independent events of when S. aureus acquired methicillin resistance, and traced the original clone of the methicillin-resistant variant to a single clone from the 1970’s. This finding is absolutely key in my paper since it proposes a specific origin of MRSA and also proposed phylogenies, making it necessary to cite in my own writings.

Link to page:

https://en.wikipedia.org/wiki/Emerging_infectious_disease

Addition to page:

An example of this is MRSA, a common nosocomial infection. MRSA, the pathogen that we know today, evolved from Methicillin-susceptible Staphylococcus aureus (MSSA) otherwise known as common S. Aureus. Many people are natural carriers of S. Aureus, without being affected in any way, shape, or form. MSSA was treatable with the antibiotic methicillin until it acquired the gene for antibiotic resistance. Though genetic mapping of various strains of MRSA, scientists have found that MSSA acquired the mecA gene in the 1960s, which accounts for its pathogenicity, before this it had a predominantly commensal relationship with humans. It is theorized that when this S. Aureus strain that had acquired the mecA gene was introduced into hospitals, it came into contact with other hospital bacteria that had already been exposed to high levels of antibiotics. (Witte et al., 1997) When exposed to such high levels of antibiotics, the hospital bacteria suddenly found themselves in an environment that had a high level of selection for antibiotic resistance, and thus resistance to multiple antibiotics formed with in these hospital populations. When S. Aureus came into contact with these populations, the multiple genes that code for antibiotic resistance to different drugs were then acquired by MRSA, making it nearly impossible to control (Benson et al., 2014). It is thought that MSSA acquired the resistance gene through the horizontal gene transfer, a method in which genetic information can be passed within a generation, and spread rapidly through its own population as was illustrated in multiple studies. Horizontal gene transfer speeds the process of genetic transfer since there is no need to wait an entire generation time for gene to be passed on. Since most antibiotics do not work on MRSA, physicians have to turn to alternative methods based in Darwinian medicine. However prevention is the most preferred method of avoiding antibiotic resistance. By reducing unnecessary antibiotic use within society as a whole, antibiotics resistance can be slowed.

Final Paper:

MRSA and The Evolution of Antibiotic Resistance Modern medicine has drastically changed health, life expectancy, and quality of life. This became especially true in 1945 when penicillin, the first antibiotic was discovered and in put into widespread use. Life expectancy increased dramatically and suddenly there was a cure for many dreaded diseases that were formerly incurable, such as; the plague, venereal diseases, infections, and much more. Antibiotics changed the world. However, our misuse of antibiotics has potentially created our downfall. Antibiotic resistant bacteria have emerged, immune to many of the antibiotics we employ against them. Staphylococcus aureus is a common microorganism found on the skin of many people. However in the past few decades an antibiotic resistant strain has risen; known as methicillin-resistant Staphylococcus aureus (MRSA). This strain, found most commonly in hospitals has become immune to many of the most powerful antibiotics available. But by employing evolutionary concepts, scientists have found a way to curtail MRSA (Enright et al., 2002). In this paper we will discuss evolution leading to one of the most notorious nosocomial infections yet, and the evolutionarily-based control concepts used to keep MRSA in check. Despite common perception, bacteria are not entirely harmful to humans. The average healthy human adult can have anywhere from 3-5 lbs of bacterial in their bodies alone. Humans have benefited greatly from this mutualistic relationship with bacteria. Bacteria co-evolved with humans, as there was strong selection for bacteria that could form mutualistic interactions that benefited the human body. The bacteria in our digestive systems protect us from pathogenic bacteria that would be harmful to us by competing for binding sites and resources. They also help in the absorption of nutrients, the manufacturing of vitamins that we cannot synthesize ourselves, as well as having several benefits to the immune system. In return, humans provide bacteria with a home, nutrients and protection from outside elements (Dethlefsen et al., 2007). There are thousands of different types of bacteria in the average human. Among the bacteria that can be found in humans is Staphylococcus aureus. Usually S. Aureus doesn’t cause symptoms in healthy people, however it can become a problem in people who are admitted into the hospital and are already ill. Since MRSA is commonly categorized as a nosocomial infection, it is most frequently acquired in hospital settings. Usually infections caused by S. Aureus are revolved by simply administering antibiotics, but MRSA is a special strain of S. Aureus that has acquired immunity to methicillin, an antibiotic as well as many other antibiotics. This is not surprising since more and more bacteria have been gaining resistance to antibiotics due to a multitude of evolutionary factors. Bacteria themselves are ideal for studying evolution because they can evolve so quickly. This is boosted by short generation times and ability to replicate prolifically. Another factor that allows them to evolve so well is horizontal gene transfer. This is not the same as vertical transmission, which also plays a role. (Strommenger et al., 2013) Usually there are selective pressures in the environment that favor certain traits over others in organisms. Organisms that display those favored traits are more likely to survive to adulthood and then pass on those favored traits to their offspring. The same applies when there is a mutation in the organism’s DNA and suddenly a new advantageous trait is present. That trait will also be passed on to the next generation. This is known as vertical transmission, where genes are passed from one generation to the next. Vertical gene transmission is what we might be more familiar with, since that is how most mammals and other animals pass genetic information to another. This way is also how MRSA bacteria that have the gene for antibiotic resistance will pass it on to it’s offspring, or daughter cells that result from binary fission. However vertical transmission is not the only way bacteria pass on advantageous traits. Horizontal transmission is common amongst bacteria, although not yet proven to be unique to bacteria, and MRSA is no different. In Krishnapillai’s study, he illustrates how horizontal gene transfer allows bacteria to pass down genes within the same generation. Besides carrying genetic information in chromosomes, bacteria also carry genes in plasmids, which often carry “non-essential” genes. It is the genetic information stored in the plasmids that they are able to pass between each other. They can even take the genes from the plasmid, and incorporate it into their own genome, which would then be passed down to their descendants (Krishnapillai 1996). This creates quite a lot of genetic variation which is advantageous in variable environments, and the human body is nothing, if not a highly variable environment. Horizontal gene transfer is highly beneficial to the evolution of MRSA in that MRSA does not need to wait for a mutation to occur independently in one organism and then wait for its descendants to proliferate. For example, the gene for antibiotic resistance could arise in one organism, and then spread very quickly through the population. It is important to understand that MRSA evolved from Methicillin-susceptible Staphylococcus aureus (MSSA) otherwise known as common S. Aureus. This strain, MSSA, was treatable with the antibiotic methicillin until it acquired the gene for antibiotic resistance. In his study, Witte mapped the genetic sequence of multiple different strains of MRSA in order to better understand its origins. He discovered that soon after the advent of antibiotics, MRSA soon acquired the mecA gene in the 1960s, which accounts for its resistance to certain antibiotics. It is theorized that then this S. Aureus strain that possessed the mecA gene was introduced into hospitals, it came into contact with other hospital bacteria that had already been exposed to high levels of antibiotic. (Witte et al., 1997) When exposed to such high levels of antibiotics, the hospital bacteria suddenly found themselves in an environment that had a high level of selection for antibiotic resistance, and thus resistance to multiple antibiotics formed with in these hospital populations. Since plasmids can carry up to several different genes at once, when S. Aureus came into contact with these populations, the multiple genes that code for antibiotic resistance to different drugs were then acquired by MRSA, making it nearly impossible to control (Benson et al., 2014). It is thought that MSSA acquired the resistance gene through the horizontal gene transfer and spread rapidly through its own population as illustrated in Krishnapillai’s study. Scientists and doctors have since employed multiple strategies to try and cure patients infected with MRSA. Since MRSA quickly acquires immunity to many antibiotics if it is not already resistant to begin with, it can be very difficult to treat. That is why many doctors are turning to evolutionary concepts to treat MRSA. One treatment is alternating antibiotics. Patients are given two different types of antibiotics, alternatively. The first type of antibiotics wipes out part of the population, and then the second antibiotic is administered. The second antibiotic then eliminates the genotype that may have been gaining resistance to the first antibiotic, then first antibiotic is used again to eliminate genotypes that may have been conferring resistance to the second antibiotic, and so on. This treatment relies on the idea that with constantly changing selection pressures, the organisms will not be able to develop resistance to either drug, because one it gains resistance to Drug 1, the alternative drug will be administered and the bacteria populations that conferred resistance to Drug 1 will die off. Then the patient would be switched back to Drug 1 and the populations that acquired resistance to Drug 2 will die off, and the infection will become controlled (Nye 2013). However treating the source of antibiotic resistance would be more effective. Up until recently, many doctors over prescribed antibiotics without knowing the consequences. This has lessened antibiotic’s effect on infections and given rise to resistant strains of bacteria. (Harris et al., 2010) If you remove the pressure from the environment, there is no need for the gene to have an advantage and gain a foothold in the population in the first place. This can also be achieved by limiting use of antibacterial agents when they are unnecessary and promoting good hygiene to prevent disease and need to use antibiotics in the first place. Evolutionary concepts can explain and predict many phenomenons that we see today. Although humans have co-evolved with many types of bacteria and formed mutualistic relationships with them, there are bacteria that have not and are pathogenic to us. MRSA did not begin that way, in fact many people have S. Aureus as a part of their normal skin flora, and it is not pathogenic to most. However, long ago in its evolutionary past, S. Aureus acquired a gene for antibiotic resistance and pathogenicity that affect many already ill patients in hospitals. Nevertheless this outcome was foreseen by scientist many years ago. Even two decades ago, scientists were predicting strains of MRSA that we have now come to see pass. Through horizontal transmission, MRSA is able to acquire resistance genes and spread those genes through the population quickly. MRSA is on the rise and treatments are limited since producing a new antibiotic takes many years, is very costly, and a pathogen can develop resistance to it in a fraction of the time it takes to produce the new antibiotic. So instead, doctors are turning to methods that draw from evolutionary concepts to treat cases of MRSA, such as alternating antibiotic treatments, and trying to prevent the selection pressures that select for antibiotic resistance in bacteria. Initial studies have found these treatments to be successful, however it is not a long-term solution. Hopefully, however, in the future there will be more research put into alternative methods to antibiotics that will successfully overcome the issue of antibiotic resistance.

References

Harris, S. R., Feil, E. J., Holden, M. T., Quail, M. A., Nickerson, E. K., Chantratita, N., & Bentley, S. D. (2010). Evolution of MRSA during hospital transmission and intercontinental spread. Science, 327(5964), 469-474.

Enright, M. C., Robinson, D. A., Randle, G., Feil, E. J., Grundmann, H., & Spratt, B. G. (2002). The evolutionary history of methicillin-resistant Staphylococcus aureus (MRSA). Proceedings of the National Academy of Sciences, 99(11), 7687-7692.

Benson, M. A., Ohneck, E. A., Ryan, C., Alonzo, F., Smith, H., Narechania, A., & Torres, V. J. (2014). Evolution of hypervirulence by a MRSA clone through acquisition of a transposable element. Molecular microbiology, 93(4), 664-681.

Witte, W., Kresken, M., Braulke, C., & Cuny, C. (1997). Increasing incidence and widespread dissemination of methicillin‐resistant Staphylococcus aureus (MRSA) in hospitals in central Europe, with special reference to German hospitals. Clinical Microbiology and Infection, 3(4), 414-422.

Strommenger, B., Bartels, M. D., Kurt, K., Layer, F., Rohde, S. M., Boye, K., Nübel, U. (2013). Evolution of methicillin-resistant Staphylococcus aureus towards increasing resistance. Journal of Antimicrobial Chemotherapy, 69(3), 413.

Dethlefsen, L., McFall-Ngai, M., & Relman, D. A. (2007). An ecological and evolutionary perspective on human–microbe mutualism and disease. Nature,449(7164), 811-818.

Krishnapillai, V. (1996). Horizontal gene transfer. Journal of Genetics, 75(2), 219-232.

Nye, B. D. (2013). The Evolution of Multiple Resistant Strains: An Abstract Model of Systemic Treatment and Accumulated Resistance. Journal of Artificial Societies and Social Simulation, 16(4), 2.