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                        <h1 class="title">Project Background</h1>
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<!--
 +
                        <p class="paragraph">MRSA is an acronym for the pathogen Staphylococcus aureus. MRSA developed resistance to β-lactam antibiotics in a large extent. Currently the methicillin resistance has been widely used as an indication for the β-lactam resistant phenotype of this pathogen.
 +
As a micro-organism in Staphylococcus genus, which are Gram-positive cocci, MRSA is usually found in a skin colonized by bacteria and in nasal passages of many healthy people. They stay as carriage state in healthy people’s skin flora, and there are two predominant species: Staphylococcus epidermidis and S. aureus, which refers to the major pathogens among the staphylococci.</p>
 +
                        <p class="paragraph">MRSA is an ovoid-shaped bacterium with a thick cell wall of peptidoglycan and accessory polymers. It has both complex DNA structure and typical prokaryotic DNA replication machinery enzymes. It complements a large amount of ribosomal proteins in our body. As it grows, they grow in crumps to form a grape-shape. Since it is a gram positive pathogen, it stains purple after Gram-staining.</p>
 +
                        <p class="paragraph">MRSA is everywhere. It produces virulence factors by selecting spontaneous mutant variants under external stress, expressing pre-existing genetic resistance determinants, or acquiring resistance elements. These factors allow the MRSA adapt to the harsh environments and stay in a hardy microbial life form.  It is an “opportunistic pathogen” which either doesn’t defend or use immunosuppression. MRSA has evolved to carry resistance determinants encoding an additional penicillin-binding protein with low affinity for beta-lactam antibiotics, efflux pumps, beta lactamases, multi-resistance factor encoded plasmids, and other resistance factors, regulatory elements, and virulence factors. Therefore people named MRSA as “superbug.”</p>
                         <p class="paragraph">
                         <p class="paragraph">
-
                            MRSA is an acronym for the pathogen Staphylococcus aureus. MRSA developed resistance to β-lactam antibiotics in a large extent. Currently the methicillin resistance has been widely used as an indication for the β-lactam resistant phenotype of this pathogen.
+
The first use of vancomycin in clinics happened during 1958. It has risen as a hope in the treatment of S. aureus strains that produce β-lactamase. However, this new medical technique was soon superseded by the new β-lactams. But as more people discovered and expanded the use of MRSA in clinic, by 1970s, beta-lactams were frequently replaced with vancomycin.</p>
-
As a micro-organism in Staphylococcus genus, which are Gram-positive cocci, MRSA is usually found in a skin colonized by bacteria and in nasal passages of many healthy people. They stay as carriage state in healthy people’s skin flora, and there are two predominant species: Staphylococcus epidermidis and S. aureus, which refers to the major pathogens among the staphylococci.
+
                        <p class="paragraph">This development, however, lead to another consequence: MRSA showed an increase in vancomycin resistance, especially in the enterococci and eventually in staphylococci. Hence the science had to question whether they should use the ‘right’ agent such as vancomycin, or not to use to prevent the collateral damage resistance. </p>
-
                      </p>
+
                        <p class="paragraph">Current empirical antibiotic hospital treatment options for MRSA are vancomycin, linezolid, quinupristin, dalfospristin, daptomycin; but there is limit in the use of these antibiotics.</p>
-
                      <p class="paragraph">
+
-->
-
                          MRSA is an ovoid-shaped bacterium with a thick cell wall of peptidoglycan and accessory polymers. It has both complex DNA structure and typical prokaryotic DNA replication machinery enzymes. It complements a large amount of ribosomal proteins in our body. As it grows, they grow in crumps to form a grape-shape. Since it is a gram positive pathogen, it stains purple after Gram-staining.
+
                        <img class="wiki_img" src="https://static.igem.org/mediawiki/2014hs/e/e4/Elan_vital_background_1.png" />
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                      </p>
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                        <p class="wiki_caption">Photo of MRSA taken using Scanning Electron Micrograph 10,000x magnification</p>
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                      <p class="paragraph">
+
                        <p class="paragraph">Staphylococcus aureus is a gram-positive bacterium in the genus staphylococcus. It is frequently found on the human respiratory tract and skin flora. S. aureus has a circular shape, and grows in clumps like a grape. S. aureus is not always pathogenic: it can be found on the skin a nasal flora of healthy people, and approximately 20% of the human population is thought to be a long term carrier of the bacteria<i class="green">*</i>. But it can cause disease by producing toxic proteins. The diseases caused by S. aureus ranges from minor skin infections such as pimples, impetigo, and boils to life threatening disease such as pneumonia, and meningitis. Some of these S. aureus developed resistance to beta-lactam antibiotics. To determine if a given strain of S. aureus has beta-lactam antibiotic resistance, scientists often use methicillin, a beta-lactam antibiotic. Because of this, the S. aureus that has beta-lactam antibiotic resistance is called Methicillin Resistant S. aureus (MRSA) and the S. aureus that does not have beta-lactam resistance is called Methicillin Sensitive S. aureus (MSSA).</p>
-
                          MRSA is everywhere. It produces virulence factors by selecting spontaneous mutant variants under external stress, expressing pre-existing genetic resistance determinants, or acquiring resistance elements. These factors allow the MRSA adapt to the harsh environments and stay in a hardy microbial life form.  It is an “opportunistic pathogen” which either doesn’t defend or use immunosuppression. MRSA has evolved to carry resistance determinants encoding an additional penicillin-binding protein with low affinity for beta-lactam antibiotics, efflux pumps, beta lactamases, multiresistance factor encoded plasmids, and other resistance factors, regulatory elements, and virulence factors. Therefore people named MRSA as “superbug.”
+
                        <img class="wiki_img" src="https://static.igem.org/mediawiki/2014hs/0/06/Elan_vital_Background2.png" />
-
                      </p>
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                        <p class="wiki_caption">S. aureus and the disease caused by it</p>
-
                      <p class="paragraph">
+
                        <p class="paragraph">The beta-lactam resistance of MRSA makes it difficult to treat with conventional medicine. MRSA first appeared about 50 years earlier, and has developed into a major clinical health issue since. MRSA is highly contagious, especially in hospitals where the weakened immune system makes patients an easy target for MRSA. In fact, MRSA is thought to be one of the five most common causes of nosocomial infections<i class="green">**</i>. because of these traits, MRSA is one of the most dangerous clinical problems. It was shown that simple methods such as washing hands and using sterile medical equipment led to significant improvements in nosocomial infections of MRSA (source) but that does not solve that fundamental problem of the multidrug resistance of MRSA.</p>
-
                          The first use of vancomycin in clinics happened during 1958. It has risen as a hope in the treatment of S. aureus strains that produce β-lactamase. However, this new medical technique was soon superseded by the new β-lactams. But as more people discovered and expanded the use of MRSA in clinic, by 1970s, beta-lactams were frequently replaced with vancomycin.
+
                        <img class="wiki_img" src="https://static.igem.org/mediawiki/2014hs/9/9a/Elan_vital_Background3.png" />
-
                      </p>
+
                        <p class="wiki_caption">2012 MRSA spread map of Europe by ECDC</p>
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                      <p class="paragraph">
+
                        <img class="wiki_img" src="https://static.igem.org/mediawiki/2014hs/1/16/Elan_vital_background_4.png" />
-
                          This development, however, lead to another consequence: MRSA showed an increase in vancomycin resistance, especially in the enterococci and eventually in staphylococci. Hence the science had to question whether they should use the ‘right’ agent such as vancomycin, or not to use to prevent the collateral damage resistance.  
+
                        <p class="wiki_caption">2012 MRSA spread graph of Europe by ECDC</p>
-
                      </p>
+
                        <p class="listing green">* Kluytmans J, van Belkum A, Verbrugh H (July 1997). "Nasal carriage of Staphylococcus aureus: epidemiology, underlying mechanisms, and associated risks". Clin. Microbiol. Rev. 10 (3): 505–20. PMC 172932. PMID 9227864.</p>
-
                      <p class="paragraph">
+
                        <p class="listing green">** Bowersox, John (27 May 1999). "Experimental Staph Vaccine Broadly Protective in Animal Studies". NIH. Archived from the original on 5 May 2007. Retrieved 28 July 2007.</p>
-
                          Current empirical antibiotic hospital treatment options for MRSA are vancomycin, linezolid, quinupristin, dalfospristin, daptomycin; but there is limit in the use of these antibiotics.
+
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                    <p>&copy;2014 Elan Vital</p>
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Latest revision as of 12:11, 19 June 2014

Project Background

Photo of MRSA taken using Scanning Electron Micrograph 10,000x magnification

Staphylococcus aureus is a gram-positive bacterium in the genus staphylococcus. It is frequently found on the human respiratory tract and skin flora. S. aureus has a circular shape, and grows in clumps like a grape. S. aureus is not always pathogenic: it can be found on the skin a nasal flora of healthy people, and approximately 20% of the human population is thought to be a long term carrier of the bacteria*. But it can cause disease by producing toxic proteins. The diseases caused by S. aureus ranges from minor skin infections such as pimples, impetigo, and boils to life threatening disease such as pneumonia, and meningitis. Some of these S. aureus developed resistance to beta-lactam antibiotics. To determine if a given strain of S. aureus has beta-lactam antibiotic resistance, scientists often use methicillin, a beta-lactam antibiotic. Because of this, the S. aureus that has beta-lactam antibiotic resistance is called Methicillin Resistant S. aureus (MRSA) and the S. aureus that does not have beta-lactam resistance is called Methicillin Sensitive S. aureus (MSSA).

S. aureus and the disease caused by it

The beta-lactam resistance of MRSA makes it difficult to treat with conventional medicine. MRSA first appeared about 50 years earlier, and has developed into a major clinical health issue since. MRSA is highly contagious, especially in hospitals where the weakened immune system makes patients an easy target for MRSA. In fact, MRSA is thought to be one of the five most common causes of nosocomial infections**. because of these traits, MRSA is one of the most dangerous clinical problems. It was shown that simple methods such as washing hands and using sterile medical equipment led to significant improvements in nosocomial infections of MRSA (source) but that does not solve that fundamental problem of the multidrug resistance of MRSA.

2012 MRSA spread map of Europe by ECDC

2012 MRSA spread graph of Europe by ECDC

* Kluytmans J, van Belkum A, Verbrugh H (July 1997). "Nasal carriage of Staphylococcus aureus: epidemiology, underlying mechanisms, and associated risks". Clin. Microbiol. Rev. 10 (3): 505–20. PMC 172932. PMID 9227864.

** Bowersox, John (27 May 1999). "Experimental Staph Vaccine Broadly Protective in Animal Studies". NIH. Archived from the original on 5 May 2007. Retrieved 28 July 2007.