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            <h1>Antibiotics resistance – a big, global challenge</h1>
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                Antibiotic resistance is poised to become one of the greatest dangers of our time. Since its discovery
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                in 1928, antibiotics have been our first line of defense against bacterial infections. Antibiotics have
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                saved countless lives, and made difficult and complex surgeries possible [1]. For half a century we have
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                enjoyed the golden age of antibiotics where we have had no reason to fear bacterial infections. But this
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                golden age is coming to an end. Widespread misuse of antibiotics, coupled with minimal investment in new
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                treatments have allowed pathogenic bacteria to develop resistances to many antibiotics. Our best defense
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                against the bacteria have now created one of our greatest medical threats. [2]
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                        The Infectious Disease Society of America (IDSA) have confirmed that the United States and the
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                        rest of the world are amid an emerging crisis of antibiotic resistance for microbial pathogens
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                        [2]. In 2016 the World Health Organization (WHO) stated that antibiotic resistance is one of the
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                        biggest threats to global health, food security, and development today. [3]
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                        <br><br>
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                        As antibiotics are losing their effect, invasive surgeries such as organ transplants, joint
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                        replacements and cardiac surgeries will become difficult and expensive. People undergoing
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                        chemotherapy or taking any immunosuppressants will be in a lot more danger of contracting
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                        deadly infections. An increasing number of infections, such as pneumonia, gonorrhea and
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                        tuberculosis, are becoming difficult to treat because the antibiotics previously used are
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                        starting to become less effective [3]. The threat of antibiotic resistance has led to policies
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                        for restrictive use of antibiotics, but many countries have already given up the battle against
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                        certain antibiotic resistant bacteria, such as MRSA (Methicillin-resistant Staphylococcus aureus),
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                        common in hospitals. If these policies fail, the need for an alternative will be vital.
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                <h3 class="content_subtitle" style="text-align:center">Title</h3>
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                    Smart Yogurt：A possible alternative supply of two liver-protective factors with
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                    colonization-prone <i>Lactococcus lactisa</i>
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                <h3 class="content_subtitle" style="text-align:center">Abstract</h3>
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            <h1>Bacteriophages as an alternative to antibiotics</h1>
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                    A variety of liver diseases occur throughout the world irrespective of age, sex, region or
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                Fortunately, antibiotics are not the only natural enemies of bacteria. Bacteriophages, or phages for
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                    race. Two important liver-protective factors (glutathione and S-adenosyl methionine) has been
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                short, are tiny, bacteria-specific viruses capable of infecting selected bacteria while leaving other
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                    applied to prevent and treat many different liver diseases and damage. Due to low stability and
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                bacteria, as well as animal and plant cells, unharmed. They are one of the most widespread biological
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                    short half-life, oral table supply of GSH or SAM might be replaced by a novel strategy of
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                units in the biosphere, and exist anywhere bacteria can be found, for instance in soil, water and animal
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                    supplying these molecules continuously using our synthetic biology design of smart yogurt. In
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                intestines. In nature there is a continuous battle between phages and bacteria, with the consequence
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                    the experiment, two-functional GSH synthetase gene (<i>gshF</i>) and SAM synthetase gene (<i>metK</i>) were
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                that for every bacterium there probably exists one bacteriophage capable of killing it. Bacteriophages
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                    in tandem inserted into the expression vector (pNZ8148), and the resulted plasmid (pNZ-GM) was
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                might therefore be an interesting topic to look into in the search for alternatives to antibiotics.
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                    further employed to construct the target vector pNZ-GMcA by introducing adhesion factor gene
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                    (<i>cwaA</i>). This target vector was confirmed by gene sequencing and transformed into food-grade
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                    <i>Lactococcus lactis</i>. Further studies showed that the synthetic levels of SAM and GSH were
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                    improved greatly with <i>Lactococcus lactis</i> NZ9000/pNZ-GMcA, and the colonization-prone ability
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                    was also increased simultaneously. Finally, this recombinant <i>Lactococcus lactis</i> was inoculated
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                    to produce our smart yogurt separately or combined with <i>Lactobacillus delbruecki</i>. The present
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                <p class="show_more">Show more</p>
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                    work paved one road to supply liver-protective agents using smart yogurt concept thanks to
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                <img src="https://static.igem.org/mediawiki/2017/7/72/T--NTNU_Trondheim--arrow_down_grey.png">
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                    synthetic biology.
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                        The bacteriophages were discovered in the beginning of the 20th century, and scientists early
 
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                        suggested using them to counter bacterial infections. With the discovery of antibiotics, however,
 
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                        scientists in the Western world lost the interest in bacteriophages, and the research on phages
 
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                        was primarily conducted in the Soviet union, especially in what is now the country of Georgia.
 
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                        During the second world war, Soviet soldiers used bacteriophages as treatment for infections,
 
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                        and there still exists a phage therapy center in Tbilisi, Georgia today [4]. Phage therapy had
 
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                        a bad reputation for a long time, mostly because of poor documentation and research methods,
 
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                        but currently, under the threat of antibiotic resistance, the interest in bacteriophages is
 
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                        rising once again.[5]
 
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                        <br><br>
 
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                        Phage therapy does however have several issues to be ironed out before becoming a mainstream
 
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                        medical treatment.[5] One major stumbling block for phage therapy is the high host specificity
 
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                        of phages. Most phages can only infect certain strains of a bacterial species. This creates the
 
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                        need for either large libraries of potential phages, or a quick method of developing a phage
 
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                        capable of fighting a given bacterial infection. In order to solve this problem, our project
 
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                        attempts to investigate the latter method.
 
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            <h1>References</h1>
 
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            <p>
 
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                [1] Golkar, Z., Bagasra, O., Pace, D. G. (2014). Bacteriophage therapy: a potential solution for the antibiotic resistance crisis. J infect Dev Ctries, 8(2), 129-136. doi: 10.3855/jidc.3573
 
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                <br><br>
 
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                [2] Infectious  Diseases  Society  of  America  (2004) Bad  bugs,  no drugs:  as antibiotic  discovery  stagnates,  a  public health  crisis brews.  Alexandria,  Infectious  Diseases  Society  of  America. Available at http://www.fda.gov/ohrms/dockets/dockets/04s0233/04s-0233-c000005-03-IDSA-vol1.pdf
 
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                <br><br>
 
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                [3] World Health Organization (2017). Antibiotic resistance. Available at: http://www.who.int/mediacentre/factsheets/antibiotic-resistance/en/
 
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                <br><br>
 
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                [4] Phage therapy center (2000-2017). Available at:
 
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                https://www.phagetherapycenter.com/pii/PatientServlet?command=static_home
 
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                <br><br>
 
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                [5] Sulakvelidze, A., Alavidze, Z., Morris, J. G. (2001). Bacteriophage Therapy. Antimicrob Agents Chemother, 45(3), 649-659. doi: 10.1128/AAC.45.3.649-659.2001
 
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Latest revision as of 03:04, 18 October 2018

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Title

Smart Yogurt：A possible alternative supply of two liver-protective factors with colonization-prone Lactococcus lactisa

Abstract

A variety of liver diseases occur throughout the world irrespective of age, sex, region or race. Two important liver-protective factors (glutathione and S-adenosyl methionine) has been applied to prevent and treat many different liver diseases and damage. Due to low stability and short half-life, oral table supply of GSH or SAM might be replaced by a novel strategy of supplying these molecules continuously using our synthetic biology design of smart yogurt. In the experiment, two-functional GSH synthetase gene (gshF) and SAM synthetase gene (metK) were in tandem inserted into the expression vector (pNZ8148), and the resulted plasmid (pNZ-GM) was further employed to construct the target vector pNZ-GMcA by introducing adhesion factor gene (cwaA). This target vector was confirmed by gene sequencing and transformed into food-grade Lactococcus lactis. Further studies showed that the synthetic levels of SAM and GSH were improved greatly with Lactococcus lactis NZ9000/pNZ-GMcA, and the colonization-prone ability was also increased simultaneously. Finally, this recombinant Lactococcus lactis was inoculated to produce our smart yogurt separately or combined with Lactobacillus delbruecki. The present work paved one road to supply liver-protective agents using smart yogurt concept thanks to synthetic biology.