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| #top_title{ | | #top_title{ |
| display: none; | | display: none; |
− | } body{
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| } | | } |
− | .tab { margin-left: 40px; } | + | #content{ |
− | /* non numbered lists */
| + | width: 100%; |
− | .igem_2019_team_content .igem_2019_team_column_wrapper ol, .igem_2019_team_content .igem_2019_team_column_wrapper ol {
| + | } |
− | font-size: 100%;
| + | .body-background{ |
− | font-family: Arial, Helvetica, sans-serif;
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− | padding: 5px 0px;
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− | text-align: left;
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− | color: #484848;
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− | }
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− | </style>
| + | |
− | </head>
| + | |
− | <body>
| + | |
| | | |
− | <div class="container">
| + | width:100%; |
− | <h2>Problem</h2>
| + | height: 450px; |
− | <p>
| + | text-align: center; |
− | <i>Staphylococcus aureus</i> is a type of bacteria commonly found in hospitals, sports facilities,
| + | border-radius: 20px; |
− | and even the bodies of healthy individuals (1). As many as one third of the population carries
| + | opacity: 0.8; |
− | <i>S. aureus</i> in their nose, and about 20% of people carry <i>S. aureus</i> on the skin (1). While <i>S. aureus</i>
| + | background: url("https://2rdnmg1qbg403gumla1v9i2h-wpengine.netdna-ssl.com/wp-content/uploads/sites/3/2017/10/mrsa-650x450.jpg"); |
− | does not normally cause severe problems, it can cause infections of the skin, blood, and soft tissues,
| + | background-position: center; |
− | with approximately 20,000 deaths reported in the United States in 2017 as a result of <i>S. aureus</i> infection (2).
| + | background-size:cover ; |
− | Methicillin-resistant <i>Staphylococcus aureus</i>, or MRSA, is a potent strain of <i>S. aureus</i> that is resistant to
| + | background-repeat: no-repeat; |
− | common antibiotic treatments (1). This resistance to conventional treatment makes MRSA infections difficult to
| + | } |
− | combat, turning <i>S. aureus</i> into a much more deadly pathogen. To overcome antibiotic resistance, the medical
| + | |
− | community must find new ways to combat bacterial infection.
| + | |
− | </p>
| + | |
− |
| + | |
− |
| + | |
− | <h2>Inspiration</h2>
| + | |
− | <p>
| + | |
− | Our team was inspired by a 2013 paper by Hwang et al. titled “Reprogramming Microbes to be Pathogen-Seeking Killers” (3).
| + | |
− | Hwang et al. engineered <i>E. coli</i> to detect and fight <i>Pseudomonas aeruginosa</i> infections using a seek-and-kill technique.
| + | |
− | Their design is modular, which makes it possible to use their approach to target different bacteria. We found that the
| + | |
− | rise of antibiotic resistant bacteria makes it increasingly vital to find new treatments, which inspired us to adapt the
| + | |
− | system devised by Hwang et al. to target methicillin-resistant <i>Staphylococcus aureus</i>, or MRSA.
| + | |
− | </p>
| + | |
| | | |
− |
| + | .body-content{ |
− | <h2>Sensing</h2>
| + | position: relative; |
− | <p>
| + | width: 100%; |
− | Quorum sensing is a method of cell communication that uses small molecules to regulate gene expression (4). Gram-positive
| + | background-color: white; |
− | and Gram-negative use different small molecules to accomplish quorum sensing; Gram-positive species use autoinducing peptides
| + | height: auto; |
− | (AIP) while Gram-negative species use acyl homoserine lactones (AHL) (4). Our target species, <i>Staphylococcus aureus</i>,
| + | padding-top: 50px; |
− | uses four forms of AIP in the accessory gene regulator (agr) quorum sensing system. In the agr system, the genes AgrA and
| + | } |
− | AgrC code for proteins that detect AIP produced by neighboring <i>S. aureus</i> and activate the P2 promoter in response (5).
| + | |
− | </p>
| + | |
− | <p>
| + | |
− | Our project builds on BBa_K1022100, a BioBrick that combines AgrA and AgrC from the agr sensing system with green
| + | |
− | fluorescent protein under a pBAD promoter. We found that the wild-type AgrA and AgrC proteins contain amino acids not
| + | |
− | present in BBa_K1022100, and we aim to modify and potentially improve the existing part by introducing these missing
| + | |
− | amino acids. The P2 promoter used in BBa_K1022100 is also missing base pairs found in the binding site region of the
| + | |
− | wild-type P2 sequence. We plan to reintroduce these binding sites by using a more complete P2 promoter sequence to
| + | |
− | improve GFP production in the original BioBrick. Lastly, SarA is a transcriptional activator found in <i>S. aureus</i>
| + | |
− | that is believed to activate expression of genes in the agr system (6). We will introduce the SarA gene to further
| + | |
− | improve the effectiveness of the agr system.
| + | |
− | </p>
| + | |
| | | |
− | <h2>Motility</h2>
| + | .page-content p, ul, li{ |
− | <p>
| + | font-size: 10pt; |
− | Chemotaxis is the movement of a cell towards or away from a chemical stimulus based on concentration, either from
| + | line-height: 1.5; |
− | high to low or from low to high (7). In our system, AIP will provide the chemical gradient necessary to move <i>E. coli</i>
| + | color: #595959; |
− | in the direction of <i>S. aureus</i>. Chemotaxis is influenced by the post-translation modulation of the CheY and CheZ
| + | } |
− | proteins; however, there is an issue of potential overexpression that can lead to the inhibition of chemotaxis (3).
| + | |
− | In order to combat this issue, we will be implementing a degron, a sequence of amino acids responsible for protein
| + | |
− | degradation, to control CheZ expression (3). We will attach the YbaQ degron to CheZ’s C-terminus, much like the
| + | |
− | application used by the Hwang et al. study in 2013 (3). To demonstrate the functionality of chemotaxis in our system,
| + | |
− | we will first use a pBAD promoter to trigger chemotaxis. If successful, we will replace the pBAD promoter with a P2
| + | |
− | promoter which is activated by the agr system. This will ignite chemotaxis in the presence of AIP, moving the <i>E. coli</i> towards <i>S. aureus.</i>
| + | |
− | </p>
| + | |
| | | |
− | <h2>Killing</h2>
| + | .col-xs-12 p{ |
− | <p>
| + | font-size: 15pt; |
− | Bacteriocins are small antimicrobial peptides (AMPs) produced by bacteria to kill or inhibit other bacteria.
| + | line-height: 1.5 |
− | Many AMPs are currently under study as potential alternatives to antibiotic treatment due to the rise of antibiotic
| + | } |
− | resistance. One such AMP is garvicin KS, a bacteriocin produced by <i>Lactococcus garvieae</i>, a bacterial species
| + | |
− | found in raw milk. Garvicin KS is effective against <i>S. aureus</i> and other Gram-positive bacteria, and is more potent
| + | |
− | than many other bacteriocins (8). Mature garvicin KS is composed of three polypeptides encoded by three genes:
| + | |
− | GakA, GakB, and GakC (9). By placing these genes into an <i>E. coli</i> chassis, we plan to use <i>E. coli</i> to produce
| + | |
− | garvicin KS. As <i>E. coli</i> is a Gram-negative bacterium, additional steps must be taken to ensure that the
| + | |
− | garvicin KS peptides can be secreted from the cell. We have chosen a novel signal peptide first constructed
| + | |
− | in a 2017 paper by Han et al. to assist with secretion of the garvicin KS peptides (10). This peptide tags
| + | |
− | proteins for secretion by the Sec pathway, a pathway used by <i>E. coli</i> to secrete proteins into the periplasm
| + | |
− | and outer membrane (10).
| + | |
− | </p>
| + | |
− | <h2>Impact</h2>
| + | |
− | <p>
| + | |
− | Our system has the potential to be used both in vivo and in vitro to combat MRSA planktonic cells and biofilms.
| + | |
− | Many bacteria produce biofilms, which are collections of cells attached to a surface and the extracellular matrix
| + | |
− | that encases these cells (11). Biofilms provide protection to the bacteria within and are often resistant to
| + | |
− | antibiotic treatment, which further compounds the issue of antibiotic resistance (12). One possible solution
| + | |
− | is the use of antimicrobial peptides such as garvicin KS, which have been shown to be more effective towards
| + | |
− | biofilms than traditional antibiotics (13). Our three module system first uses quorum sensing to detect AIP
| + | |
− | produced by MRSA biofilms and planktonic cells. Detection of AIP simultaneously triggers chemotaxis and the
| + | |
− | production of garvicin KS. The use of chemotaxis allows our <i>E. coli</i> to seek out and move towards biofilms and
| + | |
− | planktonic cells, releasing garvicin KS near the source and maximizing effectiveness. Potential applications
| + | |
− | of the system include detecting and killing MRSA infections in the body as well as disinfecting medical or
| + | |
− | sports equipment.
| + | |
− | </p>
| + | |
| | | |
− | <h2>References</h2>
| + | .container { |
− | <ol>
| + | padding-top: 100px; |
− | <li>
| + | display: flex; |
− | Staphylococcal infections [Internet]. Merck Manuals; [updated 2017 Sept; cited 2019 Jun 28].
| + | flex-direction: column; |
− | Available from:
| + | justify-content: flex-start; |
− | https://www.merckmanuals.com/professional/infectious-diseases/gram-positive-cocci/staphylococcal-infections
| + | } |
− | </a>
| + | |
− | </li>
| + | |
| | | |
− | <li>
| + | .affix { |
− | Staph infections can kill [Internet]. Centers for Disease Control and Prevention (US); [updated 2019 Mar 22; cited 2019 Jun 28].
| + | top:0; |
− | Available from: https://www.cdc.gov/vitalsigns/staph/index.html">https://www.cdc.gov/vitalsigns/staph/index.html</a>
| + | width: 182 px; |
− | </li>
| + | z-index: 9999 !important; |
| + | } |
| + | |
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| + | width: 181 px; |
| + | } |
| + | |
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| + | margin-left: 212px; |
| + | } |
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| + | } |
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| + | padding-left:7% |
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| + | background-color: white; |
| + | border: white; |
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| + | |
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| + | background-color: white; |
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| | | |
− | <li>
| + | .nav-pills li{ |
− | Hwang IY, Tan MH, Koh E, Ho CL, Poh CL, Chang MW. Reprogramming microbes to be pathogen-seeking killers. ACS Synth Biol. 2013;3(4):228-237.
| + | line-height: 1.5; |
− | <a href="https://doi.org/10.1021/sb400077j"></a>
| + | } |
− | </li>
| + | .dropdown li{ |
| | | |
− | <li>
| + | font-size: 13pt; |
− | Rutherford ST, Bassler, B. L. Bacterial quorum sensing: its role in virulence and possibilities for its control.
| + | line-height: 2.0 |
− | Cold Spring Harb Perspect Med. 2012;2(11).
| + | } |
− | </li>
| + | |
| | | |
− | <li>
| + | .body-background .background-text{ |
− | Tan L, Li SR, Jiang B, Hu, XM, Li S. Therapeutic targeting of the <i>Staphylococcus aureus</i> accessory gene regulator
| + | padding-top: 180px; |
− | (agr) system. Front Microbiol. 2018;9(55).
| + | text-align: center; |
− | </li>
| + | |
| | | |
− | <li>
| + | } |
− | Cheung AL, Zhang G. Global regulation of virulence determinants in <i>Staphylococcus aureus</i> by the SarA protein
| + | |
− | family. Front Biosci. 2002;7:1825-1842.
| + | |
− | </li>
| + | /**********************/ |
| + | /* 16. Footer */ |
| + | /**********************/ |
| + | .footer { |
| + | padding-bottom: 0.5rem; |
| + | } |
| | | |
− | <li>
| + | .footer .footer-col { |
− | Wang Y, Chen CL, Iijima M. Signaling mechanisms for chemotaxis. Dev Growth Differ. 2011;53(4):495-502.
| + | margin-bottom: 2.25rem; |
− | </li>
| + | } |
− |
| + | |
− | <li>
| + | |
− | Chi H, Holo H. Synergistic antimicrobial activity between the broad spectrum bacteriocin garvicin KS and nisin,
| + | |
− | farnesol, and polymyxin B against Gram-positive and Gram-negative bacteria. Curr Microbiol. 2018;75(3):272-277.
| + | |
− | </li>
| + | |
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− | <li>
| + | .footer h4 { |
− | Ovchinnikov KV, Chi H, Mehmeti I, Holo H, Nes IF, Diep, DB. Novel group of leaderless multipeptide
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− | bacteriocins from Gram-positive bacteria. Appl Environ Microbiol. 2016;82(17):5216-5224.
| + | } |
− | </li>
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− | <li>
| + | .footer .list-unstyled .fas { |
− | Han S, Machhi S, Berge M, Xi G, Linke T, Schoner R. Novel signal peptides improve
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− | the secretion of recombinant <i>Staphylococcus aureu</i>s alpha toxin H35L in <i>Escherichia coli</i>. AMB Expr. 2017;7(93).
| + | font-size: 0.9rem; |
− | </li>
| + | line-height: 1.375rem; |
| + | } |
| | | |
− | <li>
| + | .footer .list-unstyled .media-body { |
− | Lopez D, Vlamakis H, Kolter R. (2010). Biofilms. Cold Spring Harb Perspect Biol. 2010;2(7).
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− | </li>
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− | <li>
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− | Ciofu O, Rojo-Molinero E, Macia MD, Oliver A. (2017). Antibiotic treatment of biofilm infections. APMIS. 2017;125(4).
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− | Mathur H, Field D, Rea MC, Cotter PD, Hill C, Ross RP. (2018). Fighting biofilms with lantibiotics and other groups of
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− | bacteriocins. NPJ Biofilms Microbiomes. 2018;4.
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− | </li>
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− | </div> | + | |
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| + | .footer .fa-stack:hover .fa-stack-1x { |
| + | color: #fff; |
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| + | .footer .fa-stack:hover .fa-stack-2x { |
| + | color: #00a7bd; |
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| + | .footer .fa-stack a img{ |
| + | padding-left:10px ; |
| + | padding-right: 10px; |
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| + | background: url('https://static.igem.org/mediawiki/2019/f/fa/T--UNebraska-Lincoln--contact-background.jpeg') center center no-repeat; |
| + | } |
| + | /* Footer */ |
| + | .footer .footer-col { |
| + | width: 90%; |
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| + | .footer .footer-col.middle { |
| + | margin-right: auto; |
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| + | /* end of footer */ |
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| + | </style> |
| + | |
| + | <body> |
| + | <div class="container"> |
| + | <div class="body-background"> |
| + | <div class="background-text"> |
| + | <h1 style="color: white; |
| + | font-weight: bold; |
| + | font-size: 40pt;">Project Description</h1> |
| + | </div> |
| + | </div> |
| + | <div class="body-content" data-spy="scroll" data-target=".navbar" data-offset="50"> |
| + | |
| + | <div class="page-content"> |
| + | <div class="row affix-row" style="margin-left: 0; margin-right: 0;"> |
| + | <div class="col-xs-2" data-spy="affix" data-offset-top="197"> |
| + | <nav id="nav" class="navbar navbar-inverse" > |
| + | <div class="container-fluid"> |
| + | <div> |
| + | <div class="collapse navbar-collapse" id="myNavbar"> |
| + | <ul class="nav nav-pills flex-column"> |
| + | <li><a href="#section1">Problem</a></li> |
| + | <li><a href="#section2">Inspiration</a></li> |
| + | <li class="dropdown"> |
| + | <a class="dropdown-toggle" data-toggle="dropdown" href="#">Solution </a> |
| + | <ul class="dropdown"> |
| + | <li><a href="#section31">Sensing</a></li> |
| + | <li><a href="#section32">Motility</a></li> |
| + | <li><a href="#section33">Killing</a></li> |
| + | </ul> |
| + | </li> |
| + | <li><a href="#section4">Impact</a></li> |
| + | <li><a href="#section5">References</a></li> |
| + | |
| + | |
| + | </ul> |
| + | </div> |
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| + | </nav> |
| + | </div> |
| + | |
| + | <div class="col-xs-8"> |
| + | <div class="row"> |
| + | <div id="section1" class="col-xs-12"> |
| + | <h1>Problem</h1> |
| + | <p> |
| + | <i>Staphylococcus aureus</i> is a type of bacteria commonly found in hospitals, sports facilities, |
| + | and even the bodies of healthy individuals (1). As many as one third of the population carries |
| + | <i>S. aureus</i> in their nose, and about 20% of people carry <i>S. aureus</i> on the skin (1). While <i>S. aureus</i> |
| + | does not normally cause severe problems, it can cause infections of the skin, blood, and soft tissues, |
| + | with approximately 20,000 deaths reported in the United States in 2017 as a result of <i>S. aureus</i> infection (2). |
| + | Methicillin-resistant <i>Staphylococcus aureus</i>, or MRSA, is a potent strain of <i>S. aureus</i> that is resistant to |
| + | common antibiotic treatments (1). This resistance to conventional treatment makes MRSA infections difficult to |
| + | combat, turning <i>S. aureus</i> into a much more deadly pathogen. To overcome antibiotic resistance, the medical |
| + | community must find new ways to combat bacterial infection. |
| + | </p> |
| + | </div> |
| + | </div> |
| + | <div class="row"> |
| + | <div id="section2" class="col-xs-12"> |
| + | <h1>Inspiration</h1> |
| + | <p> |
| + | Our team was inspired by a 2013 paper by Hwang et al. titled “Reprogramming Microbes to be Pathogen-Seeking Killers” (3). |
| + | Hwang et al. engineered <i>E. coli</i> to detect and fight <i>Pseudomonas aeruginosa</i> infections using a seek-and-kill technique. |
| + | Their design is modular, which makes it possible to use their approach to target different bacteria. We found that the |
| + | rise of antibiotic resistant bacteria makes it increasingly vital to find new treatments, which inspired us to adapt the |
| + | system devised by Hwang et al. to target methicillin-resistant <i>Staphylococcus aureus</i>, or MRSA. |
| + | <p> |
| + | <img height=400px width=100% src="https://static.igem.org/mediawiki/2019/5/54/T--UNebraska-Lincoln--030.jpg" width="" alt="alt_text" title="image_tooltip"> |
| + | <p style="width:100%; text-align: center;"> |
| + | Our modified version of the system, designed to target and treat <i>Staphylococcus aureus</i>. |
| + | </p> |
| + | </p> |
| + | </div> |
| + | </div> |
| + | <div class="row"> |
| + | <div id="section31" class="col-xs-12"> |
| + | <h1>Sensing</h1> |
| + | <p> |
| + | Quorum sensing is a method of cell communication that uses small molecules to regulate gene expression (4). Gram-positive |
| + | and Gram-negative use different small molecules to accomplish quorum sensing; Gram-positive species use autoinducing peptides |
| + | (AIP) while Gram-negative species use acyl homoserine lactones (AHL) (4). Our target species, <i>Staphylococcus aureus</i>, |
| + | uses four forms of AIP in the accessory gene regulator (<i>agr</i>) quorum sensing system. In the <i>agr</i> system, the genes agrA and |
| + | agrC code for proteins that detect AIP produced by neighboring <i>S. aureus</i> and activate the P2 promoter in response (5). |
| + | </p> |
| + | <p> |
| + | Our project builds on BBa_K1022100, a BioBrick that combines AgrA and AgrC from the <i>agr</i> sensing system with green |
| + | fluorescent protein under a pBAD promoter. We found that the wild-type AgrA and AgrC proteins contain amino acids not |
| + | present in BBa_K1022100, and we aim to modify and potentially improve the existing part by introducing these missing |
| + | amino acids. The P2 promoter used in BBa_K1022100 is also missing base pairs found in the binding site region of the |
| + | wild-type P2 sequence. We plan to reintroduce these binding sites by using a more complete P2 promoter sequence to |
| + | improve GFP production in the original BioBrick. Lastly, SarA is a transcriptional activator found in <i>S. aureus</i> |
| + | that is believed to activate expression of genes in the <i>agr</i> system (6). We will introduce the SarA gene to further |
| + | improve the effectiveness of the <i>agr</i> system. |
| + | </p> |
| + | </div> |
| + | </div> |
| + | <div class="row"> |
| + | <div id="section32" class="col-xs-12"> |
| + | <h1>Motility</h1> |
| + | <p> |
| + | Chemotaxis is the movement of a cell towards or away from a chemical stimulus based on concentration, either from |
| + | high to low or from low to high (7). In our system, AIP will provide the chemical gradient necessary to move <i>E. coli</i> |
| + | in the direction of <i>S. aureus</i>. Chemotaxis is influenced by the post-translation modulation of the CheY and CheZ |
| + | proteins; however, there is an issue of potential overexpression that can lead to the inhibition of chemotaxis (3). |
| + | In order to combat this issue, we will be implementing a degron, a sequence of amino acids responsible for protein |
| + | degradation, to control CheZ expression (3). We will attach the YbaQ degron to CheZ’s C-terminus, much like the |
| + | application used by the Hwang et al. study in 2013 (3). To demonstrate the functionality of chemotaxis in our system, |
| + | we will first use a pBAD promoter to trigger chemotaxis. If successful, we will replace the pBAD promoter with a P2 |
| + | promoter which is activated by the <i>agr</i> system. This will ignite chemotaxis in the presence of AIP, moving the <i>E. coli</i> towards <i>S. aureus.</i> |
| + | </p></div> |
| + | </div> |
| + | <div class="row"> |
| + | <div id="section33" class="col-xs-12"> |
| + | <h1>Killing</h1> |
| + | <p> |
| + | Bacteriocins are small antimicrobial peptides (AMPs) produced by bacteria to kill or inhibit other bacteria. |
| + | Many AMPs are currently under study as potential alternatives to antibiotic treatment due to the rise of antibiotic |
| + | resistance. One such AMP is garvicin KS, a bacteriocin produced by <i>Lactococcus garvieae</i>, a bacterial species |
| + | found in raw milk. Garvicin KS is effective against <i>S. aureus</i> and other Gram-positive bacteria, and is more potent |
| + | than many other bacteriocins (8). Mature garvicin KS is composed of three polypeptides encoded by three genes: |
| + | GakA, GakB, and GakC (9). By placing these genes into an <i>E. coli</i> chassis, we plan to use <i>E. coli</i> to produce |
| + | garvicin KS. As <i>E. coli</i> is a Gram-negative bacterium, additional steps must be taken to ensure that the |
| + | garvicin KS peptides can be secreted from the cell. We have chosen a novel signal peptide first constructed |
| + | in a 2017 paper by Han et al. to assist with secretion of the garvicin KS peptides (10). This peptide tags |
| + | proteins for secretion by the Sec pathway, a pathway used by <i>E. coli</i> to secrete proteins into the periplasm |
| + | and outer membrane (10). |
| + | |
| + | </p> |
| + | |
| + | </div> |
| + | </div> <div class="row"> |
| + | <div id="section4" class="col-xs-12"> |
| + | <h1>Impact</h1> |
| + | <p> |
| + | Our system has the potential to be used both in vivo and in vitro to combat MRSA planktonic cells and biofilms. |
| + | Many bacteria produce biofilms, which are collections of cells attached to a surface and the extracellular matrix |
| + | that encases these cells (11). Biofilms provide protection to the bacteria within and are often resistant to |
| + | antibiotic treatment, which further compounds the issue of antibiotic resistance (12). One possible solution |
| + | is the use of antimicrobial peptides such as garvicin KS, which have been shown to be more effective towards |
| + | biofilms than traditional antibiotics (13). Our three module system first uses quorum sensing to detect AIP |
| + | produced by MRSA biofilms and planktonic cells. Detection of AIP simultaneously triggers chemotaxis and the |
| + | production of garvicin KS. The use of chemotaxis allows our <i>E. coli</i> to seek out and move towards biofilms and |
| + | planktonic cells, releasing garvicin KS near the source and maximizing effectiveness. Potential applications |
| + | of the system include detecting and killing MRSA infections in the body as well as disinfecting medical or |
| + | sports equipment. |
| + | </p> |
| + | </div> |
| + | </div> <div class="row"> |
| + | <div id="section5" class="col-xs-12"> |
| + | <h1>References</h1> |
| + | <ol> |
| + | <li> |
| + | Staphylococcal infections [Internet]. Merck Manuals; [updated 2017 Sept; cited 2019 Jun 28]. |
| + | Available from: |
| + | https://www.merckmanuals.com/professional/infectious-diseases/gram-positive-cocci/staphylococcal-infections |
| + | </a> |
| + | </li> |
| + | |
| + | <li> |
| + | Staph infections can kill [Internet]. Centers for Disease Control and Prevention (US); [updated 2019 Mar 22; cited 2019 Jun 28]. |
| + | Available from: https://www.cdc.gov/vitalsigns/staph/index.html">https://www.cdc.gov/vitalsigns/staph/index.html</a> |
| + | </li> |
| + | |
| + | <li> |
| + | Hwang IY, Tan MH, Koh E, Ho CL, Poh CL, Chang MW. Reprogramming microbes to be pathogen-seeking killers. ACS Synth Biol. 2013;3(4):228-237. |
| + | <a href="https://doi.org/10.1021/sb400077j"></a> |
| + | </li> |
| + | |
| + | <li> |
| + | Rutherford ST, Bassler, B. L. Bacterial quorum sensing: its role in virulence and possibilities for its control. |
| + | Cold Spring Harb Perspect Med. 2012;2(11). |
| + | </li> |
| + | |
| + | <li> |
| + | Tan L, Li SR, Jiang B, Hu, XM, Li S. Therapeutic targeting of the <i>Staphylococcus aureus</i> accessory gene regulator |
| + | (agr) system. Front Microbiol. 2018;9(55). |
| + | </li> |
| + | |
| + | <li> |
| + | Cheung AL, Zhang G. Global regulation of virulence determinants in <i>Staphylococcus aureus</i> by the SarA protein |
| + | family. Front Biosci. 2002;7:1825-1842. |
| + | </li> |
| + | |
| + | <li> |
| + | Wang Y, Chen CL, Iijima M. Signaling mechanisms for chemotaxis. Dev Growth Differ. 2011;53(4):495-502. |
| + | </li> |
| + | |
| + | <li> |
| + | Chi H, Holo H. Synergistic antimicrobial activity between the broad spectrum bacteriocin garvicin KS and nisin, |
| + | farnesol, and polymyxin B against Gram-positive and Gram-negative bacteria. Curr Microbiol. 2018;75(3):272-277. |
| + | </li> |
| + | |
| + | <li> |
| + | Ovchinnikov KV, Chi H, Mehmeti I, Holo H, Nes IF, Diep, DB. Novel group of leaderless multipeptide |
| + | bacteriocins from Gram-positive bacteria. Appl Environ Microbiol. 2016;82(17):5216-5224. |
| + | </li> |
| + | |
| + | <li> |
| + | Han S, Machhi S, Berge M, Xi G, Linke T, Schoner R. Novel signal peptides improve |
| + | the secretion of recombinant <i>Staphylococcus aureu</i>s alpha toxin H35L in <i>Escherichia coli</i>. AMB Expr. 2017;7(93). |
| + | </li> |
| + | |
| + | <li> |
| + | Lopez D, Vlamakis H, Kolter R. (2010). Biofilms. Cold Spring Harb Perspect Biol. 2010;2(7). |
| + | </li> |
| + | |
| + | <li> |
| + | Ciofu O, Rojo-Molinero E, Macia MD, Oliver A. (2017). Antibiotic treatment of biofilm infections. APMIS. 2017;125(4). |
| + | </li> |
| + | |
| + | <li> |
| + | Mathur H, Field D, Rea MC, Cotter PD, Hill C, Ross RP. (2018). Fighting biofilms with lantibiotics and other groups of |
| + | bacteriocins. NPJ Biofilms Microbiomes. 2018;4. |
| + | </li> |
| + | </ol> |
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