Difference between revisions of "Team:ETH Zurich/core/human-practices"

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  <img src="https://static.igem.org/mediawiki/2019/b/b5/T--ETH_Zurich--AntibioticsResistance.svg" alt="antibioticsresistance" class="hp-icon">
 
  <img src="https://static.igem.org/mediawiki/2019/b/b5/T--ETH_Zurich--AntibioticsResistance.svg" alt="antibioticsresistance" class="hp-icon">
 
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           <p>
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           Antibiotic resistant bacteria affect individuals independent of age, socio-economic status and country of residence and thus pose one of the biggest threats to global health today. It is an inevitable evolutionary response to antimicrobial usage. Susceptible pathogens are being replaced by more resistant variants by the process of natural selection [2]. However, despite the fact that this is a natural process, it is greatly accelerated by the misuse of antibiotics in humans and livestock. In a US-based study focusing on the usage of antibiotics in ambulatory care visits, more than 30% of cases showed unnecessary or inappropriate antibiotics prescriptions [3]. Furthermore, many antibiotics relevant for human medicine are extensively being used in animal agriculture. They are routinely fed to animals to proactively prevent infections [4].
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           Antibiotic resistant bacteria affect individuals independent of age, socio-economic status and country of residence and thus pose one of the biggest threats to global health today. It is an inevitable evolutionary response to antimicrobial usage. Susceptible pathogens are being replaced by more resistant variants by the process of natural selection [2]. However, despite the fact that this is a natural process, it is greatly accelerated by the misuse of antibiotics in humans and livestock [3][4].
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           An increasing number of infections such as pneumonia, tuberculosis and food borne diseases are becoming harder or even impossible to treat as antibiotics become less effective against particular bacterial strains. Standard procedures such as organ transplantations, chemotherapy and routine surgeries like caesarean sections will involve more risk in the future if no alternative methods are developed. The length of hospitalizations will increase as a consequence, leading to higher medical costs and potentially increased mortality rates [1]. Therefore, the treatment of multi-drug resistant bacteria is highly relevant.
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           An increasing number of infections such as pneumonia, tuberculosis and food borne diseases are becoming harder to treat as antibiotics become less effective against particular bacterial strains. Standard procedures such as organ transplantations, chemotherapy and routine surgeries like caesarean sections will involve more risk in the future if no alternative methods are developed. The length of hospitalizations will increase as a consequence, leading to higher medical costs and potentially increased mortality rates [1]. Therefore, the treatment of multi-drug resistant bacteria is highly relevant.
 
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           <p>
 
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           After injecting their DNA into a host, phages either multiply and induce lysis of the host cell or they are stabilized as prophages either integrated into the host chromosome (temperate phages) or as a free plasmid molecule. Temperate phages can mediate horizontal gene transfer that occurs in bacteria through transduction. Transduction is a mechanism by which a segment of the bacterial genome is inserted in a newly formed viral particle instead of the viral genome which can therefore be transferred to other bacteria and can recombine with the host’s genome by homologous recombination. From a biosafety point of view, the introduction of new genetic material from a recombinant viral particle into the bacterial gene pool may have positive, negative or neutral outcomes depending on the genetic marker introduced. Examples for negative outcomes include the transduction of antibiotic resistance genes or pathogenicity islands [1]. <br>
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           After injecting their DNA into a host, phages either multiply and induce lysis of the host cell or they are stabilized as prophages either integrated into the host chromosome (temperate phages) or as a free plasmid molecule. Temperate phages can mediate horizontal gene transfer that occurs in bacteria through transduction. Transduction is a mechanism by which a segment of the bacterial genome is inserted in a newly formed viral particle instead of the viral genome which can therefore be transferred to other bacteria and can recombine with the host’s genome by homologous recombination. From a biosafety point of view, the introduction of new genetic material from a recombinant viral particle into the bacterial gene pool may have positive, negative or neutral outcomes depending on the genetic marker introduced [1]. <br>
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           The survival of bacteriophages outside a host is extremely variable. It depends on the nature of the phage itself and is further influenced by the surrounding environmental conditions. Even if free phages can survive a rather long time in the environment, they need to infect susceptible bacterial hosts to replicate and propagate themselves. Many phages are known to be highly specific for their receptors and are therefore characterized by a narrow host range. However, some phages that are able to infect a large range of bacterial species have also been identified. These broad-host-range phages may promote genetic diversity and genetic exchange among a wider range of bacterial populations. Determination of the host range, virulence, resistance to environmental factors or the potential for gene transfer of the manipulated bacteriophage is therefore an important step in the risk assessment process to evaluate the probability of the phage’s propagation in a particular environment and its potential role in global gene transfer [1]. <br>
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           The survival of bacteriophages outside a host depends on the nature of the phage itself and is further influenced by the surrounding environmental conditions. Even if free phages can survive a rather long time in the environment, they need to infect susceptible bacterial hosts to replicate and propagate themselves. Many phages are known to be highly specific for their receptors and are therefore characterized by a narrow host range. However, some phages that are able to infect a large range of bacterial species have also been identified. These broad-host-range phages may promote genetic diversity and genetic exchange among a wider range of bacterial populations. Determination of the host range, virulence, resistance to environmental factors or the potential for gene transfer of the manipulated bacteriophage is therefore an important step in the risk assessment process to evaluate the probability of the phage’s propagation in a particular environment and its potential role in global gene transfer [1]. <br>
 
           We have chosen to work with bacteriophage T7, as it is a well-characterized lytic phage, which is considered to have low potential for transduction and cannot alter the genotype of its host. Furthermore, it has a narrow host range, which limits the risk of dissemination and is classified as biosafety level 1.
 
           We have chosen to work with bacteriophage T7, as it is a well-characterized lytic phage, which is considered to have low potential for transduction and cannot alter the genotype of its host. Furthermore, it has a narrow host range, which limits the risk of dissemination and is classified as biosafety level 1.
 
           </p>
 
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Revision as of 13:36, 3 September 2019

Human Practices

Human Practices is a method to ensure that our project is responsible and good for the world. To achieve this, we first brainstormed on globally relevant topics and decided to work on antibiotics resistance with phage therapy as the toolkit to do so. Secondly, we brainstormed societal concerns that are linked to our project, whereas we identified clinical application, patient safety, biosafety and regulatory process as significant issues to consider. Next, we met with stakeholders from the clinic and experts in safety and regulations to discuss our project. Finally, we integrated all our gained knowledge to improve our project. Furthermore, we used our platform to inform the public about phage therapy and synthetic biology in general. 

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