<i>Staphylococcus aureus</i> (<i>S.aureus</i>) is a common pathogen that the enterotoxins released by it is a sever pathogenic factor of food poisoning cases. <i>S.aureus</i> doesn’t need restricted conditions to grow; It has great resistance to arid, heated and saliferous conditions, therefore spreading and surviving widely in the environment around people. <i>S.aureus</i> is ubiquitous in nature which can be found in air, water, dust and human and animal’s waste. As a result, People can easily be exposed to <i>S.aureus</i> and get infected. Nowadays, <i>S.aureus</i> has become a worldly health problem. Reported by the U.S. Centers of Disease Control, about 25% food poisoning cases are caused by <i>S.aureus</i> infection in China, about 33% in the U.S., and even about 45% in Canada. As people infected by <i>S.aureus</i>, it will cause detrimental diseases as pneumonia, pericarditis, sepsis and death. In the hospital or communities, people catch <i>S.aureus</i> through contact infection and the morbidity rate in a developed country is between 100,000 to 300,000 people each year. According to data from the Emerging Infections program (EIP) and Cerner Electronic Health Record databases, 19,832 associated deaths occurred in an estimated 119,247 <i>S.aureus</i> bloodstream infections in 2017. To understand the spreading range of <i>S.aureus</i>, we construct the following experiments.
<i>Staphylococcus aureus</i> (<i>S.aureus</i>) is a common pathogen that the enterotoxins released by it is a sever pathogenic factor of food poisoning cases. <i>S.aureus</i> doesn’t need restricted conditions to grow; It has great resistance to arid, heated and saliferous conditions, therefore spreading and surviving widely in the environment around people. <i>S.aureus</i> is ubiquitous in nature which can be found in air, water, dust and human and animal’s waste. As a result, People can easily be exposed to <i>S.aureus</i> and get infected. Nowadays, <i>S.aureus</i> has become a worldly health problem. Reported by the U.S. Centers of Disease Control, about 25% food poisoning cases are caused by <i>S.aureus</i> infection in China, about 33% in the U.S., and even about 45% in Canada. As people infected by <i>S.aureus</i>, it will cause detrimental diseases as pneumonia, pericarditis, sepsis and death. In the hospital or communities, people catch <i>S.aureus</i> through contact infection and the morbidity rate in a developed country is between 100,000 to 300,000 people each year. According to data from the Emerging Infections program (EIP) and Cerner Electronic Health Record databases, 19,832 associated deaths occurred in an estimated 119,247 <i>S.aureus</i> bloodstream infections in 2017. To understand the spreading range of <i>S.aureus</i>, we construct the following experiments.
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<h2>Theory </h2>
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<b>Why <i>S.aureus</i> can cause disease and the mechanism?</b>
<b>Why <i>S.aureus</i> can cause disease and the mechanism?</b>
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<i>S.aureus</i>, one of the most widespread pathogens, causes mainly pneumonia and other respiratory infections. The cases of patients getting infected by <i>S.aureus</i> can reach to a unbelievable number in America, which represents a huge public health burden. Since <i>S.aureus</i> isolates appear to be occasionally antibiotic resistant, the problems of infecting <i>S.aureus</i> prove to be especially important, among which the methicillin-resistant <i>S.aureus</i> (MRSA) receives more attention clinically. Compared with methicillin-sensitive <i>S.aureus</i> (MSSA), infections by MRSA are accompanied by increases in death rate, morbidity, and hospital stay.
<i>S.aureus</i>, one of the most widespread pathogens, causes mainly pneumonia and other respiratory infections. The cases of patients getting infected by <i>S.aureus</i> can reach to a unbelievable number in America, which represents a huge public health burden. Since <i>S.aureus</i> isolates appear to be occasionally antibiotic resistant, the problems of infecting <i>S.aureus</i> prove to be especially important, among which the methicillin-resistant <i>S.aureus</i> (MRSA) receives more attention clinically. Compared with methicillin-sensitive <i>S.aureus</i> (MSSA), infections by MRSA are accompanied by increases in death rate, morbidity, and hospital stay.
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The virulence factors of <i>S.aureus</i> often encode on the accessory genome of the pathogens, which differs from the code genome that encodes “housekeeping” functions. The accessory genome involves mobile genetic elements (MGE), such as plasmids, transposons, sequences and pathogenicity islands. Apart from virulence factors, it also contains antibiotic resistant determinants. The different MGE take the responsibility for coding different poisons, including TSST-1 or the food poisoning toxins.
The virulence factors of <i>S.aureus</i> often encode on the accessory genome of the pathogens, which differs from the code genome that encodes “housekeeping” functions. The accessory genome involves mobile genetic elements (MGE), such as plasmids, transposons, sequences and pathogenicity islands. Apart from virulence factors, it also contains antibiotic resistant determinants. The different MGE take the responsibility for coding different poisons, including TSST-1 or the food poisoning toxins.
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<b>Quorum sensing system in <i>S.aureus</i></b>
<b>Quorum sensing system in <i>S.aureus</i></b>
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The regulation of virulence in <i>S.aureus</i> is highly complicated, consisting of large amounts of regulatory systems and parts, so that because of the size of the article, we only depict the most important ones. <i>S.aureus</i> virulence determinants is regulated by a large range of influences, including regulations by local-specific regulations, such as the icaR gene that is connected to ica operator, is subject to many impacts. Here, we just choose some specific condition. Apart from Agr, the exact model of the systems is hard to predict till now. Agr, or accessory gene regulator, is a quorum-sensing system that levels up the contents of many poisons and virulence determinants when the density of cells raise to a certain amount. Within a phagosome, factors controlled by Agr are expressed possibly by “diffusion sensing” to activates the quorum-sensing system. As predicted, inflammation caused by <i>S.aureus</i> are led by Agr mutants in many animal infection models. Because of the enlarging of the biofilm formed by Agr mutants, the cells turn to have a stronger resistance towards neutrophil attacks, leading to biofilm-related infections.
The regulation of virulence in <i>S.aureus</i> is highly complicated, consisting of large amounts of regulatory systems and parts, so that because of the size of the article, we only depict the most important ones. <i>S.aureus</i> virulence determinants is regulated by a large range of influences, including regulations by local-specific regulations, such as the icaR gene that is connected to ica operator, is subject to many impacts. Here, we just choose some specific condition. Apart from Agr, the exact model of the systems is hard to predict till now. Agr, or accessory gene regulator, is a quorum-sensing system that levels up the contents of many poisons and virulence determinants when the density of cells raise to a certain amount. Within a phagosome, factors controlled by Agr are expressed possibly by “diffusion sensing” to activates the quorum-sensing system. As predicted, inflammation caused by <i>S.aureus</i> are led by Agr mutants in many animal infection models. Because of the enlarging of the biofilm formed by Agr mutants, the cells turn to have a stronger resistance towards neutrophil attacks, leading to biofilm-related infections.
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<h2>Design</h2>
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<b>Why we choose TurboID to block QS in <i>S.aureus</i>? </b>
<b>Why we choose TurboID to block QS in <i>S.aureus</i>? </b>
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Before talking about TurboID itself, we are necessary to know that biotin has already been verified to be useful in the process of blocking surface receptors. Here is a concrete example, cited the information from Macromolecular Research, Vol. 15, No. 7, pp 646-655 (2007), the biotin-conjugated PEG/PCL block copolymer itself evidenced no significant adverse effects on human cells regardless of the cell types. Apparently, as TurboID is also a biotin, we can briefly conclude that TurboID is useful no matter what.
