Severity: Warning
Message: file_get_contents(https://...@pubfacts.com&api_key=b8daa3ad693db53b1410957c26c9a51b4908&a=1): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
Filename: helpers/my_audit_helper.php
Line Number: 176
Backtrace:
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 176
Function: file_get_contents
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 250
Function: simplexml_load_file_from_url
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 1034
Function: getPubMedXML
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 3152
Function: GetPubMedArticleOutput_2016
File: /var/www/html/application/controllers/Detail.php
Line: 575
Function: pubMedSearch_Global
File: /var/www/html/application/controllers/Detail.php
Line: 489
Function: pubMedGetRelatedKeyword
File: /var/www/html/index.php
Line: 316
Function: require_once
Bacterial infection is a major challenge to human health. Although various potent antibiotics have emerged in recent decades, current challenges arise from the increasing number of multi-drug-resistant species. Infections associated with implants represent a particular challenge because they are usually diagnosed at an advanced stage and are difficult to treat with antibiotics owing to the formation of protective biofilms. In this study, we designed and explored a synthetic biology-inspired cell-based biosensor/actor for the detection and counteraction of bacterial infections. The system is generic, as it senses diverse types of infections and acts by enhancing the endogenous immune system. This strategy is based on genetically engineered sensor/actor cells that can sense type I interferons (IFNs), which are released by immune cells at the early stages of infection. IFN signalling activates a synthetic circuit to induce reporter genes with a sensitivity of only 5 pg mlof IFN and leads to a therapeutic protein output of 100 ng ml, resulting in theranostic cells that can visualize and fight infections. Robustness and resilience were achieved by implementing a positive feedback loop. We showed that diverse gram-positive and gram-negative implant-associated pathogenic bacteria activate the cascade in co-culture systems in a dose-dependent manner. Finally, we showed that this system can be used to secrete chemoattractants that facilitate the infiltration of immune cells in response to bacterial triggers. Together, the system is not only universal to bacterial infections, but also hypersensitive, allowing the sensing of infections at initial stages.
Download full-text PDF |
Source |
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http://dx.doi.org/10.1088/1758-5090/ad8bf4 | DOI Listing |
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