Severity: Warning
Message: file_get_contents(https://...@gmail.com&api_key=61f08fa0b96a73de8c900d749fcb997acc09): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
Filename: helpers/my_audit_helper.php
Line Number: 143
Backtrace:
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 143
Function: file_get_contents
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 209
Function: simplexml_load_file_from_url
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 994
Function: getPubMedXML
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 3134
Function: GetPubMedArticleOutput_2016
File: /var/www/html/application/controllers/Detail.php
Line: 574
Function: pubMedSearch_Global
File: /var/www/html/application/controllers/Detail.php
Line: 488
Function: pubMedGetRelatedKeyword
File: /var/www/html/index.php
Line: 316
Function: require_once
Staphylococcus aureus is a prominent nosocomial pathogen that causes several life-threatening diseases, such as pneumonia and bacteremia. S. aureus modulates the expression of its arsenal of virulence factors through sensing and integrating responses to environmental signals. The (accessory gene regulator) quorum sensing (QS) system is a major regulator of virulence phenotypes in S. aureus. There are four specificity groups each with a different autoinducer peptide sequence encoded by the gene. Although is critical for the expression of many toxins, paradoxically, S. aureus strains often have nonfunctional activity due to loss-of-function mutations in the four-gene operon. To understand patterns in variability across S. aureus, we undertook a species-wide genomic investigation. We developed a software tool (AgrVATE; https://github.com/VishnuRaghuram94/AgrVATE) for typing and detecting frameshift mutations in the operon. In an analysis of over 40,000 S. aureus genomes, we showed a close association between type and S. aureus clonal complex. We also found a strong linkage between alleles (encoding the peptidase, autoinducing peptide itself, and peptide sensor, respectively) but not (encoding the response regulator). More than 5% of the genomes were found to have frameshift mutations in the operon. While 52% of these frameshifts occurred only once in the entire species, we observed cases where the recurring mutations evolved convergently across different clonal lineages with no evidence of long-term phylogenetic transmission, suggesting that strains with frameshifts were evolutionarily short-lived. Overall, genomic analysis of operon suggests evolution through multiple processes with functional consequences that are not fully understood. Staphylococcus aureus is a globally pervasive pathogen that produces a plethora of toxic molecules that can harm host immune cells. Production of these toxins is mainly controlled by an active quorum-sensing system, which senses and responds to bacterial cell density. However, there are many reports of S. aureus strains with genetic changes leading to impaired activity that are often found during chronic bloodstream infections and may be associated with increased disease severity. We developed an open-source software called AgrVATE to type systems and identify mutations. We used AgrVATE for a species-wide genomic survey of S. aureus, finding that more than 5% of strains in the public database had nonfunctional systems. We also provided new insights into the evolution of these genetic mutations in the system. Overall, this study contributes to our understanding of a common but relatively understudied means of virulence regulation in S. aureus.
Download full-text PDF |
Source |
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8768832 | PMC |
http://dx.doi.org/10.1128/spectrum.01334-21 | DOI Listing |
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